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From articles published in Journal of Pathology and Translational Medicine during the past two years (2021 ~ ).

Review
Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
J Pathol Transl Med. 2021;55(3):181-191.   Published online May 11, 2021
DOI: https://doi.org/10.4132/jptm.2021.03.23
  • 3,437 View
  • 226 Download
  • 7 Citations
AbstractAbstract PDF
Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

Citations

Citations to this article as recorded by  
  • FACILITATE: A real-world, multicenter, prospective study investigating the utility of a rapid, fully automated real-time PCR assay versus local reference methods for detecting epidermal growth factor receptor variants in NSCLC
    Anke Behnke, Anne Cayre, Giovanna De Maglio, Giuseppe Giannini, Lionel Habran, Marina Tarsitano, Massimiliano Chetta, David Cappellen, Alexandra Lespagnol, Cecile Le Naoures, Gabriella Massazza, Annarita Destro, Irina Bonzheim, Achim Rau, Achim Battmann,
    Pathology and Oncology Research.2023;[Epub]     CrossRef
  • Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics
    Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim
    Diagnostics.2022; 12(2): 326.     CrossRef
  • Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics
    Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
    Diagnostics.2022; 12(5): 1102.     CrossRef
  • Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
    Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
    Journal of Pathology and Translational Medicine.2022; 56(5): 249.     CrossRef
  • Biomarker testing of cytology specimens in personalized medicine for lung cancer patients
    Hyojin Kim, Jin-Haeng Chung
    Journal of Pathology and Translational Medicine.2022; 56(6): 326.     CrossRef
  • Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
    Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
    Journal of Pathology and Translational Medicine.2022; 56(6): 334.     CrossRef
  • Lung Cancer in Korea
    Sehhoon Park, Chang-Min Choi, Seung-Sik Hwang, Yoon-La Choi, Hyae Young Kim, Young-Chul Kim, Young Tae Kim, Ho Yun Lee, Si Yeol Song, Myung-Ju Ahn
    Journal of Thoracic Oncology.2021; 16(12): 1988.     CrossRef
Case Study
Adenocarcinoma of the minor salivary gland with concurrent MAML2 and EWSR1 alterations
Sangjoon Choi, Junhun Cho, Seung Eun Lee, Chung-Hwan Baek, Yi-Kyung Kim, Hyung-Jin Kim, Young Hyeh Ko
J Pathol Transl Med. 2021;55(2):132-138.   Published online January 22, 2021
DOI: https://doi.org/10.4132/jptm.2020.12.11
  • 2,240 View
  • 90 Download
  • 6 Citations
AbstractAbstract PDF
Salivary gland tumors are histologically diverse, and each entity has distinctive histopathological and molecular features. We report two cases of salivary gland tumors with unique histological and molecular findings, which have not been documented previously. The tumors were located in the base of the tongue in both patients. Most tumor cells were arranged in cords and nests, giving a trabecularlike appearance. Focally, glandular structures with intraluminal mucin and perivascular pseudorosette-like configurations were identified. Tumor cells had eosinophilic to clear cytoplasm, and showed mild nuclear atypia. They were positive for pancytokeratin and negative for S-100, p63, c-KIT, androgen receptor, and neuroendocrine markers. Multiple foci of capsular or lymphovascular invasion were identified, but the Ki-67 labeling index was low (< 5%). Fluorescence in situ hybridization revealed concurrent alterations of MAML2 and EWSR1 gene. Further investigations with a larger number of cases with similar histological and molecular features will accurately classify this tumor.

Citations

Citations to this article as recorded by  
  • Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics
    Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim
    Diagnostics.2022; 12(2): 326.     CrossRef
  • The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls
    Kanwalpreet Kaur, Shailee Mehta, Sangita Vanik, Priti Trivedi, Nirmalya Banerjee, Harsh Dhar, Sourav Datta, Subhadeep Karanjai
    European Archives of Oto-Rhino-Laryngology.2022; 279(8): 3769.     CrossRef
  • Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics
    Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
    Diagnostics.2022; 12(5): 1102.     CrossRef
  • Endometrioid Carcinomas of the Ovaries and Endometrium Involving Endocervical Polyps: Comprehensive Clinicopathological Analyses
    Jihee Sohn, Yurimi Lee, Hyun-Soo Kim
    Diagnostics.2022; 12(10): 2339.     CrossRef
  • Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma
    Sujin Park, Go Eun Bae, Jiyoung Kim, Hyun-Soo Kim
    Diagnostics.2021; 11(8): 1450.     CrossRef
  • Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors
    Hyunjin Kim, Kiyong Na, Go Eun Bae, Hyun-Soo Kim
    Diagnostics.2021; 11(11): 2042.     CrossRef
Review
Palmar and plantar fibromatosis: a review
Brian D. Stewart, Alessandra F. Nascimento
J Pathol Transl Med. 2021;55(4):265-270.   Published online July 7, 2021
DOI: https://doi.org/10.4132/jptm.2021.06.14
  • 3,419 View
  • 187 Download
  • 4 Citations
AbstractAbstract PDF
Palmar fibromatosis (Dupuytren disease/contracture) is the most common type of fibromatosis, defined as a benign proliferation of fibroblasts and myofibroblasts. The disease process is most common in white, middle-aged and older men occurring at the distal palmar crease leading to nodules and contracture, which in many cases recur after surgical treatment. In a similar process, plantar fibromatosis (Ledderhose disease) is a proliferation of fibroblasts and myofibroblasts on the plantar aponeurosis of mostly middle-aged patients that may lead to painful nodules but usually does not lead to contracture. Both processes are histologically similar, composed of a bland cellular proliferation of spindle cells with a bluish appearance and with a variable amount of background collagen, depending on the age of the lesion. The etiology of both lesions is still uncertain, while treatment ranges from observation to surgery, with some pharmacologic agents being investigated with mixed success. In this paper we provide an overview of both processes with regards to clinical and radiologic findings, pathophysiology, diagnosis, treatment, and prognosis.

Citations

Citations to this article as recorded by  
  • Prevalence of and Risk Factors for Adhesive Capsulitis of the Shoulder in Older Adults from Germany
    Louis Jacob, Razak M. Gyasi, Ai Koyanagi, Josep Maria Haro, Lee Smith, Karel Kostev
    Journal of Clinical Medicine.2023; 12(2): 669.     CrossRef
  • Comorbid Medical Issues in X-Linked Ichthyosis
    Lucija Brcic, Georgina H. Wren, Jack F.G. Underwood, George Kirov, William Davies
    JID Innovations.2022; 2(3): 100109.     CrossRef
  • The deep fascia and its role in chronic pain and pathological conditions: A review
    Flemming Kondrup, Nathaly Gaudreault, Gabriel Venne
    Clinical Anatomy.2022; 35(5): 649.     CrossRef
  • Pacinian Corpuscles as a Diagnostic Clue of Ledderhose Disease—A Case Report and Mapping of Pacinian Corpuscles of the Sole
    Jorge Feito, Ruth Esteban, María Lourdes García-Martínez, Francisco J. García-Alonso, Raquel Rodríguez-Martín, María Belén Rivas-Marcos, Juan L. Cobo, Benjamín Martín-Biedma, Manuel Lahoz, José A. Vega
    Diagnostics.2022; 12(7): 1705.     CrossRef
Original Articles
Clinicopathologic features of cutaneous metastases from internal malignancies
Hyeong Mok Kwon, Gyu Yeong Kim, Dong Hoon Shin, Young Kyung Bae
J Pathol Transl Med. 2021;55(4):289-297.   Published online July 7, 2021
DOI: https://doi.org/10.4132/jptm.2021.05.24
  • 2,619 View
  • 101 Download
  • 4 Citations
AbstractAbstract PDFSupplementary Material
Background
Cutaneous metastasis (CM) is the spread of cancer cells from a primary site to the skin and is rarely the first sign of silent cancer. We investigated the clinicopathological characteristics of CM from internal malignancies in Korean patients treated at our institution over 20 years.
Methods
The clinicopathological findings of 112 patients (62 females, 50 males) with CM diagnosed at Yeungnam University Hospital between 2000 and 2020 were retrospectively reviewed.
Results
Mean patient age was 58.6 years (range, 26 to 87 years), and the most common primary cancer site was breast (74.2%) in women and lung (36.0%) in men. Ninety-six patients (85.7%) presented with CM after primary tumor diagnosis. CM from the lung or biliary tract usually occurred within 2 years of primary tumor diagnosis, whereas metastases from the breast and kidney occurred several years later. The chest, abdomen, and scalp were common sites of CM. Breast cancer usually metastasized to chest skin, while gastrointestinal tract cancers commonly metastasized to the abdomen. The scalp was a common location for CM from various tumors. The most common dermatologic presentations were nodules and masses. Immunohistochemical studies helped identify underlying malignancies when primary tumors were unknown.
Conclusions
The relative frequency of CM parallels the overall incidence of primary malignant tumors, and CMs usually occur at anatomic sites close to the primary tumor. CM can be diagnosed based on clinical, radiological, and histological features; however, immunohistochemical study is required in some cases.

Citations

Citations to this article as recorded by  
  • Pigmented epidermotropic breast cancer metastases: A rare variant with a particularly unusual feature
    Juan Torre‐Castro, Cristina Moya‐Martínez, Lara Haya‐Martínez, María Dolores Mendoza‐Cembranos, Itziar Eraña‐Tomás, Luis Requena
    Journal of Cutaneous Pathology.2022; 49(1): 99.     CrossRef
  • Skin metastases in the clinical and dermoscopic aspects
    Grazyna Kamińska-Winciorek, Aleksandra Pilśniak, Wojciech Piskorski, Jerzy Wydmański
    Seminars in Oncology.2022; 49(2): 160.     CrossRef
  • Nonbrain metastases seen on magnetic resonance imaging during metastatic brain tumor screening
    Mio Sakai, Nobuo Kashiwagi, Katsuyuki Nakanishi, Noboru Maeda, Yasuhiro Nakaya, Junichiro Tanaka, Shinichiro Watanabe, Hidenari Hongyo, Yu Tanaka, Sawaka Yamada, Atsushi Kawata, Sou Toda, Koji Takano, Hideyuki Arita, Noriyuki Tomiyama
    Japanese Journal of Radiology.2022;[Epub]     CrossRef
  • Dermoscopy and novel non invasive imaging of Cutaneous Metastases
    Dimitrios Alexandris, Nektarios Alevizopoulos, Leonidas Marinos, Charikleia Gakiopoulou
    Advances in Cancer Biology - Metastasis.2022; 6: 100078.     CrossRef
Potential of AKT2 expression as a predictor of lymph-node metastasis in invasive breast carcinoma of no special type
Primariadewi Rustamadji, Elvan Wiyarta, Kristina Anna Bethania, Kusmardi Kusmardi
J Pathol Transl Med. 2021;55(4):271-278.   Published online June 14, 2021
DOI: https://doi.org/10.4132/jptm.2021.04.26
  • 2,035 View
  • 120 Download
  • 4 Citations
AbstractAbstract PDF
Background
Invasive breast carcinoma of no special type (IBC-NST) is the most common type of breast cancer and mainly causes regional lymph-node metastasis (LNM). We investigated the potential for AKT2 expression as a predictive biomarker for LNM in IBC-NST.
Methods
Forty-eight paraffin blocks containing IBC-NST primary tumors were divided into two groups based on presence or absence of LNM. Age, tumor grade, tumor size, lymphovascular invasion (LVI), and AKT expression were assessed. AKT2 expression was assessed based on immunohistochemical staining, while other data were collected from archives.
Results
Multiple logistic regression results showed that AKT2 expression and LVI were significantly associated with LNM (odds ratio [OR], 5.32; 95% confidence interval [CI], 1.42 to 19.93 and OR, 4.46; 95% CI, 1.17 to 16.97, respectively). AKT2 expression was able to discriminate against LNM (area under the receiver operating characteristic, 0.799 ± 0.063; 95% CI, 0.676 to 0.921) at an H-score cutoff of 104.62 (83.3% sensitivity, 62.5% specificity).
Conclusions
AKT2 expression has potential as a predictor of LNM in IBC-NST. The H-score cutoff for AKT2 expression can be used as a classification guide in future studies.

Citations

Citations to this article as recorded by  
  • Exploring the Expression of Survivin on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma
    Primariadewi Rustamadji, Elvan Wiyarta, Ineke Anggreani
    Open Access Macedonian Journal of Medical Sciences.2022; 10(B): 1440.     CrossRef
  • Effect of Omega-3-Rich Fish Oil on TNF-  Expression in Mice's Colonic Tissue Induced with Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS)
    Elvan Wiyarta, Kusmardi Kusmardi, Yurnadi Hanafi Midoen
    Research Journal of Pharmacy and Technology.2022; : 3179.     CrossRef
  • The potential of lunasin extract for the prevention of breast cancer progression by upregulating E-Cadherin and inhibiting ICAM-1
    Kusmardi Kusmardi, Elvan Wiyarta, Numlil Khaira Rusdi, Andi Muh. Maulana, Ari Estuningtyas, Hadi Sunaryo
    F1000Research.2021; 10: 902.     CrossRef
  • CD44 Variant Exon 6 Isoform Expression as a Potential Predictor of Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type
    Primariadewi Rustamadji, Elvan Wiyarta, Kristina A. Bethania, Rakesh Sathish Nair
    International Journal of Breast Cancer.2021; 2021: 1.     CrossRef
Reviews
Non-conventional dysplastic subtypes in inflammatory bowel disease: a review of their diagnostic characteristics and potential clinical implications
Won-Tak Choi
J Pathol Transl Med. 2021;55(2):83-93.   Published online March 9, 2021
DOI: https://doi.org/10.4132/jptm.2021.02.17
  • 2,908 View
  • 209 Download
  • 4 Citations
AbstractAbstract PDF
The early detection and grading of dysplasia is the current standard of care to minimize mortality from colorectal cancer (CRC) in patients with inflammatory bowel disease. With the development of advanced endoscopic resection techniques, colectomy is now reserved for patients with invisible/flat dysplasia (either high-grade [HGD] or multifocal low-grade dysplasia) or endoscopically unresectable lesions. Although most pathologists are familiar with the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, an increasing number of diagnostic material has led to the recognition of several different morphologic patterns of epithelial dysplasia. The term “non-conventional” dysplasia has been coined to describe these changes, but to date, the recognition and full appreciation of these novel forms of dysplasia by practicing pathologists is uneven. The recognition of these non-conventional subtypes is becoming increasingly important, as some of them appear to have a higher risk of developing HGD or CRC than conventional dysplasia or sporadic adenomas. This review describes the morphologic characteristics of all seven non-conventional subtypes that have been reported to date as well as our current understanding of their clinicopathologic and molecular features that distinguish them from conventional dysplasia or sporadic adenomas.

Citations

Citations to this article as recorded by  
  • And the story goes on: non-conventional dysplasia of the colorectum
    Lavisha S. Punjabi, Yi Neng Lai, Anjula Thomas
    Journal of Pathology and Translational Medicine.2022; 56(2): 109.     CrossRef
  • Clinicopathologic features of undetected dysplasia found in total colectomy or proctocolectomy specimens of patients with inflammatory bowel disease
    Dorukhan Bahceci, Gregory Y Lauwers, Won‐Tak Choi
    Histopathology.2022; 81(2): 183.     CrossRef
  • Increased Risk of Non-conventional and Invisible Dysplasias in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease
    Ruth Zhang, Gregory Y Lauwers, Won-Tak Choi
    Journal of Crohn's and Colitis.2022; 16(12): 1825.     CrossRef
  • Increased histologic inflammation is an independent risk factor for nonconventional dysplasia in ulcerative colitis
    Eric D. Nguyen, Dongliang Wang, Gregory Y. Lauwers, Won‐Tak Choi
    Histopathology.2022; 81(5): 644.     CrossRef
Imaging features of breast cancer molecular subtypes: state of the art
Nariya Cho
J Pathol Transl Med. 2021;55(1):16-25.   Published online November 9, 2020
DOI: https://doi.org/10.4132/jptm.2020.09.03
  • 46,164 View
  • 239 Download
  • 4 Citations
AbstractAbstract PDF
Characterization of breast cancer molecular subtypes has been the standard of care for breast cancer management. We aimed to provide a review of imaging features of breast cancer molecular subtypes for the field of precision medicine. We also provide an update on the recent progress in precision medicine for breast cancer, implications for imaging, and recent observations in longitudinal functional imaging with radiomics.

Citations

Citations to this article as recorded by  
  • Circulating non-coding RNAs as a diagnostic and management biomarker for breast cancer: current insights
    Hamed Hosseinalizadeh, Mehrdad Mahmoodpour, Ammar Ebrahimi
    Molecular Biology Reports.2022; 49(1): 705.     CrossRef
  • MRI as a biomarker for breast cancer diagnosis and prognosis
    Francesca Galati, Veronica Rizzo, Rubina Manuela Trimboli, Endi Kripa, Roberto Maroncelli, Federica Pediconi
    BJR|Open.2022;[Epub]     CrossRef
  • Multiparametric MRI Features of Breast Cancer Molecular Subtypes
    Madalina Szep, Roxana Pintican, Bianca Boca, Andra Perja, Magdalena Duma, Diana Feier, Bogdan Fetica, Dan Eniu, Sorin Marian Dudea, Angelica Chiorean
    Medicina.2022; 58(12): 1716.     CrossRef
  • Circulating tumor cells as prognostic biomarkers in breast cancer: current status and future prospects
    Evagelia Chantzara, Nikolaos Xenidis, Galatea Kallergi, Vassilis Georgoulias, Athanasios Kotsakis
    Expert Review of Molecular Diagnostics.2021; 21(10): 1037.     CrossRef
Original Articles
Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma
Tripti Nakra, Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Anant Mohan, Deepali Jain
J Pathol Transl Med. 2021;55(4):279-288.   Published online July 8, 2021
DOI: https://doi.org/10.4132/jptm.2021.05.10
  • 2,486 View
  • 108 Download
  • 3 Citations
AbstractAbstract PDF
Background
Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort.
Methods
This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the
results
were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed.
Conclusions
Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Citations

Citations to this article as recorded by  
  • Expression landscapes in non-small cell lung cancer shaped by the thyroid transcription factor 1
    Herdee Gloriane C. Luna, Marcelo Severino Imasa, Necy Juat, Katherine V. Hernandez, Treah May Sayo, Gloria Cristal-Luna, Sheena Marie Asur-Galang, Mirasol Bellengan, Kent John Duga, Bien Brian Buenaobra, Marvin I. De los Santos, Daniel Medina, Jamirah Sam
    Lung Cancer.2023; 176: 121.     CrossRef
  • Malignant pleural effusion cell blocks are reliable resources for PD-L1 analysis in advanced lung adenocarcinomas: a concordance study with matched histologic samples
    Swati Mahajan, Aruna Nambirajan, Ishan Gupta, Nalini Gupta, Parikshaa Gupta, Deepali Jain
    Journal of the American Society of Cytopathology.2022; 11(5): 253.     CrossRef
  • Clinicopathologic Features and Molecular Biomarkers as Predictors of Epidermal Growth Factor Receptor Gene Mutation in Non-Small Cell Lung Cancer Patients
    Lanlan Liu, Xianzhi Xiong
    Current Oncology.2021; 29(1): 77.     CrossRef
SMARCA4/BRG1 protein-deficient thoracic tumors dictate re-examination of small biopsy reporting in non–small cell lung cancer
Anurag Mehta, Divya Bansal, Rupal Tripathi, Ankush Jajodia
J Pathol Transl Med. 2021;55(5):307-316.   Published online June 21, 2021
DOI: https://doi.org/10.4132/jptm.2021.05.11
  • 4,184 View
  • 215 Download
  • 3 Citations
AbstractAbstract PDF
Background
SMARCA4/BRG1 protein–deficient lung adenocarcinomas and thoracic sarcoma are recently described entities that lack distinctive histological features, transcription termination factor 1 (TTF1) reactivity, and actionable driver mutations. The current diagnostic path for small lung biopsies as recommended by the World Health Organization (WHO, 2015) is likely to categorize these as non– small cell carcinoma–not otherwise specified (NSCC-NOS). The present study attempts to define the subtle but distinctive clinicopathologic features of SMARCA4/BRG1 protein-deficient thoracic tumors; highlight their unique biology; and addresses the unmet need to segregate these using a new, tissue-proficient diagnostic pathway.
Methods
All lung biopsies and those from metastatic sites in patients with suspected advanced lung cancer and classified as NSCC-NOS as per WHO (2015) guidelines were subjected to BRG1 testing by immunohistochemistry. SMARCA4/BRG1 protein–deficient thoracic tumors were evaluated by an extended immunohistochemistry panel. Predictive biomarker and programmed death–ligand 1 testing was conducted in all cases.
Results
Of 110 cases, nine were found to be SMARCA4/BRG1 protein-deficient; six were identified as SMARCA4/BRG1 protein–deficient lung adenocarcinomas, and three were SMARCA4/BRG1 protein-deficient thoracic sarcomas. The histology ranged from poorly differentiated to undifferentiated to rhabdoid. None of the cases showed significant expression of TTF1 or p40, and no actionable mutation was identified.
Conclusions
It is difficult to separate BRG1-deficient lung adenocarcinomas and thoracic sarcomas based on morphology alone. We propose a diagnostic pathway for small biopsies of thoracic tumors to segregate these distinct entities so that they can be studied more efficaciously for new biomarkers and therapeutic options.

Citations

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  • TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma
    Anurag Mehta, Himanshi Diwan, Divya Bansal, Manoj Gupta
    Journal of Pathology and Translational Medicine.2022; 56(1): 53.     CrossRef
  • Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma
    Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
    World Journal of Clinical Cases.2022; 10(29): 10501.     CrossRef
  • Artificial intelligence platform, RADR®, aids in the discovery of DNA damaging agent for the ultra-rare cancer Atypical Teratoid Rhabdoid Tumors
    Joseph McDermott, Drew Sturtevant, Umesh Kathad, Sudhir Varma, Jianli Zhou, Aditya Kulkarni, Neha Biyani, Caleb Schimke, William C. Reinhold, Fathi Elloumi, Peter Carr, Yves Pommier, Kishor Bhatia
    Frontiers in Drug Discovery.2022;[Epub]     CrossRef
Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations
Dalia Elsers, Doaa F. Temerik, Alia M. Attia, A. Hadia, Marwa T. Hussien
J Pathol Transl Med. 2021;55(3):212-224.   Published online May 11, 2021
DOI: https://doi.org/10.4132/jptm.2021.03.15
  • 2,460 View
  • 99 Download
  • 3 Citations
AbstractAbstract PDF
Background
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM).
Methods
The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry.
Results
Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS.
Conclusions
High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.

Citations

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  • Immunohistochemical surrogates for molecular alterations for the classification and grading of gliomas
    Viharkumar Patel, Sanda Alexandrescu
    Seminars in Diagnostic Pathology.2022; 39(1): 78.     CrossRef
  • Meme Kanseri Hastalarında hTERT Gen Ekspresyonunun Klinikopatolojik Önemi
    Ebubekir DİRİCAN, Burak KANKAYA, Zeynep TATAR
    Sağlık Bilimlerinde Değer.2022; : 22.     CrossRef
  • Prognostic and predictive markers in glioblastoma and ALK overexpression
    Jang-Hee Kim
    Journal of Pathology and Translational Medicine.2021; 55(3): 236.     CrossRef
Review
Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation
Kyu Sang Lee, Gheeyoung Choe
J Pathol Transl Med. 2021;55(3):163-170.   Published online April 7, 2021
DOI: https://doi.org/10.4132/jptm.2021.02.22
  • 2,492 View
  • 123 Download
  • 3 Citations
AbstractAbstract PDF
Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

Citations

Citations to this article as recorded by  
  • PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays
    Harriet Evans, Brendan O’Sullivan, Frances Hughes, Kathryn Charles, Lee Robertson, Philippe Taniere, Salvador Diaz-Cano
    Pathology and Oncology Research.2022;[Epub]     CrossRef
  • Insights on recent innovations in bladder cancer immunotherapy
    Mohamed A. Abd El‐Salam, Claire E.P. Smith, Chong‐Xian Pan
    Cancer Cytopathology.2022; 130(9): 667.     CrossRef
  • What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables
    Andrea Palicelli, Martina Bonacini, Stefania Croci, Cristina Magi-Galluzzi, Sofia Cañete-Portillo, Alcides Chaux, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Maria Paola Bonasoni, Alessandra
    Cells.2021; 10(11): 3166.     CrossRef
Original Articles
The prognostic significance of p16 expression pattern in diffuse gliomas
Jin Woo Park, Jeongwan Kang, Ka Young Lim, Hyunhee Kim, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Sung-Hye Park
J Pathol Transl Med. 2021;55(2):102-111.   Published online December 23, 2020
DOI: https://doi.org/10.4132/jptm.2020.10.22
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  • 3 Citations
AbstractAbstract PDF
Background
CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)–mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas.
Methods
p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression.
Results
A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n=326, p<.001), in the IDH-mutant glioma patients (n=103, p=.010), and in the IDH-mutant astrocytoma patients (n=73, p=.032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n=223, p=.121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n=30, p=.457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p=.008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p=.001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p< .001) and in IDH-mutant glioma groups. (p=.046).
Conclusions
This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.

Citations

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  • Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors
    Hyunhee Kim, Ka Young Lim, Jin Woo Park, Jeongwan Kang, Jae Kyung Won, Kwanghoon Lee, Yumi Shim, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi, Tae Min Kim, Hongseok Yun, Sung-Hye Park
    Laboratory Investigation.2022; 102(2): 160.     CrossRef
  • Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification
    Maher Kurdi, Rana H Moshref, Yousef Katib, Eyad Faizo, Ahmed A Najjar, Basem Bahakeem, Ahmed K Bamaga
    World Journal of Clinical Oncology.2022; 13(7): 567.     CrossRef
  • P16INK4A—More Than a Senescence Marker
    Hasan Safwan-Zaiter, Nicole Wagner, Kay-Dietrich Wagner
    Life.2022; 12(9): 1332.     CrossRef
Automated immunohistochemical assessment ability to evaluate estrogen and progesterone receptor status compared with quantitative reverse transcription-polymerase chain reaction in breast carcinoma patients
Taesung Jeon, Aeree Kim, Chungyeul Kim
J Pathol Transl Med. 2021;55(1):33-42.   Published online December 3, 2020
DOI: https://doi.org/10.4132/jptm.2020.09.29
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  • 3 Citations
AbstractAbstract PDF
Background
This study aimed to investigate the capability of an automated immunohistochemical (IHC) evaluation of hormonal receptor status in breast cancer patients compared to a well-validated quantitative reverse transcription–polymerase chain reaction (RT-qPCR) method.
Methods
This study included 93 invasive breast carcinoma cases that had both standard IHC assay and Oncotype Dx assay results. The same paraffin blocks on which Oncotype Dx assay had been performed were selected. Estrogen receptor (ER) and progesterone receptor (PR) receptor status were evaluated through IHC stains using SP1 monoclonal antibody for ER, and 1E2 monoclonal antibody for PR. All ER and PR immunostained slides were scanned, and invasive tumor areas were marked. Using the QuantCenter image analyzer provided by 3DHISTECH, IHC staining of hormone receptors was measured and converted to histochemical scores (H scores). Pearson correlation coefficients were calculated between Oncotype Dx hormone receptor scores and H scores, and between Oncotype Dx scores and Allred scores.
Results
H scores measured by an automated imaging system showed high concordance with RT-qPCR scores. ER concordance was 98.9% (92/93), and PR concordance was 91.4% (85/93). The correlation magnitude between automated H scores and RT-qPCR scores was high and comparable to those of Allred scores (for ER, 0.51 vs. 0.37 [p=.121], for PR, 0.70 vs. 0.72 [p=.39]).
Conclusions
Automated H scores showed a high concordance with quantitative mRNA expression levels measured by RT-qPCR.

Citations

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  • Marker assessments in ER‐ positive breast cancers: old markers, new applications?
    Joshua J X Li, Gary M Tse
    Histopathology.2023; 82(2): 218.     CrossRef
  • The Story of the Magee Equations: The Ultimate in Applied Immunohistochemistry
    Rohit Bhargava, David J. Dabbs
    Applied Immunohistochemistry & Molecular Morphology.2022;[Epub]     CrossRef
  • Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice
    Pengcheng Lou, Yangfan Shen, Aoxiang Zhuge, Longxian Lv, Xueling Zhu, Yin Yuan, Liya Yang, Kaicen Wang, Bo Li, Lanjuan Li, Joanna B. Goldberg
    Microbiology Spectrum.2021;[Epub]     CrossRef
Case Studies
A sinonasal yolk sac tumor in an adult
Jaehoon Shin, Ji Heui Kim, Kyeong Cheon Jung, Kyung-Ja Cho
J Pathol Transl Med. 2022;56(3):152-156.   Published online January 26, 2022
DOI: https://doi.org/10.4132/jptm.2021.12.09
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  • 2 Citations
AbstractAbstract PDF
Yolk sac tumors (YSTs), which are also called endodermal sinus tumors, are malignant tumors of germ cell origin. These tumors usually occur in the gonads, but 20% of cases have been reported at extragonadal sites. The head and neck is a rarely affected region that accounts for just 1% of all malignant tumors of germ cell origin. In addition, YSTs arise mostly in childhood. We present a rare pathologically pure case of primary adult YST in the sinonasal area. A 45-year-old male patient presented with a rapidly growing mass in the nasal cavity, which caused nasal obstruction and bloody post-nasal drip. The histopathologic features indicated pure YST, and immunohistochemical analysis revealed positive reactivity for Sal-like protein 4 and alpha-fetoprotein. Herein, we discuss the clinical, radiologic, and histologic features of this YST and review other cases of sinonasal YST in adults.

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  • Yolk sac tumor of postpubertal-type does not exhibit immunohistochemical loss of SMARCB1/INI1 and SMARCA4/BRG1…but choriocarcinoma?
    Costantino Ricci, Francesca Ambrosi, Tania Franceschini, Francesca Giunchi, Eugenia Franchini, Francesco Massari, Veronica Mollica, Federico Mineo Bianchi, Maurizio Colecchia, Andres Martin Acosta, Michelangelo Fiorentino
    Pathology - Research and Practice.2023; 241: 154269.     CrossRef
  • A Novel Successful Case of Nasal and Sinus Yolk Sac Tumor With SMARCB1 (INI-1) Deficiency: A Case Report
    Tianyu He, Zhiyu Wang, Hongbo Su, Sihan Li, Zheng He
    Cureus.2022;[Epub]     CrossRef
Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice
Evi Abada, Ifeoma C. Anaya, Othuke Abada, Anthony Lebbos, Rafic Beydoun
J Pathol Transl Med. 2022;56(2):97-102.   Published online January 21, 2022
DOI: https://doi.org/10.4132/jptm.2021.10.28
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  • 2 Citations
AbstractAbstract PDF
Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.

Citations

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  • AIEgens assisted label free DNA supersandwich immunoassay for ultrasensitive α-fetoprotein detection
    Xiaowen Ou, Jingman Dai, Yiting Huang, Xiaoqin Xiong, Zhi Zheng, Xiaoding Lou, Fan Xia
    Giant.2022; 11: 100110.     CrossRef
  • Rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features arising in a patient with ulcerative colitis: a case report
    Takako Kihara, Ryuichi Kuwahara, Kurando Kusunoki, Tomohiro Minagawa, Yuki Horio, Motoi Uchino, Hiroki Ikeuchi, Seiichi Hirota
    World Journal of Surgical Oncology.2022;[Epub]     CrossRef

JPTM : Journal of Pathology and Translational Medicine