Journal of Pathology and Translational Medicine

Original Articles

Characteristics of RET gene mutations in Vietnamese medullary thyroid carcinoma patients: a single-center analysis: Van Hung Pham, Quoc Thang Pham, Minh Nguyen, Hoa Nhat Ngo, Thao Thi Thu Luu, Nha Dao Thi Minh, Trâm Đặng, Anh Tu Thai, Hoang Anh Vu, Dat Quoc Ngo; J Pathol Transl Med. 2025;59(2):125-132. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.01.18

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Abstract PDF Supplementary Material: Background
The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer: Ju Yeon Pyo, Yoon Jin Cha, SoonWon Hong; J Pathol Transl Med. 2024;58(6):310-320. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.29

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Background
Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes.
Methods
This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group.
Results
Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin.
Conclusions
RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

Citations

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The ability of anexelekto (AXL) expression and TERT promoter mutation to predict radioiodine-refractory differentiated thyroid carcinoma
Hasrayati Agustina, Tutik Nur Ayni, Yohana Azhar, Erwin Affandi Soeriadi, Bethy Suryawathy Hernowo
Diagnostic Pathology.2025;[Epub] CrossRef

Case Study

Colorectal cancer with a germline BRCA1 variant inherited paternally: a case report: Kyoung Min Kim, Min Ro Lee, Ae Ri Ahn, Myoung Ja Chung; J Pathol Transl Med. 2024;58(6):341-345. Published online September 5, 2024; DOI: https://doi.org/10.4132/jptm.2024.08.14

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Abstract PDF: BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient’s father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

Review

Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy: Chan Kwon Jung; J Pathol Transl Med. 2023;57(4):208-216. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.20

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Abstract PDF

As the application of core needle biopsy (CNB) in evaluating thyroid nodules rises in clinical practice, the 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules have officially recognized its value for the first time. CNB procures tissue samples preserving both histologic structure and cytologic detail, thereby supplying substantial material for an accurate diagnosis and reducing the necessity for repeated biopsies or subsequent surgical interventions. The current review introduces the risk of malignancy within distinct diagnostic categories, emphasizing the implications of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on these malignancy risks. Prior research has indicated diagnostic challenges associated with follicular-patterned lesions, resulting in notable variation within indeterminate diagnostic categories. The utilization of mutation-specific immunostaining in CNB enhances the accuracy of lesion classification. This review underlines the essential role of a multidisciplinary approach in diagnosing follicular-patterned lesions and the potential of mutation-specific immunostaining to strengthen diagnostic consensus and inform patient management decisions.

Citations

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Diagnostic implication of thyroid spherules for cytological diagnosis of thyroid nodules
Heeseung Sohn, Kennichi Kakudo, Chan Kwon Jung
Cytopathology.2024; 35(3): 383. CrossRef
A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules
Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na
Endocrinology and Metabolism.2024; 39(1): 61. CrossRef
The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy
Hye Hyeon Moon, Sae Rom Chung, Young Jun Choi, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Jeong Hyun Lee, Jung Hwan Baek
Endocrinology and Metabolism.2024; 39(2): 300. CrossRef
Core needle biopsy for thyroid nodules assessment-a new horizon?
David D Dolidze, Serghei Covantsev, Grigorii M Chechenin, Natalia V Pichugina, Anastasia V Bedina, Anna Bumbu
World Journal of Clinical Oncology.2024; 15(5): 580. CrossRef
Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning
Agnes Stephanie Harahap, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2024; 58(5): 205. CrossRef
A simplified four-tier classification for thyroid core needle biopsy
M. Paja, J. L. Del Cura, R. Zabala, I. Korta, Mª T. Gutiérrez, A. Expósito, A. Ugalde
Journal of Endocrinological Investigation.2024; 48(4): 895. CrossRef

Original Articles

Founder BRCA1 mutations in Nepalese population: Anurag Mehta, Himanshi Diwan, Garima Gupta, Shrinidhi Nathany, Shalini Agnihotri, Surender Dhanda; J Pathol Transl Med. 2022;56(4):212-216. Published online June 15, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.02

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Abstract PDF

Background
Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people.
Methods
Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021. One thousand one hundred thirtythree probands were screened for germline BRCA variants by next generation sequencing. The variants were classified as per the American Society of Medical Genetics and Genomics recommendations. Pathogenic (class V) and likely pathogenic (class IV) were considered clinically relevant and utilized for cascade screening.
Results
Nepalese population made up a subcohort of 5.12% (58/1,133) of probands tested for germline BRCA1/2 variants. Twenty-seven of these 58 tested harbored pathogenic genetic alterations in BRCA1/2 genes, with 23 being BRCA1 mutant. Sixteen of 23 BRCA1 mutant cases shared one common pathogenic mutation c.2214_2215insT (p.Lys739Ter) (NM_007294.4). Additionally, a second highly recurrent mutation in BRCA1 gene c.5068A>T (p.Lys1690Ter) (NM_007294.4) was noted in six patients from this population.
Conclusions
The overwhelming abundance of the above two variants in a geographically confined population confers these two genetic alterations a status of founder mutations amongst the people of Nepal. A more extensive population-based study to reaffirm these findings will help establish a dual site-specific germline testing similar to the “Multisite-3-assay” in Ashkenazi Jews as the primary screening tool, especially in a resource-constrained environment.

Citations

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Hiding in plain sight: a partial deletion ofBRCA1exon 7 undetectable by MLPA is a Nepali founder variant
Virginia Clowes, Jenny C Taylor, Alistair T Pagnamenta
Journal of Medical Genetics.2025; 62(2): 54. CrossRef
Finding significance: New perspectives in variant classification of the RAD51 regulators, BRCA2 and beyond
Hayley L. Rein, Kara A. Bernstein
DNA Repair.2023; 130: 103563. CrossRef
Digital PCR as a Highly Sensitive Diagnostic Tool: A Review
K. V. Kopylova, Ed. W. Kasparov, I. V. Marchenko, M. V. Smolnikova
Molecular Biology.2023; 57(5): 793. CrossRef
Digital PCR as a Highly Sensitive Diagnostic Tool: a Review
K. V. Kopylova, Ed. W. Kasparov, I. V. Marchenko, M. V. Smolnikova
Молекулярная биология.2023; 57(5): 771. CrossRef

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand: Arunee Dechaphunkul, Phatcharaporn Thongwatchara, Paramee Thongsuksai, Tanadech Dechaphunkul, Sarayut Lucien Geater; J Pathol Transl Med. 2022;56(3):126-133. Published online February 28, 2022; DOI: https://doi.org/10.4132/jptm.2022.01.04

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Abstract PDF

Background
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC.
Methods
Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations.
Results
The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations.
Conclusions
The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Citations

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An empirical review on the resistance mechanisms of epidermal growth factor receptor inhibitors and predictive molecular biomarkers in colorectal cancer
Sankha Bhattacharya
Critical Reviews in Oncology/Hematology.2023; 183: 103916. CrossRef

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

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Abstract 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

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Baseline retinoblastoma transcriptional corepressor 1 (Rb1) functional inactivation is a pre-requisite but not sufficient for small-cell histological transformation in epidermal growth factor receptor (EGFR) mutant lung adenocarcinomas post-tyrosine kinas
Aruna Nambirajan, Amber Rathor, Hemavathi Baskarane, Anju GS, Sachin Khurana, Somagattu Sushmitha, Aparna Sharma, Prabhat Singh Malik, Deepali Jain
Virchows Archiv.2025;[Epub] CrossRef
Mutation profile and programmed death ligand 1 status of patients with non‐small cell lung cancer diagnosed with “adenocarcinoma” and “non‐small cell carcinoma favor adenocarcinoma”
Naoko Shigeta, Tomoyuki Yokose, Shuji Murakami, Tetsuya Isaka, Kanako Shinada, Emi Yoshioka, Atsuya Narita, Kengo Katakura, Tetsuro Kondo, Terufumi Kato, Takuya Nagashima, Haruhiro Saito, Hiroyuki Ito
Thoracic Cancer.2024; 15(6): 458. CrossRef
Significance of NKX2-1 as a biomarker for clinical prognosis, immune infiltration, and drug therapy in lung squamous cell carcinoma
Huiyue Lin, Juyong Wang, Qing Shi, Minmin Wu
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TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities
Katharina Möller, Tayyaba Gulzar, Maximilian Lennartz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Ahmed Abdulwahab Bawahab, Ronald Simon, Till S. Clauditz, Guido Sauter, Ria Schlichter, Andrea Hinsch, Simon Kind, Frank Jac
Virchows Archiv.2024; 485(5): 815. CrossRef
Identifying immunohistochemical biomarkers panel for non-small cell lung cancer in optimizing treatment and forecasting efficacy
Xiaoya Zhang, Junhong Meng, Mingyue Gao, Cheng Gong, Cong Peng, Duxian Liu
BMC Cancer.2024;[Epub] CrossRef
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

A study of pathological characteristics and BRAF V600E status in Langerhans cell histiocytosis of Vietnamese children: Thu Dang Anh Phan, Bao Gia Phung, Tu Thanh Duong, Vu Anh Hoang, Dat Quoc Ngo, Nguyen Dinh The Trinh, Tung Thanh Tran; J Pathol Transl Med. 2021;55(2):112-117. Published online January 27, 2021; DOI: https://doi.org/10.4132/jptm.2020.11.30

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Abstract PDF

Background
Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH.
Methods
We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed.
Results
BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF V600E mutation rate than a single system (p=.001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression.
Conclusions
In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.

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Pathologic characteristics of histiocytic and dendritic cell neoplasms
Sun Och Yoon
Blood Research.2024;[Epub] CrossRef
Sulfur dots/Au@Ag nanorods array-based polarized ECL sensor for the detection of thyroid cancer biomarker
Zixuan Ding, Peilin Wang, Zhenrun Li, Yupeng Guo, Qiang Ma
Talanta.2023; 265: 124925. CrossRef

Highly prevalent BRAF V600E and low-frequency TERT promoter mutations underlie papillary thyroid carcinoma in Koreans: Sue Youn Kim, Taeeun Kim, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Chan Kwon Jung; J Pathol Transl Med. 2020;54(4):310-317. Published online June 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.05.12

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Abstract PDF

Background
The presence of telomerase reverse transcriptase (TERT) promoter mutations have been associated with a poor prognosis in patients with papillary thyroid carcinomas (PTC). The frequency of TERT promoter mutations varies widely depending on the population and the nature of the study.
Methods
Data were prospectively collected in 724 consecutive patients who underwent thyroidectomy for PTC from 2018 to 2019. Molecular testing for BRAF V600E and TERT promoter mutations was performed in all cases.
Results
TERT promoter alterations in two hotspots (C228T and C250T) and C216T were found in 16 (2.2%) and 4 (0.6%) of all PTCs, respectively. The hotspot mutations were significantly associated with older age at diagnosis, larger tumor size, extrathyroidal extension, higher pathologic T category, lateral lymph node metastasis, and higher American Thyroid Association recurrence risk. The patients with C216T variant were younger and had a lower American Thyroid Association recurrence risk than those with hotspot mutations. Concurrent BRAF V600E was found in 19 of 20 cases with TERT promoter mutations. Of 518 microcarcinomas measuring ≤1.0 cm in size, hotspot mutations and C216T variants were detected in five (1.0%) and three (0.6%) cases, respectively.
Conclusions
Our study indicates a low frequency of TERT promoter mutations in Korean patients with PTC and supports previous findings that TERT promoter mutations are more common in older patients with unfavorable clinicopathologic features and BRAF V600E. TERT promoter mutations in patients with microcarcinoma are uncommon and may have a limited role in risk stratification. The C216T variant seems to have no clinicopathologic effect on PTC.

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Review

Tumor immune response and immunotherapy in gastric cancer: Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee; J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.08

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Abstract PDF

Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.

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Original Articles

Molecular and Clinicopathological Features of Gastrointestinal Stromal Tumors in Vietnamese Patients: Quoc Dat Ngo, Quoc Thang Pham, Dang Anh Thu Phan, Anh Vu Hoang, Thi Ngoc Ha Hua, Sao Trung Nguyen; J Pathol Transl Med. 2019;53(6):361-368. Published online September 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.08.27

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Abstract PDF Supplementary Material

Background
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.
Methods
We first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.
Results
The largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.
Conclusions
The expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.

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Ki67 for evaluating the prognosis of gastrointestinal stromal tumors: A systematic review and meta‑analysis
Ji Li, An-Ran Wang, Xiao-Dong Chen, Hong Pan, Shi-Qiang Li
Oncology Letters.2022;[Epub] CrossRef
Endoscopic ultrasound‐guided fine‐needle aspiration cytology in the diagnosis of the gastrointestinal stromal tumor of the stomach
José‐Fernando Val‐Bernal, Elena Yllera, María Moris, Ihab Abdulkader Nallib, Angel Vázquez‐Boquete, María Martino
Diagnostic Cytopathology.2020; 48(9): 833. CrossRef

Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung Cancer: Ji Yeon Kim, Woo Jeong Lee, Ha Young Park, Ahrong Kim, Dong Hoon Shin, Chang Hun Lee; J Pathol Transl Med. 2018;52(5):275-282. Published online August 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.29

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Abstract PDF Supplementary Material

Background
MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post-transcriptional gene regulation. They are commonly deregulated in human malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
Methods
Six cases of resected NSCLC harboring the T790M mutation were examined. We performed miRNA time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially expressed between the two groups were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Results
miRNA PCR array profiling revealed three up-regulated miRNAs whose expression levels were altered 4.0-fold or more in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change, 4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The three differentially expressed miRNAs were validated by qRT-PCR, and they were found to be overexpressed in the T790M group relative to L858R group. In particular, expression levels of miR-1 and miR-124 were significantly higher in the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096).
Conclusions
MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated NSCLC.

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Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages
Hao Ho, Sung-Liang Yu, Hsuan-Yu Chen, Shin-Sheng Yuan, Kang-Yi Su, Yi-Chiung Hsu, Chung-Ping Hsu, Cheng-Yen Chuang, Ya-Hsuan Chang, Yu-Cheng Li, Chiou-Ling Cheng, Gee-Chen Chang, Pan-Chyr Yang, Ker-Chau Li
Lung Cancer.2023; 184: 107352. CrossRef
Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
Alessandro Leonetti, Mjriam Capula, Roberta Minari, Giulia Mazzaschi, Alessandro Gregori, Btissame El Hassouni, Filippo Papini, Paola Bordi, Michela Verzè, Amir Avan, Marcello Tiseo, Elisa Giovannetti
Cells.2021; 10(6): 1520. CrossRef
Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
Nalini Devi Verusingam, Yi-Chen Chen, Heng-Fu Lin, Chao-Yu Liu, Ming-Cheng Lee, Kai-Hsi Lu, Soon-Keng Cheong, Alan Han-Kiat Ong, Shih-Hwa Chiou, Mong-Lien Wang
Journal of the Chinese Medical Association.2021; 84(3): 248. CrossRef
Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands
Sarah Sayed Hassanein, Sherif Abdelaziz Ibrahim, Ahmed Lotfy Abdel-Mawgood
International Journal of Molecular Sciences.2021; 22(22): 12496. CrossRef
The Roles of MicroRNA in Lung Cancer
Kuan-Li Wu, Ying-Ming Tsai, Chi-Tun Lien, Po-Lin Kuo, Jen-Yu Hung
International Journal of Molecular Sciences.2019; 20(7): 1611. CrossRef

Utility of BRAF VE1 Immunohistochemistry as a Screening Tool for Colorectal Cancer Harboring BRAF V600E Mutation: Jeong-Hwa Kwon, Byung-Kwan Jeong, Yong Sik Yoon, Chang Sik Yu, Jihun Kim; J Pathol Transl Med. 2018;52(3):157-163. Published online March 29, 2018; DOI: https://doi.org/10.4132/jptm.2018.03.28

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Abstract PDF Supplementary Material

Background
BRAF mutation has been recognized as an important biomarker of colorectal cancer (CRC) for targeted therapy and prognosis prediction. However, sequencing for every CRC case is not cost-effective. An antibody specific for BRAF V600E mutant protein has been introduced, and we thus examined the utility of BRAF VE1 immunohistochemistry for evaluating BRAF mutations in CRC.
Methods
Fifty-one BRAF-mutated CRCs and 100 age and sexmatched BRAF wild-type CRCs between 2005 and 2015 were selected from the archives of Asan Medical Center. Tissue microarrays were constructed and stained with BRAF VE1 antibody.
Results
Forty-nine of the 51 BRAF-mutant CRCs (96.1%) showed more than moderate cytoplasmic staining, except for two weakly stained cases. Six of 100 BRAF wild-type cases also stained positive with BRAF VE1 antibody; four stained weakly and two stained moderately. Normal colonic crypts showed nonspecific weak staining, and a few CRC cases exhibited moderate nuclear reactivity (3 BRAF-mutant and 10 BRAF wild-type cases). BRAF-mutated CRC patients had higher pathologic stages and worse survival than BRAF wild-type patients.
Conclusions
BRAF VE1 immunohistochemistry showed high sensitivity and specificity, but occasional nonspecific staining in tumor cell nuclei and normal colonic crypts may limit their routine clinical use. Thus, BRAF VE1 immunohistochemistry may be a useful screening tool for BRAF V600E mutation in CRCs, provided that additional sequencing studies can be done to confirm the mutation in BRAF VE1 antibody-positive cases.

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The Significance of TROP2 Expression in Predicting BRAF Mutations in Papillary Thyroid Carcinoma: Joon Seog Kong, Hyeon Jin Kim, Min-Jung Kim, Areumnuri Kim, Dalnim Lee, Kanghee Han, Sunhoo Park, Jae Soo Koh, Jae Kyung Myung; J Pathol Transl Med. 2018;52(1):14-20. Published online December 11, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.17

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Abstract PDF

Background
Trophoblast antigen 2 (TROP2) is a human trophoblast cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC.
Methods
First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal thyroid cell line. Additionally, we checked TROP2 protein levels in a normal thyroid cell line after introduction of the BRAF V600E mutation.
Results
In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p<.001). Upregulation of TROP2 mRNA was observed in all three thyroid cancer cell lines, but not in the normal thyroid cell line. Interestingly, however, the TROP2 expression was increased in the normal thyroid cell line after introduction of the BRAF V600E mutation.
Conclusions
Based on these results, we concluded that TROP2 expression is significantly associated with BRAF mutation and that TROP2 immunohistochemistry could be used for predicting BRAF mutations or diagnosing papillary thyroid carcinoma.

Citations

Citations to this article as recorded by

Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma
Amany Selim Attia, Samia Hussein, Hend Sameh, Amr Khalil, Ahmad Barakat Waley, Ihab Matar, Reham Sameh
Cancer Biomarkers.2024; 39(3): 211. CrossRef
BRAF mutation, selected miRNAs and genes expression in primary papillary thyroid carcinomas and local lymph node metastases
David Kalfert, Marie Ludvikova, Martin Pesta, Tommi Hakala, Lucie Dostalova, Hana Grundmannova, Jindra Windrichova, Katerina Houfkova, Tereza Knizkova, Jaroslav Ludvik, Jiri Polivka, Ivana Kholova
Pathology - Research and Practice.2024; 258: 155319. CrossRef
Unveiling the placental secrets: Exploring histopathological changes and TROP2 expression in intrahepatic cholestasis of pregnancy
Cezmi Baran Ozalp, Sozdar Akdogan, Dilan Cetinavci, Melike Nur Akin, Hulya Elbe, Burcu Kasap
Placenta.2024; 154: 201. CrossRef
Trop2-Targeted Molecular Imaging in Solid Tumors: Current Advances and Future Outlook
Yongshun Liu, Wenpeng Huang, Rachel J. Saladin, Jessica C. Hsu, Weibo Cai, Lei Kang
Molecular Pharmaceutics.2024; 21(12): 5909. CrossRef
TROP2 is a Good Indicator for Infiltrative Nature of Carcinoma Rather than Diagnosing Malignancy in Thyroid
E. Kılınc, P. Gunes, A. Doganer
Indian Journal of Otolaryngology and Head & Neck Surgery.2022; 74(S2): 2560. CrossRef
Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer
Xinlin Liu, Junwen Deng, Yang Yuan, Wujun Chen, Wenshe Sun, Yanhong Wang, Haiming Huang, Bing Liang, Tao Ming, Jialian Wen, Binghuan Huang, Dongming Xing
Pharmacology & Therapeutics.2022; 239: 108296. CrossRef
Knockdown of Trop2 inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/β‐catenin pathway
Xiaotong Sun, Guangyang Xing, Cui Zhang, Kun Lu, Yuqiong Wang, Xiyan He
Cell Biochemistry and Function.2020; 38(2): 141. CrossRef
Can TROP2 be used as a prognostic marker in endometrioid endometrial carcinoma?
SerkanY Celik, Özgürİlhan Çelik
Indian Journal of Pathology and Microbiology.2020; 63(3): 418. CrossRef
Diagnostic Value of TROP-2 and CK19 Expression in Papillary Thyroid Carcinoma in Both Surgical and Cytological Specimens
Asmaa Gaber Abdou, Mohammed Shabaan, Rania Abdallha, Nehal Nabil
Clinical Pathology.2019;[Epub] CrossRef
Evaluation of Diagnostic Utility of Immunohistochemistry Markers of TROP-2 and HBME-1 in the Diagnosis of Thyroid Carcinoma
Nooshin Zargari, Maral Mokhtari
European Thyroid Journal.2019; 8(1): 1. CrossRef
The diagnostic value of TROP-2, SLP-2 and CD56 expression in papillary thyroid carcinoma
Xueyang Yang, Yifang Hu, He Shi, Chengzhou Zhang, Zhixiao Wang, Xiaoyun Liu, Huanhuan Chen, Lijuan Zhang, Dai Cui
European Archives of Oto-Rhino-Laryngology.2018; 275(8): 2127. CrossRef
TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling
Qing‑Zhi Gu, Abulimiti Nijiati, Xing Gao, Kai‑Liang Tao, Cheng‑Duo Li, Xue‑Peng Fan, Zheng Tian
Molecular Medicine Reports.2018;[Epub] CrossRef

Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors: Hui Jeong Jeong, Chang Gok Woo, Bora Lee, Shin Kwang Khang, Soo Jeong Nam, Jene Choi; J Pathol Transl Med. 2018;52(2):71-78. Published online October 18, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.21

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201 Download
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Abstract PDF Supplementary Material

Background
Protein phosphatase magnesium-dependent 1δ (PPM1D) is a p53-induced serine/ threonine phosphatase, which is overexpressed in various human cancers. A recent study reported that a mutation in the PPM1D gene is associated with poor prognosis in brainstem gliomas. In this study, we evaluated the utility of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and oligodendroglial tumors.
Methods
To investigate PPM1D protein expression, mRNA expression, and copy number changes, immunohistochemistry, RNAscope in situ hybridization, and fluorescence in situ hybridization were performed in 84 adult supratentorial diffuse gliomas. We further analyzed clinical characteristics and overall survival (OS) according to PPM1D protein expression, and examined its correlation with other glioma biomarkers such as isocitrate dehydrogenase (IDH) mutation, and p53 expression.
Results
Forty-six cases (54.8%) were PPM1D-positive. PPM1D expression levels were significantly correlated with PPM1D transcript levels (p= .035), but marginally with PPM1D gene amplification (p=.079). Patients with high-grade gliomas showed a higher frequency of PPM1D expression than those with low-grade gliomas (p <.001). Multivariate analysis demonstrated that PPM1D expression (hazard ratio [HR], 2.58; p=.032), age over 60 years (HR, 2.55; p=.018), and IDH1 mutation (HR, 0.18; p=.002) were significantly independent prognostic factors; p53 expression had no prognostic significance (p=.986). The patients with tumor expressing PPM1D showed a shorter OS (p=.003). Moreover, patients with tumor harboring wild-type IDH1 and PPM1D expression had the worst OS (p<.001).
Conclusions
Our data suggest that a subset of gliomas express PPM1D; PPM1D expression is a significant marker of poor prognosis in adult supratentorial diffuse astrocytic and oligodendroglial tumors.

Citations

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Yaning Wang, Junlin Li, Yaning Cao, Wenlin Chen, Hao Xing, Xiaopeng Guo, Yixin Shi, Yuekun Wang, Tingyu Liang, Liguo Ye, Delin Liu, Tianrui Yang, Yu Wang, Wenbin Ma
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