Journal of Pathology and Translational Medicine

Case Study

Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review: Priyanka Singh, Aruna Nambirajan, Manish Kumar Gaur, Rahul Raj, Sunil Kumar, Prabhat Singh Malik, Deepali Jain; J Pathol Transl Med. 2022;56(4):231-237. Published online July 7, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.08

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Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

Citations

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Mediastinal epithelioid inflammatory myofibroblastic sarcoma with the EML4‐ALK fusion: A case report and literature review
Tingyu Pan, Xinyu Sun, Xiao Wu, Futing Tang, Xianmei Zhou, Qian Wang, Shi Chen
Respirology Case Reports.2024;[Epub] CrossRef
Case report: Epithelioid inflammatory myofibroblastic sarcoma treated with an ALK TKI ensartinib
Mengmeng Li, Ruyue Xing, Jiuyan Huang, Chao Shi, Chunhua Wei, Huijuan Wang
Frontiers in Oncology.2023;[Epub] CrossRef
Epithelioid Inflammatory Myofibroblastic Sarcoma With Poor Response to Crizotinib: A Case Report
Soheila Aminimoghaddam, Roghayeh Pourali
Clinical Medicine Insights: Case Reports.2023;[Epub] CrossRef
Epithelioid inflammatory myofibroblastic sarcoma: a case report and brief literature review
Weidong Dou, Yu Guan, Tao Liu, Hang Zheng, Shuo Feng, Yingchao Wu, Xin Wang, Zhanbing Liu
Frontiers in Oncology.2023;[Epub] CrossRef

Original Article

Multistaining Optimization for Epstein-Barr Virus–Encoded RNA In Situ Hybridization and Immunohistochemistry of Formalin-Fixed Paraffin-Embedded Tissues Using an Automated Immunostainer: Jae Nam Ko, Jin Kyoung Jung, Yun Ik Park, Hwa Jeong Shin, Jooryung Huh, Sol Back, Yu Jin Kim, Jae Ho Kim, Heounjeong Go; J Pathol Transl Med. 2019;53(5):317-326. Published online August 27, 2019; DOI: https://doi.org/10.4132/jptm.2019.08.06

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Abstract PDF Supplementary Material

Background
Single staining is commonly performed for practical pathologic diagnoses. However, this method is limited in its ability to specify cellular morphology and immunophenotype and often requires consumption of limited tissue. This study aimed to describe an optimized protocol for multiple in situ hybridization (ISH) and immunohistochemistry (IHC).
Methods
The quality of multistaining was evaluated by carefully changing each step of ISH and IHC in an angioimmunoblastic T-cell lymphoma (AITL) case on a Ventana BenchMark XT automated immunostainer. The optimized protocols were also performed using another immunostainer and in 15 cases of five Epstein-Barr virus (EBV)–associated malignancies using formalin-fixed paraffin-embedded tissue.
Results
The quality of various ISHIHC staining protocols was semi-quantitatively evaluated. The best EBV-encoded RNA (EBER)-ISH/double IHC staining quality, equivalent to single staining, was obtained using the following considerations: initial EBER-ISH application, use of protease and antigen retrieval reagent (cell conditioning 1 [CC1] treatment time was minimized due to impact on tissue quality), additional baking/ deparaffinization not needed, and reduced dilution ratio and increased reaction time for primary antibody compared with single immunostaining. Furthermore, shorter second CC1 treatment time yielded better results. Multiple staining was the best quality in another immunostainer and for different types of EBV-associated malignancies when it was performed in the same manner as for the Ventana BenchMark XT as determined for AITL.
Conclusions
EBER-ISH and double IHC could be easily used in clinical practice with currently available automated immunostainers and adjustment of reagent treatment time, dilution ratio, and antibody reaction time.

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Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Shilah A. Bonnett, Alyssa B. Rosenbloom, Giang T. Ong, Mark Conner, Aric B.E. Rininger, Daniel Newhouse, Felicia New, Chi Q. Phan, Saskia Ilcisin, Hiromi Sato, John S. Lyssand, Gary Geiss, Joseph M. Beechem
Cancer Research Communications.2023; 3(5): 763. CrossRef
Detection of Epstein–Barr Virus in Periodontitis: A Review of Methodological Approaches
Lilit Tonoyan, Marlène Chevalier, Séverine Vincent-Bugnas, Robert Marsault, Alain Doglio
Microorganisms.2020; 9(1): 72. CrossRef

Review

Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives: Yoon Kyung Jeon, Sun Och Yoon, Jin Ho Paik, Young A Kim, Bong Kyung Shin, Hyun-Jung Kim, Hee Jeong Cha, Ji Eun Kim, Jooryung Huh, Young-Hyeh Ko; J Pathol Transl Med. 2017;51(3):224-241. Published online May 10, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.09

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Abstract PDF

Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

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Assessment of Bone Marrow Involvement in B‐Cell non‐Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next‐Generation Sequencing
Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul Won Choi, Ha Nui Kim, Jung Ah Kwon, Soo‐Young Yoon, Jung Yoon
Journal of Clinical Laboratory Analysis.2024;[Epub] CrossRef
Thymus and lung mucosa-associated lymphoid tissue lymphoma with adenocarcinoma of the lung: a case report and literature review
Yu Pang, Daosheng Li, Yiqian Chen, Qinqin Liu, Yuheng Wu, Qingliang Teng, Yuyu Liu
World Journal of Surgical Oncology.2023;[Epub] CrossRef
Development and implementation of an automated and highly accurate reporting process for NGS-based clonality testing
Sean T. Glenn, Phillip M. Galbo, Jesse D. Luce, Kiersten Marie Miles, Prashant K. Singh, Manuel J. Glynias, Carl Morrison
Oncotarget.2023; 14(1): 450. CrossRef
A comparison of capillary electrophoresis and next-generation sequencing in the detection of immunoglobulin heavy chain H and light chain κ gene rearrangements in the diagnosis of classic hodgkin’s lymphoma
Juan-Juan Zhang, Yu-Xin Xie, Li-Lin Luo, Xuan-Tao Yang, Yi-Xing Wang, Yue Cao, Zheng-Bo Long, Wan-Pu Wang
Bioengineered.2022; 13(3): 5868. CrossRef
Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies
Jiwon Koh, Sun Ah Shin, Ji Ae Lee, Yoon Kyung Jeon
Journal of Pathology and Translational Medicine.2022; 56(4): 173. CrossRef
Diagnostic Workup of Primary Cutaneous B Cell Lymphomas: A Clinician's Approach
Giulia Tadiotto Cicogna, Martina Ferranti, Mauro Alaibac
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Kappa and lambda immunohistochemistry and in situ hybridization in the evaluation of atypical cutaneous lymphoid infiltrates
Alexandra C. Hristov, Nneka I. Comfere, Claudia I. Vidal, Uma Sundram
Journal of Cutaneous Pathology.2020; 47(11): 1103. CrossRef
Primary lung mucosa-associated lymphoid tissue lymphoma accompanied by multiple sclerosis
Ke-Ke Yu, Lei Zhu, Ji-Kai Zhao, Rui-Ying Zhao, Yu-Chen Han
Chinese Medical Journal.2019; 132(13): 1625. CrossRef
Diagnostic accuracy of SOX11 immunohistochemistry in mantle cell lymphoma: A meta-analysis
Woojoo Lee, Eun Shin, Bo-Hyung Kim, Hyunchul Kim, Riccardo Dolcetti
PLOS ONE.2019; 14(11): e0225096. CrossRef
Views of dermatopathologists about clonality assays in the diagnosis of cutaneous T‐cell and B‐cell lymphoproliferative disorders
Nneka Comfere, Uma Sundram, Maria Yadira Hurley, Brian Swick
Journal of Cutaneous Pathology.2018; 45(1): 39. CrossRef
A Next-Generation Sequencing Primer—How Does It Work and What Can It Do?
Yuriy O. Alekseyev, Roghayeh Fazeli, Shi Yang, Raveen Basran, Thomas Maher, Nancy S. Miller, Daniel Remick
Academic Pathology.2018; 5: 2374289518766521. CrossRef

Case Reports

Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of Relevant Literature on Korean Women: Sung Jong Lee, Hyun Joo Choi; Korean J Pathol. 2012;46(4):395-398. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.395

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Abstract PDF

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare tumor with unclear pathogenesis. A 54-year-old postmenopausal woman presented with a 6-month history of vaginal bleeding. The patient was provisionally diagnosed with uterine submucosal leiomyoma. This was followed by total hysterectomy with a bilateral salpingo-oophorectomy under the laparoscopic guidance. Histopathologically, the tumor was PESCC which was accompanied by a lack of the tumor in the uterine cervix. The tumor showed positive immunoreactivity for p^16INK4a. But there was no evidence of human papillomavirus (HPV) on in situ hybridization and HPV DNA chip analysis. We also present a review of the relevant literature on Korean women.

Citations

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p16 Block Type Overexpression, p53 Wild Type Reactivity, and Cervical Involvement do not Always Exclude the Diagnosis of Primary Endometrial Squamous Cell Carcinoma (PESCC)
Daniela Fanni, Clara Gerosa, Michele Peiretti, Valerio Mais, Elena Massa, Stefano Angioni, Gavino Faa
International Journal of Gynecological Pathology.2024; 43(2): 200. CrossRef
Pathogenetic characteristics of endometrioid adenocarcinoma of uterus at present stage
T. I. Moiseenko, S. V. Shatalova, E. M. Nepomnyashchaya, V. A. Bandovkina, M. L. Adamyan
Medical alphabet.2024; (36): 35. CrossRef
Treatment of primary squamous cell carcinoma of the endometrium and review of previous literature: A case report
Liyun Song, Qi Wu, Suning Bai, Ren Xu, Xiaona Wang, Yanyan Yang
Medicine.2023; 102(17): e33667. CrossRef
Prevalence of human papilloma virus and Chlamydia trachomatis in endometrial and cervical carcinoma: a comparative study in North Indian women
Heena Gautam, Sumita Mehta, Nidhi Nayar, Neha Kumar, Syed Akhtar Husain, Mausumi Bharadwaj
Systems Biology in Reproductive Medicine.2023; 69(6): 399. CrossRef
PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature
Daniela Fanni, Michele Peiretti, Valerio Mais, Elena Massa, Clara Gerosa, Francesca Ledda, Maria Luisa Fais, Gavino Faa, Stefano Angioni
International Journal of Gynecological Pathology.2022; 41(4): 431. CrossRef
Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations
Mark R. Hopkins, Doreen N. Palsgrove, Brigitte M. Ronnett, Russell Vang, Jeffrey Lin, Tricia A. Murdock
American Journal of Surgical Pathology.2022; 46(12): 1611. CrossRef
Primary squamous cell carcinoma of the endometrium—Case report with cytological characteristics in direct and indirect endometrial samples
Sanda Rajhvajn, Ana Barišić, Lada Škopljanac‐Mačina, Danijela Jurič, Vesna Mahovlić
Cytopathology.2021; 32(6): 823. CrossRef
Primary squamous cell carcinoma of the endometrium associated with human papilloma virus in a young woman: a case report
Tchin Darré, Abdoul-Samadou Aboubakari, Lantam Sonhaye, Baguilane Douaguibe, Akila Bassowa, Gado Napo-Koura
Journal of Medical Case Reports.2019;[Epub] CrossRef
Primary squamous cell carcinoma of the endometrium in a woman of perimenopausal age
Chao Zhang, Hongyan Zhang, Linqing Yang, Yunfei Wang, Xiaoyu Li, Jinfeng Guo, Jing Xu
Medicine.2018; 97(48): e13418. CrossRef
S100P is Overexpressed in Squamous Cell and Adenosquamous Carcinoma Subtypes of Endometrial Cancer and Promotes Cancer Cell Proliferation and Invasion
Hongfei Jiang, Hang Hu, Fan Lin, Yoon Pin Lim, Yunfen Hua, Xiaomei Tong, Songying Zhang
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Überraschung in der Abradatdiagnostik
U. Kellner, A. Kellner, U. Cirkel
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Primary Pulmonary Myxoid Liposarcoma with Translocation t(12;16)(q13;p11) in a Young Female Patient: A Brief Case Report: Choonhee Son, Phil Jo Choi, Mee Sook Roh; Korean J Pathol. 2012;46(4):392-394. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.392

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Abstract PDF

Primary liposarcoma of the lung is an extremely rare disease. To date, only 14 cases have been reported in the literature. We experienced a case of myxoid liposarcoma of the lung treated by surgery. The tumor was well-defined, solid, lobulated mass measuring 3.5×2 cm, involving the bronchus of the left lower lobe. Microscopically, myxoid liposarcoma was identified. The fluorescence in situ hybridization confirmed the presence of a reciprocal translocation involving DNA damage-inducible transcript 3 (DDIT3) and fused in sarcoma (FUS) genes. The patient is still alive with no recurrence or metastasis at the time of writing this report (on 20 months postoperatively). To our knowledge, this is the first cytogenetic case report of pulmonary myxoid liposarcoma.

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Primary intrathoracic liposarcomas: A clinicopathologic and molecular study of 43 cases in one of the largest medical centers of China
You Xie, Wenyi Jing, Wei Zhao, Ran Peng, Min Chen, Ting Lan, Heng Peng, Xin He, Huijiao Chen, Zhang Zhang, Hongying Zhang
Frontiers in Oncology.2022;[Epub] CrossRef
Primary Pulmonary Liposarcoma with Pancreatic Metastasis: A Rarest of Rare Intrathoracic Malignancy
Anirban Halder, Rituparna Biswas, Sujit Shukla, Nisha Rana, Vikas Yadav, Jaspreet Kaur
Indian Journal of Medical and Paediatric Oncology.2020; 41(04): 605. CrossRef
Primary dedifferentiated liposarcoma of the lung with rhabdomyoblastic and chrondroblastic differentiation
Anthony Longano, Alexandra DuGuesclin, Catherine Mitchell
Histopathology.2015; 67(6): 923. CrossRef

Original Articles

Diagnostic Value of MDM2 and DDIT3 Fluorescence In Situ Hybridization in Liposarcoma Classification: A Single-Institution Experience: Junhun Cho, Seung Eun Lee, Yoon-La Choi; Korean J Pathol. 2012;46(2):115-122. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.115

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Abstract PDF

Background

The amplification of murine double minutes (MDM2) is the primary feature of well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS), while DDIT3 rearrangement is the main one of myxoid liposarcomas (MLPS). Our aim was to evaluate the added value of MDM2 amplification and DDIT3 rearrangement in making a diagnosis and classifying lipogenic tumors.

Methods

Eighty-two cases of liposarcoma and 60 lipomas diagnosed between 1995 and 2010 were analysed for MDM2 amplification and DDIT3 rearrangement using a fluorescence in situ hybridization (FISH). The subtypes of liposarcoma were reclassified according to the molecular results, whose results were reviewed with an analysis of the relevant histologic and immunohistochemical findings.

Results

One case of lipoma (1.67%) was reclassified as a WDLPS. Of the liposarcomas, 13.4% (16/82) were reclassified after the molecular testing. Five cases of MLPS were reclassified as four cases of DDLPS and one case of myxoid lipoma. Two cases of WDLPS were reclassified as one case of spindle cell lipoma and another case of myxofibrosarcoma. Four cases of DDLPS were reclassified as two cases of leiomyosarcoma, one case of angiomyolipoma and another case of fibroinflammatory lesion. Of the six cases of pleomorphic liposarcoma, five were reclassified as DDLPS.

Conclusions

In our series, a critical revision of diagnosis was found at a rate of 3.5% (5/142) after a review of the lipomatous lesions. The uses of molecular testing by MDM2 and DDIT3 FISH were valuable to make an accurate subtyping of liposarcomas as well as to differentiate WDLPS from benign lipomatous tumor.

Citations

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Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study
Naoki Kojima, Takashi Kubo, Taisuke Mori, Kaishi Satomi, Yuko Matsushita, Shintaro Iwata, Yasushi Yatabe, Koichi Ichimura, Akira Kawai, Hitoshi Ichikawa, Akihiko Yoshida
Virchows Archiv.2024; 484(1): 71. CrossRef
FISH Diagnostic Assessment of MDM2 Amplification in Liposarcoma: Potential Pitfalls and Troubleshooting Recommendations
Alessandro Gambella, Luca Bertero, Milena Rondón-Lagos, Ludovica Verdun Di Cantogno, Nelson Rangel, Chiara Pitino, Alessia Andrea Ricci, Luca Mangherini, Isabella Castellano, Paola Cassoni
International Journal of Molecular Sciences.2023; 24(2): 1342. CrossRef
Expression of CTAG1B clone EPR13780 versus DDIT3 gene rearrangement distinguishes myxoid liposarcoma from its mimics with detection of novel DDIT3 gene copy number variations
Marwa M. Abdelaziz, Hanan Y. Tayel, Amany Abdel-Bary, Omnia M. Badawy
Journal of Histotechnology.2022; 45(2): 56. CrossRef
Musculoskeletal Tumors
Amit Singla, David S. Geller
Pediatric Clinics of North America.2020; 67(1): 227. CrossRef
Vulvar Myxoid Liposarcoma, an Extremely Rare Diagnosis: A Case Report and Review of Literature
Ligia Redroban, Nelson Montalvo
International Journal of Gynecological Pathology.2019; 38(1): 17. CrossRef
Molecular updates in adipocytic neoplasms✰
Elizabeth G. Demicco
Seminars in Diagnostic Pathology.2019; 36(2): 85. CrossRef
Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas
Min Jeong Song, Kyung-Ja Cho, Jong-Seok Lee, Joon Seon Song
Applied Immunohistochemistry & Molecular Morphology.2017; 25(10): 712. CrossRef
FluorescenceIn SituHybridization forMDM2Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center
Khin Thway, Jayson Wang, John Swansbury, Toon Min, Cyril Fisher
Sarcoma.2015; 2015: 1. CrossRef

Prognostic Significance of Amplification of the c-MYC Gene in Surgically Treated Stage IB-IIB Cervical Cancer.: Tae Jung Kim, Ahwon Lee, Sung Jong Lee, Won Chul Lee, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang; Korean J Pathol. 2011;45(6):596-603.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.596

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Abstract PDF

BACKGROUND
Mutations of c-MYC have been described in cervical cancer. However, association between c-MYC gene status and its prognostic significance have not been clarified.
METHODS
Tissue microarray sections from 144 patients with stage IB-IIB cervical cancer treated by radical hysterectomy were analyzed by fluorescence in situ hybridization using a region-specific probe for c-MYC and a centromere-specific probe for chromosome 8.
RESULTS
Seventy five percent (108/144) of c-MYC gain and 6.9% (10/144) of c-MYC gene amplification were observed. c-MYC gene alteration was more frequently observed in squamous cell carcinoma than adenocarcinoma or adenosquamous carcinoma and were associated with low Ki67 labeling index (p=0.013). c-MYC amplification was not associated with clinicopathologic parameters except absence of bcl2 expression (p=0.048). Survival analysis revealed that patients with c-MYC amplification were significantly associated with higher risk of disease recurrence (p=0.007) and cancer related death (p=0.020). However, c-MYC gain was not associated with unfavorable outcome. Multivariate analysis proved c-MYC amplification as independent prognostic factors of shorter disease free survival and cancer-related death (p=0.028 and p=0.025, respectively).
CONCLUSIONS
c-MYC amplification, not gain, is an independent prognostic marker for shorter disease free and cancer specific survival in cervical cancer treated by radical hysterectomy.

Citations

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A Rare Case of Cutaneous Plasmacytosis in a Korean Male
Corey Georgesen, Meenal Kheterpal, Melissa Pulitzer
Case Reports in Pathology.2017; 2017: 1. CrossRef

Evaluation of the HPV ISH Assay in Cervical Cancer.: Jung Uee Lee, Jung Ha Shin, Jong Ok Kim, Yeong Jin Choi, Kyo Young Lee, Jong Sup Park, Won Chul Lee, Ahwon Lee; Korean J Pathol. 2010;44(5):513-520.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.513

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Abstract PDF

BACKGROUND
Human papillomavirus (HPV) infection can be detected by in situ hybridization (ISH), in which a punctate signal pattern indicates integrated HPV DNA and a diffuse pattern denotes the presence of episomal viral DNA. This study was conducted to evaluate the usefulness of an HPV ISH assay for invasive cervical cancer.
METHODS
The HPV ISH assay for high-risk HPV and immunohistochemical staining for p16(INK4a), p53, bcl-2, and Ki-67 were performed in a tissue microarray of 279 cervical cancers.
RESULTS
High-risk HPV ISH was positive in 194 (69.5%) of the samples. Punctate, diffuse, and mixed signal patterns were observed in 157 (56.3%), one (0.4%), and 36 cases (12.9%), respectively. Positive results in high-risk HPV ISH were associated with p16 and bcl-2 expression (p = 0.01 and p < 0.01, respectively). According to a Cox regression analysis, HPV infection and its surrogate immunohistochemical markers such as p16, bcl-2, and Ki-67 were not independent prognostic factors, but stage and grade were independent prognostic factors.
CONCLUSIONS
Our results confirm that an HPV ISH assay is reasonably sensitive for HPV infection and that it might be useful to identify integrated HPV DNA in formalin-fixed and paraffin-embedded specimens. Further study encompassing HPV type, E2/E6 ratio, and therapeutic modality is necessary to understand the clinical meaning of HPV status in cervical cancer.

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Prevalence of human papillomavirus in eyelid carcinoma among Koreans: a clinicopathological study
Min Kyu Yang, Namju Kim, Hokyung Choung, Ji Eun Kim, Sang In Khwarg
BMC Ophthalmology.2023;[Epub] CrossRef
Cervical cancer screening by molecular Pap‐transformation of gynecologic cytology
Shaikhali M Barodawala, Kirti Chadha, Vikas Kavishwar, Anuradha Murthy, Shamma Shetye
Diagnostic Cytopathology.2019; 47(5): 374. CrossRef
Prognostic Significance of Amplification of thec-MYCGene in Surgically Treated Stage IB-IIB Cervical Cancer
Tae-Jung Kim, Ahwon Lee, Sung-Jong Lee, Won-Chul Lee, Yeong-Jin Choi, Kyo-Young Lee, Chang Suk Kang
The Korean Journal of Pathology.2011; 45(6): 596. CrossRef

HER2 Status in Gastric Adenocarcinomas Assessed by Immunohistochemistry, Automated Silver-Enhanced In Situ Hybridization and Fluorescence In Situ Hybridization.: Aeri Kim, Jung Min Bae, Se Won Kim, Mi Jin Gu, Young Kyung Bae; Korean J Pathol. 2010;44(5):493-501.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.493

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Abstract PDF

BACKGROUND
Recently, many studies have focused on human epidermal growth factor receptor 2 (HER2) status in gastric cancer due to HER2-targeted therapy using trastuzumab. We investigated HER2 overexpression and amplification and their concordance rate in Korean gastric adenocarcinomas.
METHODS
Tissue microarrays were constructed with 232 gastric adenocarcinoma samples. We performed immunohistochemistry (IHC), silver-enhanced in situ hybridization (SISH) and fluorescence in situ hybridization (FISH) for HER2.
RESULTS
IHC was negative in 94.8% (218/232), equivocal in 1.7% (4/232) and positive in 3.5% (8/232) of cases. HER2 protein expression was heterogeneous in 75% (9/12) of IHC 2+/3+ cancers. Gene amplification was observed in 6.5% (15/230) by SISH and the same 15 cases were also FISH-positive. We observed HER2 amplification in 1.4%, 27.3%, 25%, and 100% of IHC 0, 1+, 2+, and 3+ gastric adenocarcinomas, respectively. The concordance rate between IHC and SISH results was 95.7%.
CONCLUSIONS
HER2 overexpression and amplification were less frequent in gastric adenocarcinomas than breast carcinomas. Compared to breast carcinoma, (1) there may be IHC-negative but gene amplification-positive cases for HER2 and (2) frequent intratumoral heterogeneity of IHC for HER2 in gastric adenocarcinomas.

Citations

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Epidemiologic Study of Human Epidermal Growth Factor Receptor 2 Expression in Advanced/Metastatic Gastric Cancer: an Assessment of Human Epidermal Growth Factor Receptor 2 Status in Tumor Tissue Samples of Gastric and Gastro-Esophageal Junction Cancer
Kyung Won Seo, Taeyong Jeon, Sewon Kim, Sung Soo Kim, Kwanghee Kim, Byoung-Jo Suh, Sunhwi Hwang, SeongHee Choi, Seungwan Ryu, Jae Seok Min, Young-Joon Lee, Ye Seob Jee, Hyeondong Chae, Doo Hyun Yang, Sang Ho Lee
Journal of Gastric Cancer.2017; 17(1): 52. CrossRef
Synopsis on Clinical Practice Guideline of Gastric Cancer in Korea: An Evidence-Based Approach
Jun Haeng Lee, Jae G. Kim, Hye-Kyung Jung, Jung Hoon Kim, Woo Kyoung Jeong, Tae Joo Jeon, Joon Mee Kim, Young Il Kim, Keun Won Ryu, Seong-Ho Kong, Hyoung Il Kim, Hwoon-Yong Jung, Yong Sik Kim, Dae Young Zang, Jae Yong Cho, Joon Oh Park, Do Hoon Lim, Eun S
The Korean Journal of Gastroenterology.2014; 63(2): 66. CrossRef
Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach
Jun Haeng Lee, Jae G. Kim, Hye-Kyung Jung, Jung Hoon Kim, Woo Kyoung Jeong, Tae Joo Jeon, Joon Mee Kim, Young Il Kim, Keun Won Ryu, Seong-Ho Kong, Hyoung-Il Kim, Hwoon-Yong Jung, Yong Sik Kim, Dae Young Zang, Jae Yong Cho, Joon Oh Park, Do Hoon Lim, Eun S
Journal of Gastric Cancer.2014; 14(2): 87. CrossRef

Automated Silver-enhanced In Situ Hybridization for Evaluation of HER2 Gene Status in Breast Carcinoma: Comparison with Fluorescence In Situ Hybridization and Immunohistochemistry.: Woo Jung Sung, Seok Ju Park, Mi Jin Gu, Young Kyung Bae; Korean J Pathol. 2010;44(1):28-34.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.28

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Abstract PDF

BACKGROUND
The human epidermal growth factor receptor 2 (HER2) is amplified in 20-25% of breast cancers. HER2 overexpression or amplification is associated with a worse clinical outcome and it can predict the benefit from anthracycline and anti-HER2 therapies. The HER2 status has usually been assessed by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) in clinical samples. A new silver-enhanced in situ hybridization (SISH) technique was recently introduced. Therefore we evaluated the usefulness of SISH for detecting HER2 amplification.
METHODS
Tissue microarrays (TMAs) were constructed with 144 invasive breast cancer tissue samples. We performed IHC, FISH and SISH for HER2 on the tissue sections from the TMAs and we interpreted the results according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. The concordant rates between the two different tests were calculated.
RESULTS
HER2 was overexpressed and amplified in 16.9%, 16.9%, and 18% of the cases by IHC, FISH and SISH, respectively. The concordant rates between IHC and FISH, IHC and SISH, and FISH and SISH were 95.1%, 95.7%, and 97.8%, respectively.
CONCLUSIONS
SISH can be an alternative test for evaluating HER2 amplification because the 97.8% concordance with FISH satisfies the ASCO/CAP requirement of > 95% concordance with an alternative validated method.

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Francesca Sanguedolce, Pantaleo Bufo
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The Prognostic Subgroups as Defined by the Patterns of Epstein-Barr Virus Infection in Patients with Hodgkin Lymphoma.: Ji Hyeon Roh, Seok Jin Kim, Won Seog Kim, Young Hyeh Ko; Korean J Pathol. 2010;44(1):22-27.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.22

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Abstract PDF: BACKGROUND
The purpose of this study was to investigate the prognostic significance of the Epstein-Barr virus (EBV) infected non-neoplastic lymphocytes in patients with Hodgkin lymphoma (HL).
METHODS
Seventy-seven cases of HL were evaluated by immunohistochemical analysis and EBV-encoded RNA in situ hybridization. The cases were divided into three groups according to the EBV status. EBV was negative in 48 cases (group 1), EBV was located in the Hodgkin/Reed-Sternberg (HRS) cells, but not in the non-neoplastic lymphocytes in 20 cases (26%) (group 2) and EBV was located in both the HRS cells and the non-neoplastic lymphocytes in 9 cases (12%) (group 3).
RESULTS
The groups differed with respect to the age distribution, the clinical presentation and the prognosis. The median ages were 30 (group 1), 47.5 (group 2) and 23 years (group 3) (p = 0.011). B symptoms (p = 0.007) and the histologic subtype of mixed cellularity classical HL (p = 0.001) were more common in the EBV-positive patients than in their EBV-negative counterparts. Two patients from group 3 had associated chronic EBV infection syndrome. The five-year survival rate was 97.56% in group 1, 75.76% in group 2 and 100% in group 3 (p = 0.0178).
CONCLUSIONS
HL with EBV located in both the HRS cells and the non-neoplastic lymphocytes is a distinct prognostic subgroup that has better survival than the HL with EBV located in only the HRS cells.

Case Report

Extramedullary B Lymphoblastic Crisis of CML, Presenting as a Leptomeningeal Tumor: A Case Report.: Hoiseon Jeong, Bongkyung Shin, Sook Young Bae, Sangho Lee, Youngjune Ryu, Hankyeom Kim, Insun Kim; Korean J Pathol. 2009;43(5):482-488.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.482

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Abstract PDF: We report here on a rare case of a patient who presented with an extramedullary B lymphoblastic crisis as an initial manifestation of chronic myelogenous leukemia (CML). A 71-year-old man visited the emergency room due to suddenly developed dysarthria and right side weakness. Emergency craniotomy was done under the presumptive diagnosis of subdural hemorrhage. During the operation, a poorly demarcated firm mass was identified in the leptomeningeal space. Microscopically, the majority of the tumor was composed of monotonous immature cells with blast morphology, and these cells were immunoreactive for TdT, CD34, CD10 and CD20, indicating the precursor B-cell phenotype. The peripheral area of the tumor consisted of myeloid cells in various stages of maturation, and these cells were reactive for myeloperoxidase, chloroacetate esterase, CD43 and CD15. FISH analysis using the LSI bcr-abl dual color probe showed gene fusion signals in both the B-lymphoblasts and myeloid cells. The peripheral blood and bone marrow findings were consistent with CML with no evidence of a blast crisis. Cytogenetic study of the bone marrow demonstrated the 46, XY, t(9;22)(q34;q11) chromosome. A diagnosis of extramedullary B lymphoblastic blast crisis in a patient with Philadelphia chromosome-positive CML was made. Despite treatment, the patient died 3 months after he was diagnosed.

Original Article

The EGFR Protein Expression and the Gene Copy Number Changes in Renal Cell Carcinomas.: Sangho Lee, Jungsuk An, Aeree Kim, Young Sik Kim, Insun Kim; Korean J Pathol. 2009;43(5):413-419.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.413

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Abstract PDF

BACKGROUND
The epidermal growth factor receptor (EGFR) is known to be involved in many tumor promoting activities. EGFR inhibition has been tried as a therapeutic modality in many human malignancies.
METHODS
The expression of EGFR protein and the gene copy number changes were studied in 135 clear cell carcinomas and 16 papillary renal cell carcinomas (RCCs), and these tumors were diagnosed between 1995 and 1997.
RESULTS
An EGFR protein expression (2+ and 3+) was found in 54.1% of the clear cell RCCs and in 43.8% of the papillary RCCs. In the clear cell RCCs, its expression was associated with male gender, the tumor size (> or =4 cm) and high T stages (T2 and T3), with statistical significance. Trisomy and polysomy of the EGFR gene were found in 27 (25.7%) and 40 (38.1%) of 105 clear cell RCCs, respectively. Trisomy and polysomy were correlated with an EGFR protein expression and a high clinical T stage, with statistical significance. Among 15 papillary RCCs, 13 tumors showed trisomy (86.7%) and one showed polysomy (6.7%). Amplification was not found in both the clear cell and papillary type RCCs.
CONCLUSIONS
A considerable numbers of RCCs showed an overexpression of EGFR protein and increased EGFR gene copy numbers, yet the clinical significance of conducting a FISH study in RCC patients seems to be limited.

Citations

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EGFR protein overexpression correlates with chromosome 7 polysomy and poor prognostic parameters in clear cell renal cell carcinoma
Gordana Đorđević, Koviljka Matušan Ilijaš, Ita Hadžisejdić, Anton Maričić, Blaženka Grahovac, Nives Jonjić
Journal of Biomedical Science.2012;[Epub] CrossRef

Case Report

Interfollicular Hodgkin's Lymphoma: A case report.: Lee So Maeng, Kyung Mee Kim, You Mee Kang, Chang Seok Kang, Sang In Shim; Korean J Pathol. 1995;29(6):804-806.

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Abstract PDF: An unusual pattern of focal involvement of lymph nodes by Hodgkin's disease is described using the name Interfollicular Hodgkin's Disease. It is characterized by florid reactive follicular hyperplasia which overshadows involvement of the interfollicular zones by Hodgkin's desease. The importance of interfollicular Hodgkin's disease rests on its misdiagnosis as a benign lesion. We report a case of interfollicular Hodgkin's disease in a 34-year-old female patient in the inguinal area. The lymph nodes showed reactive follicular hyperplasia. The focal interfollicular spaces were invaded by Hodgkin's disease. The Reed-Stemberg cells stained positively with CD15 and CD30 antibody in the immunohistochemical stain. An in situ hybridization study looking for EBV was negative in these R-S cells.

Original Article

Correlation between Transforming Growth Factor-beta and Procollagen III with Regenerative Activity in Acute Liver Injury, and the Effect of Prostaglandin E2.: Nam Hoon Cho, Chan Il Park; Korean J Pathol. 1996;30(5):367-387.

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Abstract PDF: Transforming growth factor-beta (TGF-beta) plays an important role in hepatic fibrogenesis. It is thought to inhibit regeneration of the hepatocytes. The aim of this present study was to clarify the correlation of TGF-beta, collagen type III (PIIINP) and the regenerating activity of hepatocytes, and the effect of prostaglandin E2 (PgE2) on them in acute liver injury. Two hundred and sixteen male Sprague-Dawley rats, weighing 200g on average, were divided into six experimental groups and two control groups; group I-CCl4 only administration, group II-partial hepatectomy(PH) only, group III-PH following CCl4 administration, group IV-olive oil only administration, group V-sham operation, group VI-CCl4 administration with pretreatment of PgE2, group VII- PH with pretreatment of PgE2, and group VIII- PH following CCl4 administration with pretreatment of PgE2. Five rats were sacrificed at 12, 24, 36, 48, 96 and 168 hours after the administration of CCl4 or PH in each experimental group. The liver was tested with immunohistochemical stain for proliferating cell nuclear antigen (PCNA) and in situ hybridization for TGF-beta. Radioimmunoassay for serum PIIINP was also performed. The results were as follows: TGF-beta was expressed mainly in the perisinusoidal cells and periportal mesenchymal cells. The TGF-beta positive cells were most numerous in the combined group of CCl4 plus PH. TGF-beta expression tended to have an inverse relation, with the PCNA index in all experimental groups. The PCNA index was highest in the CCl4 only group and lowest in the combined group of CCl4 plus PH. The PH only group showed a peak PCNA index at 48 hours. In the CCl4 only group and the combined group of CCl4 plus PH, serum PIIINP appeared to increase at 12 hours or more after the expression of hepatic TGF-beta. Pretreatment of PgE2 revealed that TGF-beta precipitously disappeared at 48-96 hours after insult. PgE2 influenced the vanishing period, not the emerging time of TGF-beta and had a remarkable effect on the amount of TGF-beta especially in the PH following CCl4 administration group, which resulted in significant accentuation of PCNA indices. In conclusion, PH of the prior injured liver induces a marked increase of TGF-beta followed by a significant suppression of regeneration of the remaining liver, and PgE2 overtly suppresses the expression of TGF-beta.

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