Journal of Pathology and Translational Medicine

Original Articles

HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient: Dang Anh Thu Phan, Vu Thien Nguyen, Thi Ngoc Ha Hua, Quoc Dat Ngo, Thi Phuong Thao Doan, Sao Trung Nguyen, Anh Tu Thai, Van Thanh Nguyen; J Pathol Transl Med. 2017;51(4):396-402. Published online June 19, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.24

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Background
Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab.
Methods
We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated.
Results
In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+.
Conclusions
HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

Citations

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Identifying HER2 from serum‐derived exosomes in advanced gastric cancer as a promising biomarker for assessing tissue HER2 status and predicting the efficacy of trastuzumab‐based therapy
Qian Li, Minzhi Lv, Lihua Lv, Nida Cao, Aiguang Zhao, Jiayan Chen, Xi Tang, Rongkui Luo, Shan Yu, Yan Zhou, Yuehong Cui, Wei Guo, Tianshu Liu
Cancer Medicine.2023; 12(4): 4110. CrossRef
A study of human epidermal growth factor receptor 2 overexpression by immunohistochemistry in patients with gastric adenocarcinoma
Rafid A. Abood, Saad Alomar, Sawsan S. Alharoon
Journal of Public Health in Africa.2023;[Epub] CrossRef
Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
Hideki Yamaguchi, Yuko Nagamura, Makoto Miyazaki
Cancers.2022; 14(15): 3750. CrossRef
Cell differentiation trajectory predicts patient potential immunotherapy response and prognosis in gastric cancer
Renshen Xiang, Yuping Rong, Yuhang Ge, Wei Song, Jun Ren, Tao Fu
Aging.2021; 13(4): 5928. CrossRef
Identification of stem cell-related subtypes and risk scoring for gastric cancer based on stem genomic profiling
Renshen Xiang, Wei Song, Jun Ren, Jing Wu, Jincheng Fu, Tao Fu
Stem Cell Research & Therapy.2021;[Epub] CrossRef
Oncogenic signaling pathways associated with immune evasion and resistance to immune checkpoint inhibitors in cancer
Yoshie Kobayashi, Seung-Oe Lim, Hirohito Yamaguchi
Seminars in Cancer Biology.2020; 65: 51. CrossRef
Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer
Yu-Chang Chuang, Hsin-Yi Wu, Yu-Ling Lin, Shey-Cherng Tzou, Cheng-Hsun Chuang, Ting-Yan Jian, Pin-Rong Chen, Yuan-Ching Chang, Chi-Hsin Lin, Tse-Hung Huang, Chao-Ching Wang, Yi-Lin Chan, Kuang-Wen Liao
Biological Procedures Online.2018;[Epub] 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.

Citations

Citations to this article as recorded by

HER2 assessment by silverin situhybridization: where are we now?
Francesca Sanguedolce, Pantaleo Bufo
Expert Review of Molecular Diagnostics.2015; 15(3): 385. CrossRef
Diagnostic Effectiveness of PCR-based Tests DetectingBRAFMutation for Treating Malignant Melanoma: A Systematic Review
Hae-Won Shin, Ryeo-Jin Ko, Min Lee, Hee-Young Bang, Kye-Chul Kwon, Jong-Woo Park, Sun-Hoe Koo
Laboratory Medicine Online.2014; 4(4): 203. CrossRef
Effectiveness of Silver-enhanced In Situ Hybridization for Evaluating HER2 Gene Status in Invasive Breast Carcinoma: A Comparative Study
Youngseok Lee, Youngjoon Ryu, Hoiseon Jeong, Hyeyoon Chang, Younghye Kim, Aeree Kim
Archives of Medical Research.2012; 43(2): 139. CrossRef
HER2 Status by Standardized Immunohistochemistry and Silver-EnhancedIn SituHybridization in Korean Breast Cancer
Young Kyung Bae, Gyungyub Gong, Jun Kang, Ahwon Lee, Eun Yoon Cho, Ji Shin Lee, Kwang-Sun Suh, Dong Wha Lee, Woo Hee Jung
Journal of Breast Cancer.2012; 15(4): 381. CrossRef
Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting NormalHER2andTOP2AStatus
Aeri Kim, Hyung Chan Shin, Young Kyung Bae, Min Kyoung Kim, Su Hwan Kang, Soo Jung Lee, Eun Hee Lee
Journal of Breast Cancer.2012; 15(1): 24. CrossRef
HER2-Positive Breast Carcinomas with Co-amplification or Gain of Chromosome 17 Centromere Locus: Report of Three Cases and an Impact on HER2 Testing
Hyeong Chan Shin, Young Kyung Bae, Aeri Kim, Seok Ju Park
The Korean Journal of Pathology.2011; 45(6): 665. CrossRef
The Effectiveness of SilverIn SituHybridization in Patients with Breast Cancer: A Systematic Review
Sunyoung Jang, Seon-Heui Lee, Soojin Kim, You-Kyoung Lee, Young-Hyuck Im, Wonshik Han, Hee-Sook Park
Journal of Breast Cancer.2011; 14(Suppl 1): S1. CrossRef
Clinical and health economic outcomes of alternative HER2 test strategies for guiding adjuvant trastuzumab therapy
James A Lee, Megan Shaheen, Thomas Walke, Matt Daly
Expert Review of Pharmacoeconomics & Outcomes Research.2011; 11(3): 325. CrossRef
HER2 expression in breast cancer: Comparisons of fluorescence in situ hybridization and silver in situ hybridization, and immunohistochemical staining using monoclonal antibody and polyclonal antibody
Jung Sik Jang, Eun Jeong Jang, Ji‐Young Park
Basic and Applied Pathology.2010; 3(4): 115. CrossRef
HER2Status in Gastric Adenocarcinomas Assessed by Immunohistochemistry, Automated Silver-EnhancedIn SituHybridization and FluorescenceIn SituHybridization
Aeri Kim, Jung Min Bae, Se Won Kim, Mi Jin Gu, Young Kyung Bae
The Korean Journal of Pathology.2010; 44(5): 493. CrossRef

Immunocytochemical Detection of Pneumocystis Carinii in Bronchoalveolar Lavage .: Kun Young Kwon, Seung Che Cho, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Chung Sook Kim; Korean J Cytopathol. 1997;8(1):27-34.

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Abstract PDF: Pneumocystis carinii is an established cause of pulmonary infections in immuno- compromised hosts. Several cytological stains, such as Papanicolaou, Gomori methenamine silver(GMS) and Diff-Quik have been used for detection of the organism, but occasionally can be laborious and, due to a degree of nonspecificity, may be misleading. We evaluated the diagnostic utility of immunocytochemical stains that recognize P. carinii in bronchoalveolar lavage from experimentally induced P. carinii pneumonia rats(n=15). In addition to routine stains for diagnosis by morphologic recognition of P. carinii on Papanicolaou, GMS and Diff-Quik stains, bronchoalveolar lavage samples were reacted with immunocytochemical stains using monoclonal antibodies(MAB) 092 and 902. In bronchoalveolar lavage P. carinii organisms were detected in 9 of 10 cases (90%) using each MAB 092 and 902, whereas GMS and Diff-Quik stains demonstrated P. carinii in 13(86%) and 11(73%) of 15 cases respectively. In lung tissue specimens(n=15) P. carinii organisms were well identified on GMS stain and immunohistochemical stains using MAB 092 and 902 in all cases. We believe that the immunocytochemical staining using MAB 092 and/or 902 is a very useful and diagnostic tool in addition to GMS and Diff-Quik stain to detect P. carinii organisms in bronchoalveolar lavage.

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