Akihiko Yoshizawa1, Shinji Sumiyoshi2, Makoto Sonobe3, Masashi Kobayashi3, Takeshi Uehara4, Masakazu Fujimoto2, Tatsuaki Tsuruyama2, Hiroshi Date3, Hironori Haga2. 1. Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan; Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. Electronic address: akyoshi@shinshu-u.ac.jp. 2. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. 3. Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan. 4. Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan.
Abstract
OBJECTIVES: While novel anti-human epidermal growth factor receptor 2 (HER2) agents have recently been developed, no definite criteria have been proposed as indications for the use of these agents in patients with lung cancer. Here, we tested HER2 alterations by using four methods and explored the concordance of these methods to improve our understanding of the accuracy of HER2 testing methods. MATERIALS AND METHODS: We analyzed HER2 protein expression by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH) and dual in situ hybridization (DISH) by using a tissue microarray comprising lung adenocarcinoma specimens from 243 consecutive patients. The presence of mutations in the EGFR, KRAS, and HER2 genes were also determined. RESULTS: Positive IHC (score 3+) was observed in six cases (2.5%). Amplification of HER2 was observed in five cases (2.1%) by FISH and in nine cases (3.7%) by DISH. HER2 expression by IHC and gene amplification by FISH were significantly associated (P<0.001). The overall concordance between FISH and DISH by amplification status was 96.7% (P<0.001). One hundred nine tumors (49.9%) had EGFR mutations, 25 (11.2%) had KRAS mutations, and six (2.7%) had HER2 mutations. All of these mutations were mutually exclusive. Cases having HER2 mutations were positively correlated with cases having HER2 amplification (P<0.001). Two of six cases with HER2 mutations showed amplifications by FISH and DISH tests. CONCLUSION: HER2 protein overexpression, gene amplification, and gene mutations appeared to be uncommon in lung adenocarcinoma. Cases with HER2 mutations tended to show HER2 gene amplification. The results indicated that HER2 gene amplification and mutations should be tested to determine whether patients are eligible for administration of new anti-HER2 agents. In addition, DISH was better than FISH for detection of cases with HER2 amplification.
OBJECTIVES: While novel anti-humanepidermal growth factor receptor 2 (HER2) agents have recently been developed, no definite criteria have been proposed as indications for the use of these agents in patients with lung cancer. Here, we tested HER2 alterations by using four methods and explored the concordance of these methods to improve our understanding of the accuracy of HER2 testing methods. MATERIALS AND METHODS: We analyzed HER2 protein expression by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH) and dual in situ hybridization (DISH) by using a tissue microarray comprising lung adenocarcinoma specimens from 243 consecutive patients. The presence of mutations in the EGFR, KRAS, and HER2 genes were also determined. RESULTS: Positive IHC (score 3+) was observed in six cases (2.5%). Amplification of HER2 was observed in five cases (2.1%) by FISH and in nine cases (3.7%) by DISH. HER2 expression by IHC and gene amplification by FISH were significantly associated (P<0.001). The overall concordance between FISH and DISH by amplification status was 96.7% (P<0.001). One hundred nine tumors (49.9%) had EGFR mutations, 25 (11.2%) had KRAS mutations, and six (2.7%) had HER2 mutations. All of these mutations were mutually exclusive. Cases having HER2 mutations were positively correlated with cases having HER2 amplification (P<0.001). Two of six cases with HER2 mutations showed amplifications by FISH and DISH tests. CONCLUSION:HER2 protein overexpression, gene amplification, and gene mutations appeared to be uncommon in lung adenocarcinoma. Cases with HER2 mutations tended to show HER2 gene amplification. The results indicated that HER2 gene amplification and mutations should be tested to determine whether patients are eligible for administration of new anti-HER2 agents. In addition, DISH was better than FISH for detection of cases with HER2 amplification.
Authors: Kami E Chiotti; Daniel J Kvitek; Karen H Schmidt; Gregory Koniges; Katja Schwartz; Elizabeth A Donckels; Frank Rosenzweig; Gavin Sherlock Journal: Genomics Date: 2014-11-01 Impact factor: 5.736
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Authors: Ting-Yuan David Cheng; Amy K Darke; Mary W Redman; Gary R Zirpoli; Warren Davis; Rochelle Payne Ondracek; Wiam Bshara; Angela R Omilian; Robert Kratzke; Mary E Reid; Julian R Molina; Jill M Kolesar; Yuhchyau Chen; Robert M MacRae; James Moon; Philip Mack; David R Gandara; Karen Kelly; Regina M Santella; Kathy S Albain; Christine B Ambrosone Journal: J Natl Cancer Inst Date: 2018-07-01 Impact factor: 13.506