Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas

被引:76
作者
Cho, Eun Yoon [1 ]
Park, Kyeongmee [2 ]
Do, Ingu [3 ]
Cho, Junhun [1 ]
Kim, Jiyun [1 ]
Lee, Jeeyun [4 ]
Kim, Seonwoo [5 ]
Kim, Kyoung-Mee [1 ]
Sohn, Tae Sung [6 ]
Kang, Won Ki [4 ]
Kim, Sung [6 ]
机构
[1] Sungkyunkwan Univ, Dept Pathol, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea
[2] Inje Univ, Sanggye Paik Hosp, Dept Pathol, Seoul, South Korea
[3] Sungkyunkwan Univ, Sch Med, Samsung Canc Res Inst, Seoul 135710, South Korea
[4] Sungkyunkwan Univ, Sch Med, Dept Internal Med, Seoul 135710, South Korea
[5] Samsung Med Ctr, Samsung Biomed Res Inst, Dept Biostat, Seoul, South Korea
[6] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul 135710, South Korea
关键词
Amplification; ERBB2; gastric; immunohistochemistry; metastatic; primary; HELICOBACTER-PYLORI INFECTION; IN-SITU HYBRIDIZATION; C-ERBB-2; PROTEIN; GENE STATUS; PROGNOSTIC-SIGNIFICANCE; HER2; EXPRESSION; BREAST-CANCER; OVEREXPRESSION; AMPLIFICATION; TUMOR;
D O I
10.1038/modpathol.2012.205
中图分类号
R36 [病理学];
学科分类号
100103 [病原生物学];
摘要
Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be performed in both primary and distant metastatic sites.
引用
收藏
页码:677 / 684
页数:8
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