Comparison of intratumoral heterogeneity of HER2 expression between primary tumor and multiple organ metastases in gastric cancer: Clinicopathological study of three autopsy cases and one resected case

Autor: Takuya Saito, Yasushi Yatabe, Hideo Tanaka, Hayao Nakanishi, Kohei Shitara, Yuichi Ito, Noriko Saito, Yuzuru Ikehara, Keigo Yamamichi, Chihiro Kondo
Rok vydání: 2015
Předmět:
Zdroj: Pathology International. 65:309-317
ISSN: 1320-5463
DOI: 10.1111/pin.12290
Popis: Intratumoral heterogeneity of HER2 expression in the metastatic foci of HER2-positive advanced gastric cancer remains unclear. In this study, we compared HER2 expression between primary and metastatic tumors in HER2-positive three autopsied cases and one resected case with multiple organ metastases by immunohistochemistry (IHC) and dual color in situ hybridization (DISH). All four cases judged positive (IHC3+) at the primary tumor tissues showed varying HER2 gene amplification (GA) status. One homogeneously HER2-positive autopsied case (Case 1) and one intratumorally heterogeneous positive resected case (Case 2) with high GA showed a homogeneous positive staining pattern in all the metastatic foci. One heterogeneously HER2-positive autopsied case (Case 3) with low GA showed a partially heterogeneous HER2 staining pattern in all the metastatic foci. In contrast, one heterogeneously HER2-positive autopsied case (Case 4) with equivocal GA showed a completely heterogeneous HER2 staining pattern in the metastatic foci. These results indicate that HER2-positive gastric cancers with low to high GA at the primary tumor show substantially homogeneous HER2 overexpression in the metastatic foci, whereas HER2-positive gastric cancers with equivocal GA expressed HER2 heterogeneously within the metastatic tumor, suggesting that metastatic foci of the latter HER2-positive cases would be potentially resistant to trastuzumab.
Databáze: OpenAIRE