HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival

Abstract

The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.

HER-2/neu Overxpression in Esophageal Squamous Cell Carcinoma (ESCC) and Its Correlation with Patient’s Clinicopathological Features

“…no significant association between gender and age with HER2/neu overexpression in patients with ESCC which supports the results of previous studies (19,20). In this study, overall HER2 expression in ESCC patients without considering IHC scores was (33 patients) 51.5% which seems to be high compared to previous reports (21)(22)(23). The reported rate of HER2 gene amplification vary from 6.5% -30% (4,24,25).…”

Hsp90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino-17-demethoxygeldanamycin

“…All cases in the study by Faried et al (2004) were squamous cell carcinomas, whereas our study included both squamous cell carcinomas and adenocarcinomas, however, the squamous cancers dominating (65%) and all demonstrating a clear expression of Hsp90. These contradictory results might be explained by differences in stages of disease, treatment modalities as well as different populations, which may have different expressions of oncogenic proteins as seen for HER2 in oesophageal cancer (Lam et al, 1998;Dreilich et al, 2006). Furthermore, a relatively higher expression of Hsp90 was found in squamous cell carcinomas compared with adenocarcinomas, a finding that has never been reported before.…”

“…The immunostaining was performed according to the method published by Dreilich et al (2006). Samples with a known expression of Hsp90 (HeLa cells) were used as positive control.…”

Esophageal and Esophagogastric Junction Cancers

“…42 For patients with unresectable locally advanced, recurrent, or metastatic adenocarcinoma of the esophagus or EGJ, assessment for tumor HER2-neu overexpression should be performed using immunohistochemistry and/or fluorescence in situ hybridization (FISH), following the 4-tier HER2-neu scoring system used in the ToGA trial (see page 844). 49,50 In cases showing weak to moderate complete, basolateral, or lateral membranous reactivity in more than 10% of cancer cells (immunohistochemistry score = 2), the HER2-neu overexpression is considered equivocal and should be confirmed with immunohistochemistry and FISH.…”