Association between HER2 status in gastric cancer and clinicopathological features: a retrospective study using whole-tissue sections

Abstract

BackgroundGastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. Trastuzumab was recently approved for metastatic or locally advanced carcinomas arising in the stomach or in the gastroesophageal junction in patients with HER2-positive tumors. However, data on the frequency of HER2-positive cases among Brazilian patients are limited. Our aim was to characterize HER2 protein and gene status in a series of Brazilian patients with gastric cancer and to evaluate its association with clinicopathological data.MethodsHistological slides from 124 primary gastrectomies were reviewed and their pathological reports were retrieved from the files at a Brazilian university hospital. Automated immunohistochemistry for HER2 was performed on whole-tissue sections from each tumor. HER2-equivocal cases by immunohistochemistry were submitted to automated dual in situ hybridization for gene amplification evaluation. HER2 status was confronted with clinicopathological parameters in order to assess statistically significant associations.ResultsImmunohistochemistry analysis revealed that 13/124 cases (10.5 %) were HER2 positive (3+), 10/124 cases (8.1 %) were equivocal (2+) and 101/124 cases (81.4 %) were negative, being 7 cases 1+. None of the equivocal cases showed gene amplification. The overall HER2 positivity rate was 10.5 %. There was an association between HER2 expression and Laurén’s intestinal histological subtype (P = 0.048), well to moderately differentiated tumors (P = 0.004) and presence of lymphovascular invasion (P = 0.031). No association was found between HER2 status and tumor topography.ConclusionsConfronted with data published by other authors, the lower percentage of HER2-positive cases found in our series might be partially explained by the lower frequency of tumors arising at the gastroesophageal junction in comparison with distal gastric carcinomas in Brazilian patients. This could also account for the lack of statistically significant association between HER2 status and tumor topography in our study.

Relationship Between 18F-FDG PET/CT Findings and HER2 Expression in Gastric Cancer

“…SUV max was significantly lower in the HER2-positive group than in the HER2-negative group. Our data also demonstrated that HER2 expression is more common in well-or moderately differentiated adenocarcinoma than in poorly differentiated adenocarcinoma; this finding is consistent with the findings of previous studies (20)(21)(22). In addition, well-or moderately differentiated adenocarcinoma had significantly lower 18 F-FDG uptake than did poorly differentiated adenocarcinoma, partly explaining why patients with HER2 expression had a low SUV max (excluding signet-ring cell carcinoma from the analysis).…”

Study of HER-2/neu status in adenocarcinoma of stomach and gastroesophageal junction

“…The HER-2 positivity rate in our study is 10.99% which was comparable to several other studies like those conducted by Laboisseire et al 13 The methodology adopted by Sekaran et al was similar to that of our study. 17 However, they reported positive results in 44.2%.…”

“…All the HER-2 positive cases in our study showed intestinal type of histology with significant correlation (p=0.025) similar to the studies conducted by Rajagopal et al 20 Few studies, like those conducted by Laboisseire et al showed that in addition to the intestinal type, few cases with mixed type of histology also showed HER-2 positivity. 13 Studies by Figueroa-Barojas et al, Sekaran et al revealed no correlation between the two (p>0.05). 17,22 In our study, 25% of the grade-I tumors and 14.29% of the grade-II tumors were HER-2 positive.…”

Human epidermal growth factor receptor 2 (HER-2) status evaluation in advanced gastric cancer using immunohistochemistry versus silver in situ hybridization

“…In that study, elevated carcinoembryonic antigen levels, pulmonary metastasis, and distant lymph node metastasis have also emerged as significant predictors. Laboissiere et al identified intestinal histological subtype, histologic grade, and the presence of lymphovascular invasion as significant predictors of HER-2 positivity in gastric cancer [12]. In a study from Japan, intestinal type, absence of peritoneal metastasis, and hepatic metastasis were significant independent factors related to HER-2 positivity [13].…”