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.
Highlights
Gastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse
22.1 % accounts for more than double the amount of positive tumors we found in our series, the ToGA trial HER2 positivity screening criteria included all cases with protein expression by IHC (3+ and 2+ cases) or gene amplification by in situ hybridization (ISH) alone
More detailed data concerning HER2 testing in the ToGA study has been recently published revealing that precisely 610 cases out of 3,665 tumor samples (16.6 %) were considered HER2 positive, by either scoring IHC 3+ or IHC 2+ with gene amplification by fluorescence in situ hybridization (FISH) [30]
Summary
Gastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. 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. About one million new cases of gastric cancer (GC) are estimated to occur each year in the world, corresponding to 8 % of all cancer diagnoses globally [1, 2]. Treatment options for GC are generally limited, since it is usually diagnosed at an advanced stage of disease and, the five-year survival rate is consistently low, around 20 % in most parts of the world [2, 5]. Overexpression of the HER2 protein, a product of a proto-oncogene situated at chromosome 17, has been associated with carcinogenesis and tumor progression of breast, ovary, salivary glands, prostate and gastrointestinal tract cancers [9]
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