HER2 overexpression in gastric and esophageal adenocarcinoma: a clinicopathological and diagnostics analysis.

Koopman, T. (2013) HER2 overexpression in gastric and esophageal adenocarcinoma: a clinicopathological and diagnostics analysis. thesis, Medicine.

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Abstract

Background: The HER2/neu (Human Epidermal growth factor Receptor 2/neu) oncogene shows overexpression in 15-30% of gastric and esophageal adenocarcinoma. Trastuzumab was recently shown to provide a survival benefit in HER2 positive patients with advanced gastric and gastro-esophageal junction cancer. The need is increasing for diagnostic centers and pathologists capable of gastro-esophageal HER2 diagnostics. A standardized modified scoring system was recently introduced for gastro-esophageal HER2 scoring. Primary tumor classification of gastric or esophageal cancer changed, with the introduction of the 7th TNM (tumor, node, metastasis) edition of Classification of Malignant Tumours of the UICC (Union of International Cancer Control). Patients and methods: Tumor samples of 323 patients diagnosed with invasive gastric or esophaeal adenocarcinoma between 2004 and 2011 in the Deventer Hospital were collected. HER2 status was determined using immunohistochemistry (IHC) followed by chromogenic in situ hybridization (CISH) in samples scored equivocal or HER2 positive. IHC 3+ or IHC 2+/CISH positive tumors were considered HER2 positive. Association between clinicopathological variables and HER2 positivity was analyzed. A comparison was made between the 6th and 7th TNM edition on classifying gastric or esophageal primary tumors. Inter-observer variability on IHC scoring using the currently standard modified HER2 scoring system was determined among three pathologists and the scoring system was validated. Additionally, HER2 positivity and survival rates were analyzed in a subgroup of 46 patients with advanced disease receiving the currently recommended palliative triplet chemotherapy consisting of a fluoropyrimide, a platinum compound and an anthracyclin, without trastuzumab. Results: We found HER2 positive disease in 50 of 323 patients (15.6%). In univariate and multivariate logistic models, HER2 positivity rates were significantly higher in esophageal primary tumors (esophageal 25% vs. gastric 7.4%) and in intestinal histological tumor type (intestinal 24.3% vs. diffuse or mixed 11.5%). Using the 7th TNM edition, many tumors previously classified as gastric cancer are now classified as esophageal cancer (30.5% of all tumors in this study). Inter-observer agreement on IHC scoring was good (κ = 0.78) with higher levels of disagreement found in diffuse or mixed tumor type and in weak to moderate stained IHC samples (2+). The HER2 scoring system was found to be an excellent method to establish HER2 status. In the triplet chemotherapy subgroup, no significant difference in survival rates was found between HER2 positive and HER2 negative patients. Conclusions: HER2 positivity occurs in 15.6% of invasive gastro-esophageal adenocarcinoma in Western patients, with positivity rates varying depending on primary tumor location and histological tumor type. The currently used standardized HER2 scoring system is an excellent, clinically applicable method to establish HER2 status in appropriately trained pathologists. Further studies are needed on HER2 status in advanced disease patients receiving the recommended palliative triplet chemotherapy.

Item Type:	Thesis (Thesis)
Supervisor name:	Imholz, Dr. A.L.T. and Deventer Hospital and Internal Medicine
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:55
Last Modified:	25 Jun 2020 10:55
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1611

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