HER-family receptor dynamics in esophageal cancer.

Stap, L.D. (2014) HER-family receptor dynamics in esophageal cancer. thesis, Medicine.

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Abstract

Background: Worldwide, esophageal cancer occurs at a rate of approximately half a million cases each year. In the last 2 decades, the incidence of EC has increased almost 3-fold in the Netherlands. HER2 is part of the HER-family oncogenes and is overexpressed in 1–25% of the esophageal carcinomas. It can be targeted by trastuzumab in metastatic EC patients. Unfortunately many patients will develop resistance to trastuzumab. In this study we retrospectively investigated the dynamics of HER2 after chemoradiotherapy (CRT) and the correlation with response to treatment and survival. To understand more about trastuzumab resistance mechanisms, the dynamics of the HER-family receptors after long-term trastuzumab exposure were investigated. Material and methods: Biopsies and subsequent resection specimens from 129 EC patients were collected. Three groups were distinguished: patients who have had surgery (n=33), surgery and CRT(n=75) or surgery, CRT and panitumumab (=monoclonal antibody against EGFR) (n=21). HER2 assessment was carried out by immunohistochemistry (IHC). The dynamics of HER-family receptors after trastuzumab exposure were investigated in a HER2 positive cell line (OE19) by immunofluorescence microscopy. Cells were cultured for 9 months in media with or without 1μg/ml trastuzumab. Results/conclusion: CRT does significantly alternate HER2 expression level (P=0.038). HER2 status was concordant between biopsy and resection specimen in 93.9% of the cases. Combined analysis of the HER2 status of the biopsy and resection specimen relatively increased the HER2+ cases with 18.5%. There was a positive trend in overall survival in HER2+ cases, although not significant (P=0.061). Long-term trastuzumab exposure led upregulation of EGFR and HER3 in the OE19 cell line, which is likely to be an important factor in the development of trastuzumab resistance.

Item Type:	Thesis (Thesis)
Supervisor name:	Nijholt, Dr. I.M.
Supervisor name:	Laarhoven, Prof. dr. H.W.M. van and Medical Oncology and Academic Medical Centre Amsterdam
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:40
Last Modified:	25 Jun 2020 10:40
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/162

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