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Expression and prognostic significance of human epidermal growth factor receptors 1, 2 and 3 in oesophageal and gastric adenocarcinomas preneoadjuvant and postneoadjuvant treatment

Hedner, Charlotta LU ; Borg, David LU ; Nodin, Björn LU ; Karnevi, Emelie LU ; Jirström, Karin LU and Eberhard, Jakob LU (2018) In Journal of Clinical Pathology 71(5). p.451-462
Abstract

AIMS: Neoadjuvant treatment has now become the standard of care for oesophageal and gastric cancer. The aim of this study was to investigate the influence of neoadjuvant therapy on the expression of human epidermal growth factor receptor 1 (HER1/EGFR), HER2 and HER3, in oesophageal and gastric adenocarcinoma.

METHODS: Immunohistochemical expression of EGFR, HER2 and HER3 was examined and compared in pretreatment biopsies, post-treatment surgical resection specimens and metastases in a retrospective cohort of 166 patients with adenocarcinoma of the oesophagus or stomach. The relationship between expression of the investigative markers and histopathological response to neoadjuvant treatment, overall survival (OS) and recurrence free... (More)

AIMS: Neoadjuvant treatment has now become the standard of care for oesophageal and gastric cancer. The aim of this study was to investigate the influence of neoadjuvant therapy on the expression of human epidermal growth factor receptor 1 (HER1/EGFR), HER2 and HER3, in oesophageal and gastric adenocarcinoma.

METHODS: Immunohistochemical expression of EGFR, HER2 and HER3 was examined and compared in pretreatment biopsies, post-treatment surgical resection specimens and metastases in a retrospective cohort of 166 patients with adenocarcinoma of the oesophagus or stomach. The relationship between expression of the investigative markers and histopathological response to neoadjuvant treatment, overall survival (OS) and recurrence free survival (RFS) was analysed.

RESULTS: Conversion of protein expression between pretreatment biopsy and post-treatment surgical resection was seen in 4.6% of the cases for EGFR, 5.9% for HER2% and 19.4% for HER3. Histopathological response to neoadjuvant treatment was significantly and stepwise associated with OS and RFS . High HER3 protein expression in post-treatment surgical resection specimens was significantly associated with a prolonged OS in univariable analysis (HR=0.39; 95% CI 0.17 to 0.93), but did not remain significant in multivariable analysis. Expression of EGFR and HER2 in post-treatment surgical resection specimens was not prognostic. No correlation between pretreatment HER-protein expression and histopathological response was seen.

CONCLUSIONS: The results from this study underscore the need for further studies on the influence of neoadjuvant treatment on biomarker expression, as this may influence treatment strategy as well as prognosis. Histopathological response is validated as a useful prognostic factor.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
histopathology, immunohistochemistry, in situ hybridisation, oesophagus, stomach
in
Journal of Clinical Pathology
volume
71
issue
5
pages
12 pages
publisher
BMJ Publishing Group
external identifiers
  • scopus:85046048227
ISSN
1472-4146
DOI
10.1136/jclinpath-2017-204774
language
English
LU publication?
yes
id
b5ab56de-7bc8-45c6-bfb8-9121e45f41a1
date added to LUP
2018-05-07 15:02:06
date last changed
2019-02-20 11:16:37
@article{b5ab56de-7bc8-45c6-bfb8-9121e45f41a1,
  abstract     = {<p>AIMS: Neoadjuvant treatment has now become the standard of care for oesophageal and gastric cancer. The aim of this study was to investigate the influence of neoadjuvant therapy on the expression of human epidermal growth factor receptor 1 (HER1/EGFR), HER2 and HER3, in oesophageal and gastric adenocarcinoma.</p><p>METHODS: Immunohistochemical expression of EGFR, HER2 and HER3 was examined and compared in pretreatment biopsies, post-treatment surgical resection specimens and metastases in a retrospective cohort of 166 patients with adenocarcinoma of the oesophagus or stomach. The relationship between expression of the investigative markers and histopathological response to neoadjuvant treatment, overall survival (OS) and recurrence free survival (RFS) was analysed.</p><p>RESULTS: Conversion of protein expression between pretreatment biopsy and post-treatment surgical resection was seen in 4.6% of the cases for EGFR, 5.9% for HER2% and 19.4% for HER3. Histopathological response to neoadjuvant treatment was significantly and stepwise associated with OS and RFS . High HER3 protein expression in post-treatment surgical resection specimens was significantly associated with a prolonged OS in univariable analysis (HR=0.39; 95% CI 0.17 to 0.93), but did not remain significant in multivariable analysis. Expression of EGFR and HER2 in post-treatment surgical resection specimens was not prognostic. No correlation between pretreatment HER-protein expression and histopathological response was seen.</p><p>CONCLUSIONS: The results from this study underscore the need for further studies on the influence of neoadjuvant treatment on biomarker expression, as this may influence treatment strategy as well as prognosis. Histopathological response is validated as a useful prognostic factor.</p>},
  author       = {Hedner, Charlotta and Borg, David and Nodin, Björn and Karnevi, Emelie and Jirström, Karin and Eberhard, Jakob},
  issn         = {1472-4146},
  keyword      = {histopathology,immunohistochemistry,in situ hybridisation,oesophagus,stomach},
  language     = {eng},
  month        = {05},
  number       = {5},
  pages        = {451--462},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Clinical Pathology},
  title        = {Expression and prognostic significance of human epidermal growth factor receptors 1, 2 and 3 in oesophageal and gastric adenocarcinomas preneoadjuvant and postneoadjuvant treatment},
  url          = {http://dx.doi.org/10.1136/jclinpath-2017-204774},
  volume       = {71},
  year         = {2018},
}