Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

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Abstract

Background: HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. Methods: HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. Results: Eighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22–0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13–0.83), P <0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared. Conclusions: HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2. © 2016 The International Gastric Cancer Association and The Japanese Gastric Cancer Association
Original languageEnglish
Pages (from-to)428-437
Number of pages10
JournalGastric Cancer
Volume20
Issue number3
DOIs
Publication statusPublished - 2017

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Epirubicin
Adenocarcinoma
Drug Therapy
Immunohistochemistry
Biopsy
Stomach Neoplasms
Biomarkers
Selection Bias
Gene Amplification
Anthracyclines
Fluorescence In Situ Hybridization
Disease-Free Survival
Neoplasms
Breast Neoplasms
Survival
Proteins

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@article{37dafc34140b4633b152169dd3e21cd1,
title = "Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications",
abstract = "Background: HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. Methods: HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. Results: Eighteen of 101 patients (17.8 {\%}) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 {\%}). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 {\%} CI 0.22–0.99), P = 0.046] and overall survival [HR = 0.33 (95 {\%} CI 0.13–0.83), P <0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 {\%} of pairs, while this rate increased up to 27.2 {\%} when diagnostic biopsies and paired surgical samples were compared. Conclusions: HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2. {\circledC} 2016 The International Gastric Cancer Association and The Japanese Gastric Cancer Association",
author = "N Personeni and M Baretti and S Bozzarelli and P Spaggiari and L Rubino and MC Tronconi and {Fumagalli Romario}, U and R Rosati and L Giordano and M Roncalli and A Santoro and L Rimassa",
year = "2017",
doi = "10.1007/s10120-016-0625-1",
language = "English",
volume = "20",
pages = "428--437",
journal = "Gastric Cancer",
issn = "1436-3291",
publisher = "Springer Japan",
number = "3",

}

TY - JOUR

T1 - Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

AU - Personeni, N

AU - Baretti, M

AU - Bozzarelli, S

AU - Spaggiari, P

AU - Rubino, L

AU - Tronconi, MC

AU - Fumagalli Romario, U

AU - Rosati, R

AU - Giordano, L

AU - Roncalli, M

AU - Santoro, A

AU - Rimassa, L

PY - 2017

Y1 - 2017

N2 - Background: HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. Methods: HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. Results: Eighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22–0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13–0.83), P <0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared. Conclusions: HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2. © 2016 The International Gastric Cancer Association and The Japanese Gastric Cancer Association

AB - Background: HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. Methods: HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. Results: Eighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22–0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13–0.83), P <0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared. Conclusions: HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2. © 2016 The International Gastric Cancer Association and The Japanese Gastric Cancer Association

U2 - 10.1007/s10120-016-0625-1

DO - 10.1007/s10120-016-0625-1

M3 - Article

VL - 20

SP - 428

EP - 437

JO - Gastric Cancer

JF - Gastric Cancer

SN - 1436-3291

IS - 3

ER -