Trastuzumab-Eligible Patients in Eso-Gastric Adenocarcinoma
Trastuzumab-Eligible Patients in Eso-Gastric Adenocarcinoma
All patients presenting the following inclusion criteria were included
We excluded patients for whom diagnostic pre-treatment biopsies could not be collected, or for whom the pathological material from the DBs was depleted or non-interpretable.
Two cohorts were designed; the NAC cohort for patients who received a 5-FU and platinum salt-based NAC before surgery; and the No-NAC cohort for patients who didn't receive NAC.
All the living patients were informed of the goal of the study by letter and asked whether they agreed to participate. Clinical and pathological data were centralized in a controlled and access-limited database. The protocol was approved by institutional review board according to the national requirements.
Pathological centers in which diagnostic paraffin-embedded biopsies had been analyzed and stored were asked for tumoral material from each patient. Paraffin-embedded blocks from surgical specimens were stored since the date of surgery in both investigating centers. Paired samples (containing the DBs and one block from the surgical specimen) were anonymised and identifiable by a histology and study number.
IHC was carried out on all available paired samples. HER2 expression was detected using the anti HER2/neu (clone 4B5) antibody on an automated immunostainer (Benchmark XT Ventana) according to manufacturer's instructions. HER2 status was determined using the validated scoring guidelines for GE-ADK.
All tumor pairs that showed a score 2+ on the biopsy and/or the surgical specimen were tested for HER2 amplification in dual CISH (BenchMark XT, Ventana HER2 dual-color ISH assay). Amplification of HER2 was defined as a ratio HER2/CEP17 ≥ 2, as recommended. All IHC and CISH tests were analyzed with two independent blind readings by two specialists in pathology. In case of discordance between both analyses, a third reading was carried out conjointly to reach a consensus. HER2-overexpressing (HER2+) tumors were defined as 3+ in IHC or 2+ in IHC with amplification in CISH.
NAC histological response was established on surgical specimens according to the usual guidelines for GE-ADK.
Patients and Methods
Study Population, Therapeutic Strategies and Design
All patients presenting the following inclusion criteria were included
Histological proof of gastric or oeso-gastric (low oesophagus and cardia) adenocarcinoma,
Surgery with a curative aim carried out between 1 January 2004 and 31 December 2011 in Institut Mutualiste Montsouris or in Hôpital Saint-Antoine.
We excluded patients for whom diagnostic pre-treatment biopsies could not be collected, or for whom the pathological material from the DBs was depleted or non-interpretable.
Two cohorts were designed; the NAC cohort for patients who received a 5-FU and platinum salt-based NAC before surgery; and the No-NAC cohort for patients who didn't receive NAC.
All the living patients were informed of the goal of the study by letter and asked whether they agreed to participate. Clinical and pathological data were centralized in a controlled and access-limited database. The protocol was approved by institutional review board according to the national requirements.
Constitution of Pathological Collections
Pathological centers in which diagnostic paraffin-embedded biopsies had been analyzed and stored were asked for tumoral material from each patient. Paraffin-embedded blocks from surgical specimens were stored since the date of surgery in both investigating centers. Paired samples (containing the DBs and one block from the surgical specimen) were anonymised and identifiable by a histology and study number.
Pathological Analyses
IHC was carried out on all available paired samples. HER2 expression was detected using the anti HER2/neu (clone 4B5) antibody on an automated immunostainer (Benchmark XT Ventana) according to manufacturer's instructions. HER2 status was determined using the validated scoring guidelines for GE-ADK.
All tumor pairs that showed a score 2+ on the biopsy and/or the surgical specimen were tested for HER2 amplification in dual CISH (BenchMark XT, Ventana HER2 dual-color ISH assay). Amplification of HER2 was defined as a ratio HER2/CEP17 ≥ 2, as recommended. All IHC and CISH tests were analyzed with two independent blind readings by two specialists in pathology. In case of discordance between both analyses, a third reading was carried out conjointly to reach a consensus. HER2-overexpressing (HER2+) tumors were defined as 3+ in IHC or 2+ in IHC with amplification in CISH.
NAC histological response was established on surgical specimens according to the usual guidelines for GE-ADK.
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