Department of Oncology, Institut Mutualiste Montsouris, Paris, France
Sarah Watson , Pierre Validire , Pascale Cervera , Nabila Zorkani , Frederic Lemay , Thierry Perniceni , Francois Paye , Christophe Tournigand , Christophe Louvet
Background: HER2 is overexpressed in 10 to 20% of gastro-esophageal adenocarcinoma (GE-ADK), and is a target for trastuzumab in metastatic patients. We conducted a study to compare HER2 expression between diagnostic biopsies (DB) and surgical specimens (SS) of GE-ADK, and to determine the influence of non-trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression. Methods: Pathological specimens from biopsies of 228 patients operated on with a curative aim in two French hospitals between 2004 and 2011 were collected. Two cohorts treated (n=141) or not (n=87) with a NAC were constituted. Two blind independent pathological HER2 analyses on DB and on SS were performed using IHC and CISH. HER-2 overexpression (HER2 +) was defined by a score 3+ in IHC, or 2+ with a positive CISH test, and according to the specific HER2 scoring guidelines for GE-ADK. Results: Paired HER2 status could be determined for 218 out of the 228 patients (95.6%). HER2 + rates were 13.3% on DB (29/218) and 14.7% on SS (32/218). HER2 + tumors were mainly cardial or esophageal adenocarcinomas, with a well-differentiated, intestinal histological type. HER2 status differed between DB and SS in 13 patients (6%). When DB analyses were added to SS analyses, 5 additional patients were HER2 +, the relative increase in HER2 + cases being 13.5% (17.1% for patients with NAC versus 7.1% for patients without NAC, p=0.4, NS). Differences between DB and SS HER2 expression could be explained by the intratumoral heterogeneity and also by a possible HER2 expression decrease in SS after NAC. Conclusions: The determination of HER2 status on DB provides results that complete those obtained with SS. Combining the analysis of DB and of SS enables to optimize the selection of trastuzumab-eligible patients in case of metastatic relapse, especially in patients previously treated with NAC.
Diagnostic Biopsy Surgical Specimen |
No NAC (N = 83) | NAC (N = 135) | Total | |||
---|---|---|---|---|---|---|
HER2 + | HER2 - | HER2 + | HER2- | |||
No NAC (N = 83) |
HER2 + | 9 | 4 | 13 (15.7%) | ||
HER2 - | 1 | 69 | 70 | |||
NAC (N = 135) |
HER2 + | 15 | 4 | 19 (14.1%) | ||
HER2 - | 4 | 112 | 116 | |||
Total | 10 (12.0%) | 73 | 19 (14.1%) | 116 | 218 |
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