Approaching heterogeneity of human epidermal growth factor receptor 2 in surgical specimens of gastric cancer

Sofia Asioli, Francesca Maletta, Ludovica Verdun Di Cantogno, Maria A. Satolli, Marina Schena, Carla Pecchioni, Cristina Botta, Luigi Chiusa, Luca Molinaro, Luca Conti, Giuseppe Viale, Giuseppe Ingravallo, Eugenio Maiorano, Anna Sapino

Research output: Contribution to journalArticlepeer-review

Abstract

Gastric cancer shows intratumoral heterogeneity for human epidermal growth factor receptor 2 expression. We evaluated whether the number of tissue blocks analyzed or the antibodies used may influence the immunohistochemical results in gastrectomy specimens. Clinicopathologic data from 148 patients receiving gastric surgery for cancer were collected. One tissue block for each of 88 primary tumors and 60 paired primary tumors and metastases was examined for human epidermal growth factor receptor 2 status by immunohistochemistry using 3 different antibodies (HercepTest, CB11, and 4B5) and by fluorescent in situ hybridization. Two additional tissue blocks of the primary tumor were tested by immunohistochemistry if the results were negative on the first tissue block. The concordance among the 3 antibodies was 94.5% (testing 1 tissue block). Two cases showed a clinically significant discrepancy between primary tumor (score 0) and lymph nodes metastases (score 3+). Additional block analysis increased both the sensitivity (from 63% to 83%) and the accuracy (from 91% to 94%) of immunohistochemistry as compared with fluorescent in situ hybridization. The multiblock approach could potentially identify a greater number of human epidermal growth factor receptor 2-positive gastric cancers, particularly those with higher levels of intratumor heterogeneity. In turn, human epidermal growth factor receptor 2 positivity correlated with a worse prognosis (P =.011) and was an independent variable in multivariate analysis (hazard ratio, 1.57). In conclusion, testing more than 1 tissue block of cancer from specimens of gastric resection provides a more reliable human epidermal growth factor receptor 2 assessment regardless of the antibody used.

Original languageEnglish
Pages (from-to)2070-2079
Number of pages10
JournalHuman Pathology
Volume43
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Gastric cancer
  • HER2
  • Immunohistochemistry
  • Surgical specimen

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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