HER2 amplification and HER2 low expression in endometrial carcinoma: prevalence across molecular, histological and clinicopathological risk groups.

Background: Emerging HER2-targeted therapies provide new treatment options for patients with HER2-expressing tumors. This study investigates the prevalence of HER2 amplification and HER2 low expression across a well-characterized cohort of endometrial carcinoma.

Methods: HER2 chromogenic in situ hybridization (CISH) was used to detect HER2 amplification in endometrial carcinoma samples. Chromogenic HER2 immunohistochemistry (IHC) was performed. HER2 low was defined as IHC 1 + /2+ and negative CISH.

Results: CISH confirmed HER2 amplification in 2% (n = 26) of the 1239 endometrial carcinoma samples including all the IHC 3+ cases (n = 13) and 20% of the 2+ cases (n = 55). Amplified cases presented various histotypes but consisted almost exclusively of p53 abnormal tumors. HER2 low 2+ category (n = 44) was heterogeneous with regard to molecular subgroup and histotype with 64.3% of the patients having high-risk disease. HER2 status did not independently predict disease-specific survival.

Conclusions: p53 abnormal molecular subgroup predicts HER2 amplification better than histotype. HER2 low cases present a wide range of histotypes and molecular subgroups including many patients with high-risk uterine cancer. Future trials of anti-HER2 therapies will clarify the clinical relevance of HER2 low status, treatment indications and guidelines for HER2 testing in endometrial carcinoma.