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.