Using gene expression in patients with endometrial intraepithelial neoplasia to assess the risk of cancer

Patients diagnosed with an endometrial cancer precursor lesion on biopsy may be found to have endometrial cancer at the time of subsequent surgery. The current study seeks to identify patients with endometrial intraepithelial neoplasia (EIN) on biopsy that may be harboring an occult carcinoma. Immunohistochemical stains for gene loss of expression (LOE) for 6 genes, PTEN, ARID1A, MSH6, MSH2, MLH1, and PMS2, were performed on 113 biopsy specimens with EIN. For the 95 patients with follow-up histology, 40 patients had cancer, 41 had EIN, and 14 had normal endometrium. PTEN LOE was found frequently in both EIN and endometrial cancer, and therefore had low positive predictive value. All specimens with ARID1A, MSH6, MSH2, MLH1, or PMS2 LOE on biopsy were subsequently found to have cancer. LOE of any gene was associated with modest sensitivity (0.78) in identifying patients with endometrial cancer who had EIN on biopsy. Further investigation is warranted to determine if gene LOE is a useful clinical tool when evaluating patients with EIN on biopsy.