We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3'UTR mutation associated with increased expression in endometrial cancer.
We previously showed that mitogenic 17-β-estradiol (E2) induces degradation of p27 by the E3 ligase Skp1-Cullin1-F-Box- S phase kinase-associated protein2/cyclin dependent kinase regulatory subunit 1 in primary endometrial epithelial cells and endometrial carcinoma (ECA) cell lines, suggesting a pathogenic mechanism for type I ECA, an E2-induced cancer.
Cyclin E and p53 expression was studied by immunohistochemistry in eight atypical endometrial hyperplasias (AEHs), 51 endometrioid endometrial carcinomas (EECs), and 22 non-endometrioid endometrial carcinomas (NEECs).
Cyclin E gene amplification was observed in 15 different tumour types and subtypes, ie rhabdomyosarcoma, urinary bladder cancer (three subtypes), ovarian cancer (two subtypes), malignant fibrous histiocytoma, adenocarcinoma of the small intestine, medullary breast cancer, gall bladder adenocarcinoma, phaeochromocytoma, gastric adenocarcinoma, squamous cell carcinoma of the uterine cervix, colonic adenocarcinoma, and endometrial carcinoma.
Sixty-three percent of endometrial carcinomas showed strong positivity for both hMSH2 and PCNA expression, and 7.4% had an intensity of hMSH2 protein expression similar to that found in normal proliferative endometrial glandular cells.
The aim of the current study was to perform methodologic, descriptive, comparative, and prognostic studies of Ki-67, proliferating cell nuclear antigen (PCNA), and flow cytometric S-phase fraction (SPF) in endometrial carcinoma.