The aim of this study was to determine the joint effect of single nucleotide polymorphisms (SNPs) of MDM2, TP53, and CDKN2A (P14ARF) genes on the onset and course of endometrial cancer (EC) in postmenopausal women.
For 276 cases, we obtained tissue blocks of endometrial cancer to review the diagnosis, and used immunohistochemistry to examine hormone-receptor status and overexpression of p53.
Immunohistochemical assessment of p53 overexpression in the nucleus and cytoplasm could provide useful prognostic information for the management of patients with endometrial cancer.
We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours.
Co-occurrence of some MDM2 SNP309 and TP53 codon 72 polymorphisms seems to influence EC risk, involving grading and staging of this neoplasm at the same time.
The association of the endometrial cancer cases with family history of breast cancer and the three TP53 polymorphisms suggests that this constellation of malignancies may represent a low-risk familial cancer grouping.
Adenovirus-mediated expression of p53 or p21 in a papillary serous endometrial carcinoma cell line (SPEC-2) results in both growth inhibition and apoptotic cell death: potential application of gene therapy to endometrial cancer.
The homozygous variants of wild p53 codon 72 and mutant MDM2 promoter 309 may cooperatively increase the risk of endometrial cancer in a Japanese population.
Estrogen receptor (ER), progesterone receptor (PR), and Ki-67 and P53 receptor levels in endometrial curettage material were investigated for their ability to predict lymph node (LN) involvement in patients with endometrioid-type endometrial cancer (EEC).
These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.
Our results suggest that homozygous arginine at codon 72 of p53 may represent a risk factor for developing ovarian malignancies and may affect the differentiation of endometrial cancer.
Consequently, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial cancer, although a still larger sample of patient material would be required to assess this issue definitively.
Following these results, immunohistochemistry with the PAb monoclonal antibody may be safely used as a screening tool for the detection of mutated p53 in clinical samples of mammary and endometrial cancer, whereas it should be complemented with DNA analysis in cervix carcinoma.
Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial cancer.