OBSERVATIONS ON TUMOR AND METASTATIC SUPPRESSOR GENE STATUS IN ENDOMETRIAL CARCINOMA WITH PARTICULAR EMPHASIS ON P53

Background. Genetic changes in the development of endometrial carcinom a have not been characterized, and little is known of tumor or metasta tic suppressor gene status in these malignancies. The current study on endometrioid carcinoma was undertaken to examine the status of two tu mor suppressor genes that frequently have been found to be altered in human malignancies (the p53 gene and the retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic suppressor gene, nm 23-H1. Methods. The status of the p53 gene was studied by immunohistoc hemistry of formalin-fixed paraffin-embedded biopsy samples from 72 pa tients with atypical endometrial hyperplasia or endometrioid carcinoma who underwent hysterectomy immediately after biopsy and from 5 patien ts with benign endometria. A search for loss of heterozygosity (LOH) o f the nm23 gene after DNA extraction from frozen tissues and hybridiza tion with nm23-H1 cDNA specific probe was made in 10 endometrial carci nomas. Rb gene status was evaluated by image analysis quantification o f immunoreactive retinoblastoma protein in frozen sections of 10 carci nomas and 2 benign endometria. Results. p53 expression was low in all benign endometria, but high expression was found in 2 (15%) of 13 atyp ical hyperplasias and in 23 (39%) of 59 carcinomas. High levels of p53 expression in endometrioid carcinoma correlated with the spread of di sease outside of the uterus and by logistic regression, the presence o f squamous differentiation, nuclear grade, and high p53 expression in the biopsy all independently correlated with spread of disease outside of the uterus. Although 7 of the 10 carcinomas studied were informati ve, LOH for the nm23 gene was not seen in any, including a site of met astasis. Rb protein expression in endometrial carcinoma was similar to expression in benign endometria.Conclusions. Although this study foun d no evidence of nm23-H1 gene alteration or alterations in Rb protein levels in endometrial carcinoma, high expression of p53 protein was sp oradically identified in biopsy specimens of atypical hyperplasia and frequently found in endometrioid carcinomas. Determination of p53 expr ession in combination with the presence or absence of squamous differe ntiation and nuclear grade in biopsy material may help predict spread of endometrioid carcinoma outside the uterus and facilitate therapeuti c planning before hysterectomy.