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Overexpression and Mutation of p53 in Endometrial Carcinoma¹

Departments of Obstetrics and Gynecology/Gynecologic Oncology [M. F. K., A. B., J. T. S., D. L. C-P.], Surgery [A.M. D., J. D. I., J. R. M.], Pathology [P. A. H.], Biostatistics [R. K. D.], Medicine and Microbiology/Immunology [R. C. B.], and the Duke University Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina 27710

Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P < 0.001), and also was associated with nonendometrioid histology (P = 0.008), positive peritoneal cytology (P = 0.01), extrauterine metastases (P = 0.003), and negative progesterone receptor status (P = 0.04). To confirm the relationship between p53 overexpression and mutation, p53 mRNA from 8 cancers was reverse transcribed and amplified using the polymerase chain reaction. DNA sequencing revealed point mutations in each of the 5 cancers that overexpressed p53, whereas the wild-type sequence was found in 3 cancers that did not overexpress the protein. Each of the 5 mutations resulted in an amino acid substitution in a highly conserved region of the p53 gene where mutations have been found in other cancers. Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.

¹ Supported in part by the Seelinger Award in Cancer Research, Duke Comprehensive Cancer Center, Duke University Medical Canter.

² To whom requests for reprints should be addressed, at Box 3079, Duke University Medical Center, Durham, NC 27710.

Received 8/26/91. Accepted 12/30/91.

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