Abstract
The important role of the p53 gene in tumour progression and cellular response to DNA damage has prompted investigation of the clinical significance of alterations to this gene. We examined both p53 overexpression and mutation of the gene in endometrial carcinoma in order to evaluate the prognostic significance of these changes. Of 122 endometrial carcinomas, 33 (27%) showed overexpression of p53 in the nucleus and 66 (54%) in the cytoplasm. Mutation in the p53 gene was found in 16 (13%) cases but showed no significant association with patient survival. Nuclear p53 overexpression was associated with poor survival (48% vs 80% alive in negative tumours 5 years post operatively, P < 0.001). In contrast, cytoplasmic p53 overexpression was associated with better survival (85% vs 55%, P < 0.001). When patients were separated into prognostic subgroups according to established clinical markers, these associations remained significant within most subgroups examined. In multivariate analysis adjusted for surgical stage, histological grade and type and vascular invasion, both nuclear p53 overexpression [hazard ratio 4.9 (95% CI 1.3-17.6). P = 0.016] and cytoplasmic overexpression [0.25 (0.06-0.98), P = 0.047] were independent prognostic factors. Immunohistochemical assessment of p53 overexpression in the nucleus and cytoplasm could provide useful prognostic information for the management of patients with endometrial cancer.
Highlights
In this study we examined the prognostic significance of both p53 overexpression and gene mutation in 122 endometrial carcinomas from patients with a long follow
We report the novel observation of improved survival in cases with cytoplasmic accumulation of p53 protein
We found the detection of mutations using both systems to be identical for 41 different p53 mutations (R Soong, in preparation)
Summary
Paraffin-embedded tissue blocks from 122 patients operated for primary endometrial carcinoma over the period 1979-87 were selected from the archives of King Edward Memorial Hospital for Women. Haematoxylin-and eosinstained sections were examined by a pathologist (KEW) to enable selection of blocks with maximal tumour content. Hormonal therapy or irradiation was conducted before surgical excision of tumours. The histological subtypes were endometrioid (94 cases), serous papillary (14), clear cell (four), adenosquamous (three) and mucinous (seven). Other clinicopathological parameters such as peritoneal cytology, steroid receptor levels, myometrial invasion and surgical management were recorded in each patient report. At the end of the study period, 35 (29%) patients had died as a result of spread of their primary tumour
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