• Vol. 34 No. 7, 421–425
  • 15 August 2005

p53 and bcl-2 Expression in Invasive and Pre-invasive Uterine Papillary Serous Carcinoma and Atrophic Endometrium



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Introduction: Uterine papillary serous carcinoma (UPSC), a high-grade tumour, is known to be associated in some cases with an identifiable intraepithelial neoplasia (IEN) component. Biomarker studies incorporating this latter component are not well documented. One aim of the present study was to compare levels of immunohistochemical (IHC) expression of p53 tumour suppressor gene and bcl-2 oncoprotein between UPSC and IEN, as well as normal endometrium to determine its biologic significance. The other major aim was to determine if these IHC results have any bearing on survival data in this tumour. Materials and Methods: An immunoreactivity score was assigned for examination of p53 and bcl-2 expression in a total of 21 cases of UPSC, 9 with an evaluable IEN component and 11 with associated non-neoplastic endometrium. Statistical analysis of IHC results was performed, in addition to correlation with survival data and disease stage. Results: p53 was identified in 16/21 cases of UPSC (76%) and 8/9 cases of IEN (89%), and no cases of normal endometrium. By contrast, bcl-2 was positive in all normal endometria with less expression in UPSC leaving 15/21 (71%) cases positive, and in IEN, leaving 5/9 (55%) of cases positive. Differences in immunoreactive scores for both p53 and bcl-2 between UPSC and benign glands, as well as between IEN and benign glands reached statistical significance with P values of 0.006 and 0.014 for p53, and 0.003 and 0.027 for bcl-2 respectively. There was no statistical significance between values for UPSC and IEN. Cox regression analysis found no statistically significant relationship between patient survival time in early and late stages of disease, and p53 and bcl-2 immunoscores. Conclusions: The lack of a significant difference between the bcl-2 and p53 values for both UPSC and IEN suggests that these molecular alterations occur at an early stage of tumour pathogenesis. A potential advantage of the use of immunohistochemical markers is their application to routinely processed surgical specimens. In this case, bcl-2 and p53 were applied in UPSC to determine any potential significance, but neither marker proved to be a useful predictor of survival time or disease stage.

Major differences at clinicopathologic and molecular genetic levels are known to exist between the commonest variety of endometrial carcinoma, endometrioid adenocarcinoma (EC) and uterine papillary serous carcinoma (UPSC). The p53 tumour suppressor gene is expressed in the majority of cases of UPSC, in contrast to the usual situation in EC. Expression of the bcl-2 oncoprotein, which acts as an anti-apoptotic factor to prolong cell survival, has been less well-characterised than p53 in endometrial malignancies, and shown to have wide variability of expression. For both markers, the invasive phase of carcinoma, as well as normal and hyperplastic endometrium, have been examined, but the early stages of neoplasia for UPSC have not been as extensively analysed. To determine if p53 and bcl-2 have any role or possible significant interaction in the early stages of pathogenesis of UPSC, immunohistochemical (IHC) evaluation of 9 cases of intraepithelial neoplasia (IEN) phase of tumour was performed, and compared with findings in 21 cases of invasive tumour and 11 cases of non-neoplastic endometrial glands. Statistical correlation with the clinical parameters of disease stage and survival time was also performed.

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