p53 Protein Overexpression: A Strong Prognostic Factor in Uterine Papillary Serous Carcinoma

Abstract & Commentary

Synopsis: Patients with uterine papillary serous carcinoma whose tumors overexpress p53 have a worse prognosis than those whose tumors do not.

Source: Bancher-Todesca D, et al. Gynecol Oncol 1998;71:59-63.

In a study from australia, bancher-todesca and colleagues investigated 23 cases of uterine papillary serous carcinoma (UPSC). P53 expression was studied in archival paraffin-embedded tissue by immunohistochemistry. Eleven tumors (47.8%) revealed p53 overexpression whereas 12 tumors (52.2%) were p53 negative. One of eight stage I/II (12.5%) and 10/15 stage III/IV (66.6%) tumors revealed p53 immunostaining (P = 0.027). The median overall survival was 43.3 months. Patients with advanced-stage (III and IV) disease had a five-year overall survival probability of 24% compared to 100% in those in stages I and II (P = 0.018). Myometrial invasion, lymphatic space invasion, and lymph node involvement did not correlate with the five-year overall survival of these patients. Patients whose tumors overexpressed p53 had a significantly shorter survival than those whose tumors did not (P = 0.033). This study confirms the influence of p53 overexpression on survival in UPSC patients.

Comment by David M. Gershenson, MD

Mutation of the tumor suppressor gene p53 is a common finding in gynecologic neoplasms. In this study, Bancer-Todesca et al found that almost 50% of UPSC had p53 overexpression, an indirect measure of p53 mutation. Another study found that 71.4% of 21 UPSC overexpressed p53.1 This was in comparison with only 28.6% of endometrioid uterine cancers. In this same study, there was a trend toward p53 overexpression being more common in late-stage than early-stage UPSC—90% vs. 50%—but the difference was not statistically significant. In the present study, the marked difference in the incidence of p53 overexpression between late- and early-stage disease—66.6% vs. 12.5%—did achieve statistical significance. The present study represents yet another report that characterizes a specific tumor type with respect to a common molecular biomarker. As this information accumulates and is confirmed, in some instances it will allow clinicians to predict outcome of individual patients and also, eventually, plan therapy based on the findings. In addition, the specific molecular defect itself may prompt treatment with a specific agent. The current testing of p53 gene therapy is but one example of such an approach. Importantly, as Bancher-Todesca et al point out, we need a study with a much larger number of patients with whom to perform a multivariate analysis so that we can determine the independent influence of p53 overexpression in UPSC.

Reference

1. Zheng W, et al. Gynecol Oncol 1996;61:167-174.