Proliferating cell nuclear antigen in endometrial carcinoma: pretreatment identification of high-risk patients

The aim of our study was to retrospectively examine the proliferating cell nuclear antigen (PCNA) immunoreactivity of tumor cells in curettage specimens containing endometrioid adenocarcinoma and obtained immediately before definitive surgical staging. This PCNA index was compared with the one subsequently derived from surgical specimens and assessed as a function of histologic grade, depth of myometrial invasion, neoplastic nodal involvement, cervical spread, and progression-free survival in order to determine a new prognostic parameter valuable at the time of diagnosis.

A population of 79 patients with locally advanced (stage I and II) endometrioid carcinoma, who underwent both the preliminary diagnostic curettage and the subsequent definitive surgical management, selected from January 1986 to June 1993 at the Department of Gynecology and Obstetrics, Ancona University, was retrospectively recruited from our series of 99 endometrial carcinomas. The archival paraffin blocks from the curettage and uterine specimens were identified and assessed for histologic reexamination and PCNA immunostaining [PC10 monoclonal antibody (Dako, Denmark)].

After a median follow-up of 47 months, recurrences were detected in 7 cases, and the Kaplan-Meier disease-free survival curve estimated for the entire study group was 91%. The median PCNA index of the curettage specimens presented a good overlap with the PCNA immunostaining in corresponding uterine samples with a correlation coefficient of 0.4 (P=0.02). A PCNA index >/=30% in curettage specimen was predictive of deep myometrial invasion; of 35 patients with PCNA index > or = 30%, 29 (83%) had myometrial invasion > or = 50%. No significant relationship was observed with neoplastic cervical spread, and histologic differentiation. By Cox hazard analysis, the PCNA index evaluated on curettage specimens was significantly related to disease-free survival, with significant disease-free survival advantages for patients with PCNA <30% (P<0.001).

Our findings suggest that the PCNA immunostaining has proved to be considerably promising for the risk assessment in locally advanced endometrial carcinoma. The PCNA index is an objective and reproducible parameter accruably valuable also before starting the treatment; in presence of a high PCNA index, the patients should be referred to gynecologic oncologists for appropriate management.