HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL PROGNOSTIC FACTORS IN HIGH-GRADE NON-ENDOMETRIOID CARCINOMAS OF THE ENDOMETRIUM (HG-NECs). IS IT POSSIBLE TO IDENTIFY SUB-GROUPS AT INCREASED RISK?

Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years. In the present study potential histopathological and immunohistochemical prognostic markers are investigated Consecutive cases of high grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. Each surgical specimen has been routinely processed, the most representative block has been selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, {beta}-catenin, Bcl-2 and cyclin D1. For each immunomarker the percentage of positive tumor cells were evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). 33 cases were eligible: 19 resulted FIGO I-II, 14 resulted FIGO III-IV. 12 patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months). Women with recurrent disease demonstrated a significant higher bcl2% (35.84{+/-}30.96% vs 8.09{+/-}11.56% p=0.0032) while DOD patients had higher ki67% (75{+/-}13.09% vs 58.6{+/-}19.97% p=0.033) and bcl2% of border significance (34.37{+/-}34.99% vs 13{+/-}17.97% p=0.078). As expected FIGO III-IV had a worse DFS (HR=3.34; 95%CI:1.1-10.99; p=0.034) and OS (HR=5.19; 95%CI: 1.27-21.14 p= 0.0217). Bcl2-high patients (bcl2>10%) demonstrated a significant worse DFS (HR=9.11; 95%CI: 2.6-32.4; p=0.0006) and OS (HR=7.63; 95%CI:1.7-34; p=0.0084); also PR low patients (PR[≤]10%) had a significant worse DFS (HR=3.74; 95%CI:1.2-11.9; p=0,02). HG-NEC represent an heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis often at an advanced stage at presentation. Bcl2 and PR may represent promising markers to identify a sub-group of patients having an even worse prognosis requiring a careful and close follow-up.