In this report, the authors examined the characteristic features of morphology and molecular biology of Ki-67, p53, Bcl-2, and cyclooxygenase-2 (Cox-2) immunocytochemistry in low-grade endometrioid endometrial carcinoma (LG-ENEC) and disordered proliferative (DP)/benign hyperplastic (BH) endometrium. We carried out a prospective study by collecting endometrial imprints from freshly resected uteri over a 20-month period and finally 104 patients were evaluated with endometrial cytology. We focused on LG-ENECs, as well as on BH endometrium and its precursor lesion, DP endometrium, firstly because of the overlapping cytomorphology of these pathologic entities and secondly because of the lack of agreement in the differential diagnosis of atypical hyperplasia from complex hyperplasia and well-differentiated endometrial carcinoma, even in curettage specimens. Ki-67 expression of LG-ENEC showed predominance in comparison with DP/BH endometrium. Furthermore, high levels of Bcl-2 (>50%) were expressed only in DP/BH endometrium. DP/BH endometrium was negative for p53 marker, except from two cases of BH endometrium. Cox-2 expression ≥50% was found only in LG-ENECs. Using Ki-67, Bcl-2, p53, and Cox-2 markers, we managed to distinguish fully DP/BH endometrium from LG-ENEC. Higher Ki-67%/Bcl-2% rate and also higher Cox-2 expression were found in LG-ENEC cases with FIGO stage ≥ IC, than in cases with FIGO stage < IC. The immunocytochemical findings from a combination of Ki-67, p53, Bcl-2, and Cox-2, may differentiate LG-ENEC from DP/BH endometrium with overlapping cytomorphology. Immunocytochemistry appeared to be useful also for the correlation between LG-ENEC and FIGO stage.

The results of the present study demonstrated that evaluation of certain cytological features along with specific immunocytochemical findings could improve the accuracy of endometrial cytodiagnosis but our findings need to be tested in a routine clinical situation, using pre-operative cytological samples, to ascertain whether the diagnostic criteria are reproducible.

The different range of the nuclear area major axis among cycling endometrial epithelial and adenocarcinoma cells may correlate with their specific identity and biological behaviour. The different values of the cycling nuclear area major dimension may also be connected with the biological behaviour of the three examined groups. Moreover, the endometrial epithelial cells may follow a Ki-67 increase pathway, instead of the relatively stable pathway which the rapidly proliferating adenocarcinoma cells may use. Finally, the studied cell categories may exhibit different biology, because their stem cells may reside in different states of stemness.