title: Utility of Ki-67, p53, Bcl-2, and Cox-2 biomarkers for low-grade endometrial cancer and disordered proliferative/benign hyperplastic endometrium by imprint cytology.
abstract: 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.
authors.affiliation: Department of Cytopathology, Anti-cancer Oncological Hospital St. Savvas, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Apostolou
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Apostolou
authors.forename: Maria
authors.initials: M
authors.lastname: Biteli
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Paulina
authors.initials: P
authors.lastname: Athanassiadou
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003937:Diagnosis, Differential; D004714:Endometrial Hyperplasia / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000737:chemistry*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis* / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2
keywords: benign hyperplastic endometrium; disordered proliferative endometrium; immunocytochemistry; imprint cytology; low-grade endometrioid adenocarcinoma