title: Down-regulation of bcl-2 expression is closely related to squamous differentiation and progesterone therapy in endometrial carcinomas.
abstract: To clarify whether changes in bcl-2 protein (bcl-2) expression are directly linked to differentiation, an immunohistochemical investigation was carried out on areas of squamous differentiation within 38 endometrial carcinomas (25 grade 1 and 13 grade 2 cases) as well as eight grade 1 carcinomas after progesterone therapy. Such areas of altered differentiation were subdivided into foci of squamous metaplasia (Sq-M) and morules. Expression of oestrogen and progesterone receptors (ER and PR) and cell proliferation were also examined. Immunoreactivity scores for bcl-2 in Sq-M foci were significantly lower than in the surrounding tumour regions, in line with reduced staining for ER and PR and Ki-67 labelling indices (LIs), while morule values were intermediate. After progesterone therapy, a marked decrease in bcl-2 immunoreactivity was found in the response group, along with low Ki-67 LIs and tumour cell maturation. These results indicate that in endometrial carcinoma, down-regulation of bcl-2 expression may be closely linked with squamous differentiation, in line with changes in ER and PR expression, as well as in cell proliferation. In addition, bcl-2 expression appears to be down-regulated by progesterone therapy through tumour cell maturation, indicating that bcl-2 may be a clinically useful marker of hormone therapy effects.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saegusa
authors.forename: I
authors.initials: I
authors.lastname: Okayasu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D011374:Progesterone / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone