title: Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients.
abstract: p63 and cytokeratin (CK) 5/6 are markers of basal and squamous differentiation in several normal epithelia and human tumors and are also suggested to be markers of progenitor or stem cells in certain stratified epithelia. In endometrial carcinoma, there is very limited information about the expression pattern of p63 or CK5/6 and no prognostic information. The aim of our study was to examine whether the expression of these markers was associated with a certain tumor phenotype in terms of other biomarkers, clinicopathologic characteristics and patient prognosis. Immunohistochemical expression of p63 and CK5/6 was examined using tissue microarrays (TMAs) in a large population-based series of 276 endometrial carcinomas with long and complete follow-up. Selected cases of normal and hyperplastic endometrium were examined for comparison (n = 15). Absence of p63 expression (70%) was significantly associated with nonendometrioid carcinomas, high histologic grade (FIGO), higher mitotic count and tumor cell proliferation by Ki-67, microsatellite instability (MSI) and loss of hMSH6 expression. A tendency toward reduced patient survival was also seen (p = 0.098). Presence of CK5/6 expression was more frequent in endometrioid tumors with squamous differentiation, while loss of CK5/6 expression (54%) was significantly associated with high FIGO stage, reduced beta-catenin expression, MSI and reduced patient survival (p = 0.0001); the latter was also found within the endometrioid subgroup (p = 0.0004). Multivariate survival analysis revealed that loss of CK5/6 expression had an independent prognostic impact in addition to well-known prognostic variables. Expression of both markers was increased in simple hyperplasia compared with normal endometrium. In complex hyperplasia, p63 expression was also increased, whereas CK5/6 was positive in areas with squamous differentiation only. Thus, loss of p63 or CK5/6 was associated with features of aggressive tumors, and lack of CK5/6 was significantly associated with reduced survival in multivariate analysis.
authors.affiliation: Gade Institute, Section for Pathology, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stefansson
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
mesh_terms: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007633:Keratins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D007633:Keratins