title: Biomarkers and microsatellite instability analysis of curettings can predict the behavior of FIGO stage I endometrial endometrioid adenocarcinoma.
abstract: The prognostic value of molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly due to the fact that different studies have used mixtures of histotypes, FIGO stages and different non-standardized non-automated methods. We have evaluated the prognostic value of classical prognostic factors, molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in a population-based cohort of FIGO stage I endometrial endometrioid adenocarcinomas. Curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients were reviewed. Clinical information, including follow-up, was obtained from the patients' charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections and molecular biomarkers using tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan-Meier method) and multivariate (Cox model) survival analysis was performed. With median follow-up of 66 months (1-209), 14 (6%) patients developed metastases. Age, microsatellite instability, molecular biomarkers (p16, p21, p27, p53 and survivin) and morphometric mean shortest nuclear axis had prognostic value. With multivariate analysis, combined survivin, p21 and microsatellite instability overshadowed all other variables. Patients in which any of these features had favorable values had an excellent prognosis, in contrast to those with either high survivin or low p21 (97 vs 78% survival, P<0.0001, hazard ratio=7.8). Combined high survivin and low p21 values and microsatellite instability high identified a small subgroup with an especially poor prognosis (survival rate 57%, P=0.01, hazard ratio=5.6). We conclude that low p21 and high survivin expression are poor prognosis indicators in FIGO stage I endometrial endometrioid adenocarcinoma, especially when high microsatellite instability occurs.
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Steinbakk
authors.forename: Anais
authors.initials: A
authors.lastname: Malpica
authors.forename: Aida
authors.initials: A
authors.lastname: Slewa
authors.forename: Ivar
authors.initials: I
authors.lastname: Skaland
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.forename: Kjell
authors.initials: K
authors.lastname: Løvslett
authors.forename: Bent
authors.initials: B
authors.lastname: Fiane
authors.forename: Arnold Jan
authors.initials: AJ
authors.lastname: Kruse
authors.forename: Weiwei
authors.initials: W
authors.lastname: Feng
authors.forename: Yu
authors.initials: Y
authors.lastname: Yinhua
authors.forename: Jan P
authors.initials: JP
authors.lastname: Baak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D004107:Dilatation and Curettage; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics; D053208:Kaplan-Meier Estimate; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D000077022:Survivin; D046888:Tissue Array Analysis
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin