title: p19(INK4d) mRNA and protein expression as new prognostic factors in ovarian cancer patients.
abstract: p19(INK4d) (CDKN2D) is a negative regulator of the cell cycle. Little is known of its role in cancer development and prognosis. We aimed to evaluate the clinical significance of p19(INK4d) expression in ovarian carcinomas with respect to the TP53 accumulation status, as well as the frequency of CDKN2D mutations. p19(INK4d) and TP53 expression was evaluated immunohistochemically in 445 ovarian carcinomas: 246 patients were treated with platinum-cyclophosphamide (PC/PAC), while 199 were treated with taxane-platinum agents (TP). CDKN2D gene expression (mRNA) was examined in 106 carcinomas, while CDKN2D mutations in 68 tumors. Uni- and multivariate statistical analyses (logistic regression and the Cox proportional hazards model) were performed for patient groups divided according to the chemotherapeutic regimen administered, and in subgroups with and without TP53 accumulation. High p19(INK4d) expression increased the risk of death, but only in patients with the TP53-negative carcinomas (HR 1.61, P = 0.049 for PC/PAC-treated patients, HR 2.00, P = 0.015 for TP-treated patients). This result was confirmed by the mRNA analysis (HR 4.24, P = 0.001 for TP-treated group). High p19(INK4d) protein expression associated with adverse clinicopathological factors. We found no alterations in the CDKN2D gene; the c.90C>G (p.R30R; rs1968445) polymorphism was detected in 10% of tumors. Our results suggest that p19(INK4d) expression is a poor prognostic factor in ovarian cancer patients. Analyses of tumor groups according to the TP53 accumulation status facilitate the identification of cancer biomarkers.
authors.affiliation: Department of Pathology; The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology; Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Felisiak-Golabek
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dansonka-Mieszkowska
authors.forename: Iwona K
authors.initials: IK
authors.lastname: Rzepecka
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szafron
authors.forename: Ewa
authors.initials: E
authors.lastname: Kwiatkowska
authors.forename: Bozena
authors.initials: B
authors.lastname: Konopka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Podgorska
authors.forename: Alina
authors.initials: A
authors.lastname: Rembiszewska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kupryjanczyk
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D050764:Cyclin-Dependent Kinase Inhibitor p19 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C493974:CDKN2D protein, human; D050764:Cyclin-Dependent Kinase Inhibitor p19; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: CDKN2D; TP53; chemotherapy; immunohistochemistry; ovarian cancer; p19INK4d; prognostic factor; real-time qPCR
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