| Title: |
Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study |
| Authors: |
Rambau, PF; Vierkant, RA; Intermaggio, MP; Kelemen, LE; Goodman, MT; Herpel, E; Pharoah, PD; Kommoss, S; Jimenez-Linan, M; Karlan, BY; Gentry-Maharaj, A; Menon, U; Polo, SH; Candido Dos Reis, FJ; Doherty, JA; Gayther, SA; Sharma, R; Larson, MC; Harnett, PR; Hatfield, E; de Andrade, JM; Nelson, GS; Steed, H; Schildkraut, JM; Carney, ME; Høgdall, E; Whittemore, AS; Widschwendter, M; Kennedy, CJ; Wang, F; Wang, Q; Wang, C; Armasu, SM; Daley, F; Coulson, P; Jones, ME; Anglesio, MS; Chow, C; de Fazio, A; García-Closas, M; Brucker, SY; Cybulski, C; Harris, HR; Hartkopf, AD; Huzarski, T; Jensen, A; Lubiński, J; Oszurek, O; Benitez, J; Mina, F; Staebler, A; Taran, FA; Pasternak, J; Talhouk, A; Rossing, MA; Hendley, J; Edwards, RP; Fereday, S; Modugno, F; Ness, RB; Sieh, W; El-Bahrawy, MA; Winham, SJ; Lester, J; Kjaer, SK; Gronwald, J; Sinn, P; Fasching, PA; Chang-Claude, J; Moysich, KB; Bowtell, DD; Hernandez, BY; Luk, H; Behrens, S; Shah, M; Jung, A; Ghatage, P; Alsop, J; Alsop, K; García-Donas, J; Thompson, PJ; Swerdlow, AJ; Karpinskyj, C; Cazorla-Jiménez, A; García, MJ; Deen, S; Wilkens, LR; Palacios, J; Berchuck, A; Koziak, JM; Brenton, JD; Cook, LS; Goode, EL; Huntsman, DG; Ramus, SJ ; https://orcid.org/0000-0003-0005-7798; Köbel, M |
| Source: |
urn:ISSN:2056-4538; Journal of Pathology Clinical Research, 4, 4, 250-261 |
| Publisher Information: |
Wiley 2018-10-01 |
| Document Type: |
Electronic Resource |
| Abstract: |
We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition. |
| Index Terms: |
32 Biomedical and Clinical Sciences; 3211 Oncology and Carcinogenesis; Cancer; Human Genome; Ovarian Cancer; Genetics; Women's Health; Rare Diseases; Orphan Drug; Precision Medicine; 2.1 Biological and endogenous factors; Adenocarcinoma, Mucinous; Adult; Aged; Cyclin-Dependent Kinase Inhibitor p16; Cystadenocarcinoma, Serous; Female; Humans; Immunohistochemistry; Middle Aged; Ovarian Neoplasms; Ovary; Prognosis; Survival Rate; RT-QPCR; immunocytochemistry; AOCS Group; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 3211 Oncology and Carcinogenesis; anzsrc-for: 111402 Obstetrics and Gynaecology; anzsrc-for: 111209 Solid Tumours; anzsrc-for: 3202 Clinical sciences; journal article; http://purl.org/coar/resource_type/c_6501 |
| URL: |
http://hdl.handle.net/1959.4/unsworks_56002; https://doi.org/10.1002/cjp2.109 |
| Availability: |
Open access content. Open access content; open access; https://purl.org/coar/access_right/c_abf2; CC BY; https://creativecommons.org/licenses/by/4.0 |
| Other Numbers: |
LJ1 oai:unsworks.library.unsw.edu.au:1959.4/unsworks_56002; 1089650321 |
| Contributing Source: |
UNIV OF NEW S WALES; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1089650321 |
| Database: |
OAIster |