학술논문
Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.
Document Type
article
Author
Meagher, Nicola S; Gorringe, Kylie L; Wakefield, Matthew; Bolithon, Adelyn; Pang, Chi Nam Ignatius; Chiu, Derek S; Anglesio, Michael S; Mallitt, Kylie-Ann; Doherty, Jennifer A; Harris, Holly R; Schildkraut, Joellen M; Berchuck, Andrew; Cushing-Haugen, Kara L; Chezar, Ksenia; Chou, Angela; Tan, Adeline; Alsop, Jennifer; Barlow, Ellen; Beckmann, Matthias W; Boros, Jessica; Bowtell, David DL; Group, for the AOCS; Brand, Alison H; Brenton, James D; Campbell, Ian; Cheasley, Dane; Cohen, Joshua; Cybulski, Cezary; Elishaev, Esther; Erber, Ramona; Farrell, Rhonda; Fischer, Anna; Fu, Zhuxuan; Gilks, Blake; Gill, Anthony J; Initiative, for the Australian Pancreatic Genome; Gourley, Charlie; Grube, Marcel; Harnett, Paul R; Hartmann, Arndt; Hettiaratchi, Anusha; Høgdall, Claus K; Huzarski, Tomasz; Jakubowska, Anna; Jimenez-Linan, Mercedes; Kennedy, Catherine J; Kim, Byoung-Gie; Kim, Jae-Weon; Kim, Jae-Hoon; Klett, Kayla; Koziak, Jennifer M; Lai, Tiffany; Laslavic, Angela; Lester, Jenny; Leung, Yee; Li, Na; Liauw, Winston; Lim, Belle WX; Linder, Anna; Lubiński, Jan; Mahale, Sakshi; Mateoiu, Constantina; McInerny, Simone; Menkiszak, Janusz; Minoo, Parham; Mittelstadt, Suzana; Morris, David; Orsulic, Sandra; Park, Sang-Yoon; Pearce, Celeste Leigh; Pearson, John V; Pike, Malcolm C; Quinn, Carmel M; Mohan, Ganendra Raj; Rao, Jianyu; Riggan, Marjorie J; Ruebner, Matthias; Salfinger, Stuart; Scott, Clare L; Shah, Mitul; Steed, Helen; Stewart, Colin JR; Subramanian, Deepak; Sung, Soseul; Tang, Katrina; Timpson, Paul; Ward, Robyn L; Wiedenhoefer, Rebekka; Thorne, Heather; Investigators, for the kConFab; Cohen, Paul A; Crowe, Philip; Fasching, Peter A; Gronwald, Jacek; Hawkins, Nicholas J; Høgdall, Estrid; Huntsman, David G; James, Paul A; Karlan, Beth Y; Kelemen, Linda E
Source
Clinical Cancer Research. 28(24)
Subject
Language
Abstract
PurposeAdvanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental designDiscovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).ResultsInfiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).ConclusionsAn infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.