Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes.
- Abstract:
- PURPOSE: Advanced-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 DESIGN: Discovery 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). RESULTS: Infiltrative 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%). CONCLUSIONS: An 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.
- Authors:
- NS Meagher, KL Gorringe, M Wakefield, A Bolithon, CNI Pang, DS Chiu, MS Anglesio, K-A Mallitt, JA Doherty, HR Harris, JM Schildkraut, A Berchuck, KL Cushing-Haugen, K Chezar, A Chou, A Tan, J Alsop, E Barlow, MW Beckmann, J Boros, DDL Bowtell, AOCS Group, AH Brand, JD Brenton, I Campbell, D Cheasley, J Cohen, C Cybulski, E Elishaev, R Erber, R Farrell, A Fischer, Z Fu, B Gilks, AJ Gill, Australian Pancreatic Genome Initiative, C Gourley, M Grube, PR Harnett, A Hartmann, A Hettiaratchi, CK Høgdall, T Huzarski, A Jakubowska, M Jimenez-Linan, CJ Kennedy, B-G Kim, J-W Kim, J-H Kim, K Klett, JM Koziak, T Lai, A Laslavic, J Lester, Y Leung, N Li, W Liauw, BWX Lim, A Linder, J Lubiński, S Mahale, C Mateoiu, S McInerny, J Menkiszak, P Minoo, S Mittelstadt, D Morris, S Orsulic, S-Y Park, CL Pearce, JV Pearson, MC Pike, CM Quinn, GR Mohan, J Rao, MJ Riggan, M Ruebner, S Salfinger, CL Scott, M Shah, H Steed, CJR Stewart, D Subramanian, S Sung, K Tang, P Timpson, RL Ward, R Wiedenhoefer, H Thorne, kConFab Investigators, PA Cohen, P Crowe, PA Fasching, J Gronwald, NJ Hawkins, E Høgdall, DG Huntsman, PA James, BY Karlan, LE Kelemen, S Kommoss, GE Konecny, F Modugno, SK Park, A Staebler, K Sundfeldt, AH Wu, A Talhouk, PDP Pharoah, L Anderson, A DeFazio, M Köbel, ML Friedlander, SJ Ramus
- Journal:
- Clin Cancer Res
- Citation info:
- 28(24):5383-5395
- Publication date:
- 15th Dec 2022
- Full text
- DOI