Gene-expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes

N. S. Meagher, K. L. Gorringe, M. Wakefield, A. Bolithon, C. N. I. Pang, D. S. Chiu, M. S. Anglesio, K. -A. Mallitt, J. A. Doherty, H. R. Harris, J. M. Schildkraut, A. Berchuck, K. L. Cushing-Haugen, K. Chezar, A. Chou, A. Tan, J. Alsop, E. Barlow, M. W. Beckmann, J. BorosD. D. L. Bowtell, A. H. Brand, J. D. Brenton, I. Campbell, D. Cheasley, J. Cohen, C. Cybulski, E. Elishaev, R. Erber, R. Farrell, A. Fischer, Z. Fu, B. Gilks, A. J. Gill, C. Gourley, M. Grube, P. R. Harnett, A. Hartmann, A. Hettiaratchi, C. K. Høgdall, T. Huzarski, A. Jakubowska, M. Jimenez-Linan, C. J. Kennedy, B. -G. Kim, J. -W. Kim, J. -H. Kim, K. Klett, J. M. Koziak, T. Lai, A. Laslavic, J. Lester, Y. Leung, N. Li, W. Liauw, B. W. X. Lim, A. Linder, J. Lubinski, S. Mahale, C. Mateoiu, S. McInerny, J. Menkiszak, P. Minoo, S. Mittelstadt, D. Morris, S. Orsulic, S. -Y. Park, C. L. Pearce, J. V. Pearson, M. C. Pike, C. M. Quinn, G. R. Mohan, J. Rao, M. J. Riggan, M. Ruebner, S. Salfinger, C. L. Scott, M. Shah, H. Steed, C .J. R. Stewart, D. Subramanian, S. Sung, K. Tang, P. Timpson, R. L. Ward, R. Wiedenhoefer, H. Thorne, P. A. Cohen, P. Crowe, P. A. Fasching, J. Gronwald, N. J. Hawkins, E. Høgdall, D. G. Huntsman, P. A. James, B. Y. Karlan, L. E. Kelemen, S. Kommoss, G. E. Konecny, F. Modugno, S. K. Park, A. Staebler, K. Sundfeldt, A. H. Wu, A. Talhouk, P. D. P. Pharoah, Lyndal Anderson, A. DeFazio, M. Kobel, M. L. Friedlander, S. J. Ramus, AOCS Group, Australian Pancreatic Genome Initiative, kConFab Investigators

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12 Citations (Scopus)

Abstract

Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primaryMOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and geneexpression 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 ¼ 333), mucinous borderline ovarian tumors (MBOT, n ¼ 151), and upper GI (n ¼ 65) and lower GI tumors (n ¼ 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 ¼ 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 ¼ 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P ¼ 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.
Original languageEnglish
Pages (from-to)5383-5395
Number of pages13
JournalClinical Cancer Research
Volume28
Issue number24
DOIs
Publication statusPublished - 2022

Open Access - Access Right Statement

© 2022 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).

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