Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes.

Meagher NS, Gorringe KL, Wakefield MJ, Bolithon A, Pang CNI, Chiu DS, Anglesio MS, Mallitt KA, Doherty JA, Harris HR, Schildkraut JM, Berchuck A, Cushing-Haugen KL, Chezar K, Chou A, Tan A, Alsop J, Barlow E, Beckmann M, Boros J, Bowtell DD, Brand AH, Brenton JD, Campbell IM, Cheasley D, Cohen J, Cybulski C, Elishaev E, Erber R, Farrell R, Fischer A, Fu Z, Gilks BC, Gill A, Gourley C, Grube M, Harnett PR, Hartmann A, Hettiaratchi A, Hogdall CK, Huzarski T, Jakubowska A, Jimenez-Linan M, Kennedy CJ, Kim BG, Kim JW, Kim JH, Klett K, Koziak J, Lai T, Laslavic A, Lester J, Leung Y, Li N, Liauw W, Lim BW, Linder A, Lubiński J, Mahale S, Mateoiu C, McInerny S, Menkiszak J, Minoo P, Mittelstadt S, Morris D, Orsulic S, Park SY, Pearce CL, Pearson JV, Pike MC, Quinn CM, Mohan GR, Rao J, Riggan MJ, Rübner M, Salfinger SG, Scott CL, Shah M, Steed H, Stewart CJR, Subramanian D, Sung S, Tang K, Timpson P, Ward R, Wiedenhoefer R, Thorne H, Cohen PA, Crowe PJ, Fasching P, Gronwald J, Hawkins NJ, Høgdall E, Huntsman DG, James PA, Karlan BY, Kelemen LE, Kommoss S, Konecny GE, Modugno F, Park SK, Staebler A, Sundfeldt K, Wu AH, Talhouk A, Pharoah PD, Anderson L, Defazio A, Köbel M, Friedlander M, Ramus SJ (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 28

Pages Range: 5383-5395

Journal Issue: 24

DOI: 10.1158/1078-0432.CCR-22-1206

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 with CRIS profile

Involved external institutions

Emory University United States (USA) (US) University of Calgary Canada (CA) University of British Columbia Canada (CA) Peter MacCallum Cancer Centre Australia (AU) Duke University Medical Center United States (USA) (US) University of New South Wales (UNSW) Australia (AU) University of Sydney (USYD) Australia (AU) Universitätsklinikum Tübingen Germany (DE) West Pomeranian University of Technology Szczecin / Zachodniopomorski Uniwersytet Technologiczny w Szczecinie (ZUT) Poland (PL) University of Cambridge United Kingdom (GB) Alberta Health Services (AHS) Canada (CA) Royal Hospital for Women Australia (AU) University of Edinburgh United Kingdom (GB) University of Copenhagen Denmark (DK) Addenbrooke's Hospital United Kingdom (GB) University of Western Australia (UWA) Australia (AU) University of California Irvine United States (USA) (US) University of Gothenburg / Göteborgs universitet Sweden (SE) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Australian National University (ANU) Australia (AU) University of California Los Angeles (UCLA) United States (USA) (US) University of Alberta Canada (CA) University of Southern California (USC) United States (USA) (US) National Cancer Center (NCC) / 국립암센터 Korea, Republic of (KR) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Eberhard Karls Universität Tübingen Germany (DE) British Columbia Cancer Agency Canada (CA) St John of God Health Care Australia (AU) Fred Hutchinson Cancer Research Center Canada (CA) UPMC Hillman Cancer Center United States (USA) (US) Keck School of Medicine of USC United States (USA) (US) University of Pittsburgh United States (USA) (US) Yonsei University Korea, Republic of (KR) Sungkyunkwan University (SKKU) Korea, Republic of (KR) Garvan Institute of Medical Research Australia (AU) Duke University United States (USA) (US) Houston Texas Medical Center United States (USA) (US) Walter and Eliza Hall Institute of Medical Research (WEHI) Australia (AU) Prince of Wales Hospital (POWH) Australia (AU) Westmead Institute for Medical Research Australia (AU) Medical University of South Carolina (MUSC) United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Kinghorn Cancer Centre Australia (AU)

How to cite

APA:

Meagher, N.S., Gorringe, K.L., Wakefield, M.J., Bolithon, A., Pang, C.N.I., Chiu, D.S.,... Ramus, S.J. (2022). Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes. Clinical Cancer Research, 28(24), 5383-5395. https://doi.org/10.1158/1078-0432.CCR-22-1206

MLA:

Meagher, Nicola S., et al. "Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes." Clinical Cancer Research 28.24 (2022): 5383-5395.

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