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Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes
- Source :
- Meagher, N S, Gorringe, K L, Wakefield, M J, Bolithon, A, Pang, C N I, Chiu, D S, Anglesio, M S, Mallitt, K, Doherty, J A, Harris, H R, Schildkraut, J M, Berchuck, A, Cushing-haugen, K L, Chezar, K, Chou, A, Tan, A, Alsop, J, Barlow, E, Beckmann, M W, Boros, J, Bowtell, D D, Brand, A H, Brenton, J D, Campbell, I, Cheasley, D, Cohen, J, Cybulski, C, Elishaev, E, Erber, R, Farrell, R, Fischer, A, Fu, Z, Gilks, B, Gill, A J, Gourley, C, Grube, M, Harnett, P, Hartmann, A, Hettiaratchi, A, Høgdall, C K, Huzarski, T, Jakubowska, A, Jimenez-linan, M, Kennedy, C J, Kim, B, Kim, J, Kim, J, Klett, K, Koziak, J, Lai, T, Laslavic, A, Lester, J, Leung, Y, Li, N, Liauw, W, Lim, B W X, Linder, A, Lubinski, J, Mahale, S, Mateoiu, C, Mcinerny, S, Menkiszak, J, Minoo, P, Mittelstadt, S, Morris, D, Orsulic, S, Park, S Y, Pearce, C L, Pearson, J V, Pike, M C, Quinn, C M, Mohan, G R, Rao, J, Riggan, M J, Ruebner, M, Salfinger, S, Scott, C L, Shah, M, Steed, H, Stewart, C J R, Subramanian, D, Sung, S, Tang, K, Timpson, P, Ward, R L, Wiedenhoefer, R, Thorne, H, Cohen, P A, Crowe, P, Fasching, P A, Gronwald, J, Hawkins, N J, Høgdall, E, Huntsman, D G, James, P A, Karlan, B Y, Kelemen, L E, Kommoss, S, Konecny, G E, Modugno, F, Park, S K, Staebler, A, Sundfeldt, K, Wu, A H, Talhouk, A, Pharoah, P D P, Anderson, L, Defazio, A, Köbel, M, Friedlander, M L & 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 . https://doi.org/10.1158/1078-0432.CCR-22-1206, https://doi.org/10.1158/1078-0432.CCR-22-1206, AOCS Grp, Australian Pancreatic Genome Initi & kConFab Investigators 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, vol. 28, no. 24, pp. 5383-5395 . https://doi.org/10.1158/1078-0432.CCR-22-1206
- Publication Year :
- 2022
- Publisher :
- American Association for Cancer Research (AACR), 2022.
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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.
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....68e7e60454f3d65c0cafb4f51f254763