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, M; 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, MW; Boros, J; Bowtell, DDL; AOCS Group; Brand, AH; Brenton, JD; Campbell, I; Cheasley, D; Cohen, J; Cybulski, C; Elishaev, E; Erber, R; Farrell, R; Fischer, A; Fu, Z; Gilks, B; Gill, AJ; Australian Pancreatic Genome Initiative; 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, JM; Lai, T; Laslavic, A; Lester, J; Leung, Y; Li, N; Liauw, W; Lim, BWX; Linder, A; Lubinski, 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; Ruebner, M; Salfinger, S; Scott, CL; Shah, M; Steed, H; Stewart, CJR; Subramanian, D; Sung, S; Tang, K; Timpson, P; Ward, RL; Wiedenhoefer, R; Thorne, H; kConFab Investigators; Cohen, PA; Crowe, P; Fasching, PA; Gronwald, J; Hawkins, NJ; Hogdall, 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, PDP; Anderson, L; DeFazio, A; Kobel, M; Friedlander, ML; Ramus, SJ

Author(s): Meagher, NS; Gorringe, KL; Wakefield, M; 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, MW; Boros, J; Bowtell, DDL; AOCS Group; Brand, AH; Brenton, JD; Campbell, I; Cheasley, D; Cohen, J; Cybulski, C; Elishaev, E; Erber, R; Farrell, R; Fischer, A; Fu, Z; Gilks, B; Gill, AJ; Australian Pancreatic Genome Initiative; 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, JM; Lai, T; Laslavic, A; Lester, J; Leung, Y; Li, N; Liauw, W; Lim, BWX; Linder, A; Lubinski, 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; Ruebner, M; Salfinger, S; Scott, CL; Shah, M; Steed, H; Stewart, CJR; Subramanian, D; Sung, S; Tang, K; Timpson, P; Ward, RL; Wiedenhoefer, R; Thorne, H; kConFab Investigators; Cohen, PA; Crowe, P; Fasching, PA; Gronwald, J; Hawkins, NJ; Hogdall, 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, PDP; Anderson, L; DeFazio, A; Kobel, M; Friedlander, ML; Ramus, SJ;
Details: Publication Year 2022-12-15,Volume 28,Issue #24,Page 5383-5395
Journal Title: Clinical Cancer Research
Publication Type: Research article
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.
Keywords: Female; Humans; Neoplasm Staging; *Ovarian Neoplasms/metabolism; Carcinoma, Ovarian Epithelial/pathology; *Adenocarcinoma, Mucinous/genetics/diagnosis; Prognosis; *Gastrointestinal Neoplasms/metabolism
Department(s): Laboratory Research; Familial Cancer Centre; Medical Oncology
PubMed ID: 36222710
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-22-1206
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-22-1206
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-01-31 07:02:43

Last Modified: 2025-01-31 07:03:46