TY - JOUR

T1 - Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

AU - Meagher, Nicola S.

AU - Gorringe, Kylie L.

AU - Wakefield, Matthew

AU - Bolithon, Adelyn

AU - Pang, Chi Nam Ignatius

AU - Chiu, Derek S.

AU - Anglesio, Michael S.

AU - Mallitt, Kylie-Ann

AU - Doherty, Jennifer A.

AU - Harris, Holly R.

AU - Schildkraut, Joellen M.

AU - Berchuck, Andrew

AU - Cushing-Haugen, Kara L.

AU - Chezar, Ksenia

AU - Chou, Angela

AU - Tan, Adeline

AU - Alsop, Jennifer

AU - Barlow, Ellen

AU - Beckmann, Matthias W.

AU - Boros, Jessica

AU - Bowtell, David D. L.

AU - Brand, Alison H.

AU - Brenton, James D.

AU - Campbell, Ian

AU - Cheasley, Dane

AU - Cohen, Joshua

AU - Cybulski, Cezary

AU - Elishaev, Esther

AU - Erber, Ramona

AU - Farrell, Rhonda

AU - Fischer, Anna

AU - Fu, Zhuxuan

AU - Gilks, Blake

AU - Gill, Anthony J.

AU - Gourley, Charlie

AU - Grube, Marcel

AU - Harnett, Paul R.

AU - Hartmann, Arndt

AU - Hettiaratchi, Anusha

AU - Hogdall, Claus K.

AU - Huzarski, Tomasz

AU - Jakubowska, Anna

AU - Jimenez-Linan, Mercedes

AU - Kennedy, Catherine J.

AU - Kim, Byoung-Gie

AU - Kim, Jae-Weon

AU - Kim, Jae-Hoon

AU - Klett, Kayla

AU - Hogdall, Estrid

AU - AOCS Grp

AU - Australian Pancreatic Genome Initi

AU - kConFab Investigators

PY - 2022

Y1 - 2022

N2 - 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 = 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.

AB - 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 = 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.

KW - INTESTINAL-TYPE

KW - BORDERLINE TUMORS

KW - POOR-PROGNOSIS

KW - ADENOCARCINOMA

KW - CARCINOMA

KW - TRANSGELIN

KW - EXPANSILE

KW - PATTERN

KW - CANCER

KW - RARE

U2 - 10.1158/1078-0432.CCR-22-1206

DO - 10.1158/1078-0432.CCR-22-1206

M3 - Journal article

C2 - 36222710

VL - 28

SP - 5383

EP - 5395

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 24

ER -