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 -