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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

Authors
 Nicola S Meagher  ;  Kylie L Gorringe  ;  Matthew Wakefield  ;  Adelyn Bolithon  ;  Chi Nam Ignatius Pang  ;  Derek S Chiu  ;  Michael S Anglesio  ;  Kylie-Ann Mallitt  ;  Jennifer A Doherty  ;  Holly R Harris  ;  Joellen M Schildkraut  ;  Stefan Kommoss  ;  Gottfried E Konecny  ;  Francesmary Modugno  ;  Sue K Park  ;  Annette Staebler  ;  Karin Sundfeldt  ;  Anna H Wu  ;  Aline Talhouk  ;  Paul D P Pharoah  ;  Lyndal Anderson  ;  Andrew Berchuck  ;  Anna DeFazio  ;  Martin Köbel  ;  Michael L Friedlander  ;  Susan J Ramus  ;  Kara L Cushing-Haugen  ;  Ksenia Chezar  ;  Angela Chou  ;  Adeline Tan  ;  Jennifer Alsop  ;  Ellen Barlow  ;  Matthias W Beckmann  ;  Jessica Boros  ;  David D L Bowtell  ;  AOCS Group  ;  Alison H Brand  ;  James D Brenton  ;  Ian Campbell  ;  Dane Cheasley  ;  Joshua Cohen  ;  Cezary Cybulski  ;  Esther Elishaev  ;  Ramona Erber  ;  Rhonda Farrell  ;  Anna Fischer  ;  Zhuxuan Fu  ;  Blake Gilks  ;  Anthony J Gill  ;  Australian Pancreatic Genome Initiative  ;  Charlie Gourley  ;  Marcel Grube  ;  Paul R Harnett  ;  Arndt Hartmann  ;  Anusha Hettiaratchi  ;  Claus K Høgdall  ;  Tomasz Huzarski  ;  Anna Jakubowska  ;  Mercedes Jimenez-Linan  ;  Catherine J Kennedy  ;  Byoung-Gie Kim  ;  Jae-Weon Kim  ;  Jae-Hoon Kim  ;  Kayla Klett  ;  Jennifer M Koziak  ;  Tiffany Lai  ;  Angela Laslavic  ;  Jenny Lester  ;  Yee Leung  ;  Na Li  ;  Winston Liauw  ;  Belle W X Lim  ;  Anna Linder  ;  Jan Lubiński  ;  Sakshi Mahale  ;  Constantina Mateoiu  ;  Simone McInerny  ;  Janusz Menkiszak  ;  Parham Minoo  ;  Suzana Mittelstadt  ;  David Morris  ;  Sandra Orsulic  ;  Sang-Yoon Park  ;  Celeste Leigh Pearce  ;  John V Pearson  ;  Malcolm C Pike  ;  Carmel M Quinn  ;  Ganendra Raj Mohan  ;  Jianyu Rao  ;  Marjorie J Riggan  ;  Matthias Ruebner  ;  Stuart Salfinger  ;  Clare L Scott  ;  Mitul Shah  ;  Helen Steed  ;  Colin J R Stewart  ;  Deepak Subramanian  ;  Soseul Sung  ;  Katrina Tang  ;  Paul Timpson  ;  Robyn L Ward  ;  Rebekka Wiedenhoefer  ;  Heather Thorne  ;  kConFab Investigators  ;  Paul A Cohen  ;  Philip Crowe  ;  Peter A Fasching  ;  Jacek Gronwald  ;  Nicholas J Hawkins  ;  Estrid Høgdall  ;  David G Huntsman  ;  Paul A James  ;  Beth Y Karlan  ;  Linda E Kelemen 
Citation
 CLINICAL CANCER RESEARCH, Vol.28(24) : 5383-5395, 2022-12 
Journal Title
CLINICAL CANCER RESEARCH
ISSN
 1078-0432 
Issue Date
2022-12
MeSH
Adenocarcinoma, Mucinous* / diagnosis ; Adenocarcinoma, Mucinous* / genetics ; Carcinoma, Ovarian Epithelial / pathology ; Female ; Gastrointestinal Neoplasms* / metabolism ; Humans ; Neoplasm Staging ; Ovarian Neoplasms* / metabolism ; Prognosis
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.
Files in This Item:
T9992022832.pdf Download
DOI
10.1158/1078-0432.CCR-22-1206
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193926
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