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

Authors :
Susan J. Ramus
Michael L. Friedlander
Martin Köbel
Anna DeFazio
Lyndal Anderson
Paul D.P. Pharoah
Aline Talhouk
Anna H. Wu
Karin Sundfeldt
Annette Staebler
Sue K. Park
Francesmary Modugno
Gottfried E. Konecny
Stefan Kommoss
Linda E. Kelemen
Beth Y. Karlan
Paul A. James
David G. Huntsman
Estrid Høgdall
Nicholas J. Hawkins
Jacek Gronwald
Peter A. Fasching
Philip Crowe
Paul A. Cohen
Heather Thorne
Rebekka Wiedenhoefer
Robyn L. Ward
Paul Timpson
Katrina Tang
Soseul Sung
Deepak Subramanian
Colin J.R. Stewart
Helen Steed
Mitul Shah
Clare L. Scott
Stuart Salfinger
Matthias Ruebner
Marjorie J. Riggan
Jianyu Rao
Ganendra Raj Mohan
Carmel M. Quinn
Malcolm C. Pike
John V. Pearson
Celeste Leigh Pearce
Sang-Yoon Park
Sandra Orsulic
David Morris
Suzana Mittelstadt
Parham Minoo
Janusz Menkiszak
Simone McInerny
Constantina Mateoiu
Sakshi Mahale
Jan Lubiński
Anna Linder
Belle W.X. Lim
Winston Liauw
Na Li
Yee Leung
Jenny Lester
Angela Laslavic
Tiffany Lai
Jennifer M. Koziak
Kayla Klett
Jae-Hoon Kim
Jae-Weon Kim
Byoung-Gie Kim
Catherine J. Kennedy
Mercedes Jimenez-Linan
Anna Jakubowska
Tomasz Huzarski
Claus K. Høgdall
Anusha Hettiaratchi
Arndt Hartmann
Paul R. Harnett
Marcel Grube
Charlie Gourley
Anthony J. Gill
Blake Gilks
Zhuxuan Fu
Anna Fischer
Rhonda Farrell
Ramona Erber
Esther Elishaev
Cezary Cybulski
Joshua Cohen
Dane Cheasley
Ian Campbell
James D. Brenton
Alison H. Brand
David D.L. Bowtell
Jessica Boros
Matthias W. Beckmann
Ellen Barlow
Jennifer Alsop
Adeline Tan
Angela Chou
Ksenia Chezar
Kara L. Cushing-Haugen
Andrew Berchuck
Joellen M. Schildkraut
Holly R. Harris
Jennifer A. Doherty
Kylie-Ann Mallitt
Michael S. Anglesio
Derek S. Chiu
Chi Nam Ignatius Pang
Adelyn Bolithon
Matthew Wakefield
Kylie L. Gorringe
Nicola S. Meagher
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

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

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....9bcad0fe969c428ac7e34a902af89649