Dataset Information

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

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.

SUBMITTER: Meagher NS

PROVIDER: S-EPMC9751776 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Meagher Nicola S NS Gorringe Kylie L KL Wakefield Matthew M Bolithon Adelyn A Pang Chi Nam Ignatius CNI Chiu Derek S DS Anglesio Michael S MS Mallitt Kylie-Ann KA Doherty Jennifer A JA Harris Holly R HR Schildkraut Joellen M JM Berchuck Andrew A Cushing-Haugen Kara L KL Chezar Ksenia K Chou Angela A Tan Adeline A Alsop Jennifer J Barlow Ellen E Beckmann Matthias W MW Boros Jessica J Bowtell David D L DDL Brand Alison H AH Brenton James D JD Campbell Ian I Cheasley Dane D Cohen Joshua J Cybulski Cezary C Elishaev Esther E Erber Ramona R Farrell Rhonda R Fischer Anna A Fu Zhuxuan Z Gilks Blake B Gill Anthony J AJ Gourley Charlie C Grube Marcel M Harnett Paul R PR Hartmann Arndt A Hettiaratchi Anusha A Høgdall Claus K CK Huzarski Tomasz T Jakubowska Anna A Jimenez-Linan Mercedes M Kennedy Catherine J CJ Kim Byoung-Gie BG Kim Jae-Weon JW Kim Jae-Hoon JH Klett Kayla K Koziak Jennifer M JM Lai Tiffany T Laslavic Angela A Lester Jenny J Leung Yee Y Li Na N Liauw Winston W Lim Belle W X BWX Linder Anna A Lubiński Jan J Mahale Sakshi S Mateoiu Constantina C McInerny Simone S Menkiszak Janusz J Minoo Parham P Mittelstadt Suzana S Morris David D Orsulic Sandra S Park Sang-Yoon SY Pearce Celeste Leigh CL Pearson John V JV Pike Malcolm C MC Quinn Carmel M CM Mohan Ganendra Raj GR Rao Jianyu J Riggan Marjorie J MJ Ruebner Matthias M Salfinger Stuart S Scott Clare L CL Shah Mitul M Steed Helen H Stewart Colin J R CJR Subramanian Deepak D Sung Soseul S Tang Katrina K Timpson Paul P Ward Robyn L RL Wiedenhoefer Rebekka R Thorne Heather H Cohen Paul A PA Crowe Philip P Fasching Peter A PA Gronwald Jacek J Hawkins Nicholas J NJ Høgdall Estrid E Huntsman David G DG James Paul A PA Karlan Beth Y BY Kelemen Linda E LE Kommoss Stefan S Konecny Gottfried E GE Modugno Francesmary F Park Sue K SK Staebler Annette A Sundfeldt Karin K Wu Anna H AH Talhouk Aline A Pharoah Paul D P PDP Anderson Lyndal L DeFazio Anna A Köbel Martin M Friedlander Michael L ML Ramus Susan J SJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20221201 24

<h4>Purpose</h4>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.<h4>Experimental design</h4>Discovery analyses selected 19 genes with prognostic/diagnostic potentia ...[more]

PMID: 36222710

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Project description:BackgroundThe vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC).MethodsImmunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases.ResultsAmong 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively.ConclusionClaudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

Dataset Information

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

Purpose

Experimental design

Results

Conclusions

Publications

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

Similar Datasets

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