Objective Because mucinous carcinomas are rare tumors that affect several organ sites and are known to originate from different tissues, leading to frequent misdiagnoses, the objective was to characterize the differences between primary mucinous tumors of the ovary and metastatic mucinous cancer to the ovary by studying the expression pattern of several candidate biomarkers.
Methods Tissue samples of mucinous histology were obtained between 1985 and 2015. Individual ovary and colon tissue samples were analyzed, including standard (PAX8, CK20, CK7, CDX2, SATB2, estrogen/progesterone) and new (MUC1, MUC5AC) biomarkers, which were then scored for immunoreactivity semi-quantitatively.
Results The study cohort included 98 mucinous tumor samples, including benign mucinous cystadenoma (n=24), mucinous borderline tumors (n=24), mucinous carcinomas (n=40), and metastatic mucinous ovarian carcinomas (n=10). A strong positive correlation was found between PAX8 scoring (p=0.003), CK7 scoring (p=0.0001), and MUC1 scoring (p=0.001) in primary mucinous ovarian cancer. Tumors of increasing invasiveness were analyzed and a significant decrease in the scoring of MUC5AC (p=0.001) was observed, with a stronger expression in adenomas (87%) and borderline tumors (75%), and a lower expression in mucinous cancers (42%). Patients survived significantly longer when their tumors expressed high PAX8 and showed an expansile invasion pattern (p=0.005 and p=0.015, respectively) compared with patients with PAX8-negative tumors and destructive invasion pattern.
Conclusion The study data support the diagnostic value of MUC1 as a new biomarker to differentiate between primary and metastatic mucinous ovarian cancer. In addition, the tumor growth pattern along with the PAX8 immunophenotype might represent potential prognostic biomarkers for primary mucinous ovarian carcinomas.
- ovarian cancer
Data availability statement
Data may be obtained from a third party and are not publicly available.
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Contributors Conception and design: ES. Administrative support: ES, DM, SM. Provision of study materials or patients: ES, DM, SM, FT. Collection and assembly of data: EH. Data analysis and interpretation: EH, ACR, ES, SM, FK, FW, MR, MK, BC, TK. Manuscript writing: ACR, ES. Final approval of manuscript: all authors. ES is responsible for the overall content as the guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests FT: grants, research support, advisory boards, honoraria and travel expenses from AstraZeneca, Clovis, GSK, Medac, MSD, PharmaMar, Roche and Tesaro. SM: grants, research support, advisory boards, honoraria and travel expenses from Abbvie, AstraZeneca, Clovis, Eisai, GSK, MEDAC, MSD, Novartis, OLYMPUS, Europa, Pfizer, PharmaMar, Roche, Sensor Kinesis, Tesaro and Teva.
Provenance and peer review Not commissioned; externally peer reviewed.
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