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A combination of immunohistochemical markers, MUC1, MUC5AC, PAX8 and growth pattern for characterization of mucinous neoplasm of the ovary
  1. Anca Chelariu-Raicu1,
  2. Eva Holley2,
  3. Doris Mayr2,
  4. Frederick Klauschen2,
  5. Fabienne Wehweck2,
  6. Miriam Rottmann3,
  7. Mirjana Kessler1,
  8. Till Kaltofen1,
  9. Bastian Czogalla1,
  10. Fabian Trillsch1,
  11. Sven Mahner1 and
  12. Elisa Schmoeckel2
  1. 1 Department of Obstetrics and Gynecology, University Hospital, Ludwig Maximilians University Munich, Munich, Bayern, Germany
  2. 2 Institute of Pathology, Munich, Germany
  3. 3 Institute for Medical Information Processing, Biometry and Epidemiology, Munich, Germany
  1. Correspondence to Dr Elisa Schmoeckel, Institute of Pathology, Munich, Germany; Elisa.Schmoeckel{at}med.uni-muenchen.de

Abstract

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.

  • gynecology
  • cystadenocarcinoma
  • mucinous
  • ovarian cancer

Data availability statement

Data may be obtained from a third party and are not publicly available.

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Data availability statement

Data may be obtained from a third party and are not publicly available.

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Footnotes

  • 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.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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