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Mucins MUC16 and MUC1 are major carriers of SLea and SLex in borderline and malignant serous ovarian tumors

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Abstract

Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewisa (SLea), and sialyl Lewisx (SLex) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLea and SLex are MUC16 and/or MUC1 (100 and 92 % for SLea and 64 and 70 % for SLex, respectively). In cystadenomas, SLea and SLex are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLea and SLex in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.

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Acknowledgments

The authors thank Joyce Taylor-Papadimitriou and Joy Burchell for their kind offer of antibody HMRG2. The authors also thank Fátima Carneiro, Director of the Department of Pathology of Centro Hospitalar S. João, for the easy access to archived material.

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Authors and Affiliations

  1. IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

    Sara Ricardo, Lara Marcos-Silva, Ricardo Coelho & Leonor David

  2. Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal

    Sara Ricardo, Lara Marcos-Silva, Ricardo Coelho & Leonor David

  3. Faculty of Medicine of the University of Porto, Porto, Portugal

    Sara Ricardo, Cristina Valente, Ricardo Coelho & Leonor David

  4. Oncology Department of Centro Hospitalar S. João, Porto, Portugal

    Rosa Gomes

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  1. Sara Ricardo
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Correspondence to Sara Ricardo.

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The authors have no conflict of interest and no competing interests.

Grant support

Support by Programa Operacional Ciência e Inovação 2010 do Quadro Comunitário de Apoio III and FEDER (PTDC/SAU-ONC/117,216/2010). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and partially supported by FCT. Project NORTE-07-0124-FEDER-000,024 co-financed by Programa Operacional Regional do Norte (ON.2–O Novo Norte), under Quadro de Referência Estratégico Nacional (QREN), by Fundo Europeu de Desenvolvimento Regional (FEDER). Sara Ricardo acknowledges FCT for financial support through Post-Doc fellowship (SFRH/BPD/100358/2014).

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Sara Ricardo and Lara Marcos-Silva contributed equally to the work.

Electronic supplementary material

Supplementary Fig. 1

Kaplan-Meier plots representing overall survival results for 14 serous ovarian adenocarcinoma cases, defined according to SLea and SLex patterns of expression and PLA results for MUC16/SLea, MUC1/SLea, MUC16/SLex, and MUC1/SLex. No significant difference was observed (GIF 37 kb)

High-resolution image (EPS 82,963 kb)

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Ricardo, S., Marcos-Silva, L., Valente, C. et al. Mucins MUC16 and MUC1 are major carriers of SLea and SLex in borderline and malignant serous ovarian tumors. Virchows Arch 468, 715–722 (2016). https://doi.org/10.1007/s00428-016-1929-6

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