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. 2015 Feb;9(2):503-12.
doi: 10.1016/j.molonc.2014.10.005. Epub 2014 Oct 22.

Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours

Sara Ricardo  1 , Lara Marcos-Silva  2 , Daniela Pereira  1 , Rita Pinto  1 , Raquel Almeida  3 , Ola Söderberg  4 , Ulla Mandel  5 , Henrik Clausen  5 , Ana Felix  6 , Nuno Lunet  7 , Leonor David  8
Affiliations

Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours

Sara Ricardo et al. Mol Oncol. 2015 Feb.

Abstract

The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions, in both series. An even better yield was obtained based on positivity for any of the four glyco-mucin profiles, further increasing sensitivity to 72% and 83% in the two series, respectively, with 100% specificity. The strategy is designated glyco-mucin profiling and provides strong support for development of PLA-based serum assays for early diagnosis.

Keywords: Glyco-mucin profile; MUC1; MUC16; Ovarian cancer; Proximity ligation assay.

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Figures

Figure 1
Figure 1
Flow chart of the study. The initial series (CHSJ Porto) consisted of 66 serous ovarian tumours in which we performed Proximity Ligation Assays (PLA) to define the glyco‐mucin profiles. To validate the results, PLA to the same glycol‐mucin pairs was performed in 89 serous ovarian tumours from another institution (IPO Lisbon).
Figure 2
Figure 2
Glyco‐mucin profile of ovarian tumours in CHSJ Porto series. Examples of brightfield PLAs in adenocarcinomas and borderline lesions. The brown dots represent proximity signals between mucin/carbohydrate pairs, namely MUC16/Tn, MUC1/Tn, MUC16/STn and MUC1/ST.
Figure 3
Figure 3
Glyco‐mucin signatures obtained by PLA (Green = Negative; Red = Positive): (A) Representation of PLA results in the 66 ovarian tumours of CHSJ Porto series; (B) Representation of PLA results in the 89 ovarian tumours of IPO Lisbon series. The two columns on the right depict combinations for PLA pairs.
See this image and copyright information in PMC

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