Abstract
BackgroundMucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival.MethodsPatients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0.ResultsSerum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease.Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression.ConclusionsThis study found significantly elevated Mucin-1 serum concentrations in ovarian carcinoma patients as compared to those women suffering from benign ovarian diseases. However, it needs to be noted that Mucin-1 concentrations in carcinoma patients showed a rather high variability. Results from immunohistochemistry indicate that Mucin-1 has a prognostic relevance in ovarian carcinomas when evaluating the expression by VU4H5 antibody.
Highlights
Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29
The extent of the primary tumour is defined according to the Union for International Cancer Control (UICC): pT1= the tumour is limited to the ovaries, pT2= the tumour has spread to the pelvis, pT3= the tumour has spread beyond the pelvis and/or to regional lymphnodes
The correlation of the staining results for both antibodies with tumour grade, Federation of Gynaecologists and Obstetricians (FIGO) stage and pT-stage revealed results of varying significance: With respect to tumour grade we found a positive relationship between the tumour feature and MUC1 when samples were evaluated for VU4H5 (p=0.003), see Figure 3, but not for VU3C6 (p=0.104)
Summary
Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. Monoclonal antibodies which are specific for the different tandem repeat units in the protein core of the MUC1 antigen are used in these kits and automated analysers produce results that are reliable [8]. Both markers are structurally similar and CA 15–3 is routinely utilised as a diagnostic and prognostic marker in breast cancer [9,10]. Published data confirmed this assumption [13], but the diagnostic relevance for patients with ovarian tumours of uncertain dignity remains unclear
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