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MUC13 - An Early Diagnostic Marker for Pancreatic Ductal Adenocarcinoma
Sheema Khan3, Stephen W. Behrman*1, Nadeem Zafar2, Meena Jaggi3, Subhash C. Chauhan3
1Surgery, Univ. of Tennessee, Memphis, TN; 2Pathology, University of Tennessee Health Science Center, Memphis, TN; 3Pharmaceutical Sciences, Univ. of Tennessee HSC, Memphis, TN
Background: Pancreatic Ductal Adenocarcinoma (PDAC) is the 4th leading cause of cancer related death in the United States. PDAC typically has a very poor survival rate due to late diagnosis. New approaches that could aid in early diagnosis would be highly desirable. MUC13 is a recently identified high molecular weight glycoprotein that is aberrantly expressed in PDAC via alterations of multiple signaling pathways. In order to assess its role in early cancer diagnosis we examined the expression of the MUC13 in the non-invasive precursor lesions, pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues.
Methods: Tissue microarrays prepared from formalin-fixed, paraffin-embedded specimens of human PDAC were assessed for expression of MUC13 using our own laboratory generated anti-MUC13 mouse monoclonal antibody (MAb) and analyzed by immunohistofluorescence/immunohistochemistry techniques following Mean Composite Score (MCS) as a semi quantitative method.
Results: MUC13 is not present in normal pancreas but was detected in 100% (n=28) of PanIN lesions. MUC13 expression was detected in 213 of 225 (94.6%) stage I-IV PDAC samples compared with very low or no expression in adjacent normal tissues. High intensity of MUC13 expression was associated with moderate to poorly differentiated tumors. There was a significant difference in the subcellular localization of MUC13 (higher cytoplasmic versus nuclear expression): the percentage of samples positive for nuclear staining was higher in PDAC (83.5%) as compared to PanINs (46.4%) and tumor adjacent normal tissues (33%). Higher MUC13 expression (overall and nuclear) was positively associated with nodal metastasis. In addition, increased nuclear expression of MUC13 correlated with poor overall survival. There was high specificity of MUC13 in pancreatic ductal adenocarcinoma (Mean composite score: MCS=9.7) as compared to normal pancreas (MCS≤ 1), adenosquamous carcinoma (n=18, MCS=1.2) and neuroendocrine carcinoma (n=5, MCS=0.4).
Conclusion: MUC13 is highly expressed in PDAC and can be detected in formalin-fixed paraffin-embedded human tissues using our novel anti-MUC13 MAb. The findings from this study suggest that MUC13 expression and and its site of subcellular localization offer a potential early diagnostic and prognostic marker in PDAC.
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