Rationale and feasibility of mucin expression profiling by qRT-PCR as diagnostic biomarkers in cytology specimens of pancreatic cancer.

BACKGROUND: Aberrantly expressed mucin glycoproteins (MUC) play important roles in pancreatic ductal adenocarcinoma (PDAC), yet their use as a diagnostic aid in fine-needle aspiration biopsy (FNAB) is poorly documented. The aim of this study was to investigate the rationale and feasibility of mucin (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6) expression profiling by RT-PCR for diagnostic applications in cytology. METHODS: Mucin expression was examined by RT-PCR and immunohistochemistry in specimens resected from patients with pancreatic (n = 101), ampullary (n = 23), and common bile duct (n = 10) cancers and 33 with chronic pancreatitis. Furthermore, mucin profiling by RT-PCR was prospectively compared in surgical and biopsy specimens of 40 patients with pancreatic solid tumours qualified for FNAB prior to surgery. RESULTS: A logistic regression model to distinguish PDAC from chronic pancreatitis using RT-PCR profiling included MUC3, MUC5AC, and MUC6. The same set of mucins differentiated ampullary and bile duct cancers from chronic pancreatitis. AUCs for the ROC curves derived from the two models were 0.95 (95%CI 0.87-0.99) and 0.92 (95%CI 0.81-0.98), respectively. The corresponding positive likelihood ratios were 6.02 and 5.97, while the negative likelihood ratios were 0.10 and 0.12. AUCs of ROC curves obtained by RT-PCR and immunohistochemistry demonstrated that both analytical methods were comparable. Surgical and cytological samples showed significantly correlated values of ΔCt for individual mucins with the overall Pearson's correlation coefficient r = 0.841 (P = 0.001). CONCLUSIONS: Mucin expression profiling of pancreatic cancer with RT-PCR is feasible and may be a valuable help in discriminating malignant lesions from chronic pancreatitis in FNAB cytology.