Prognostic Significance of MUC-1 in Circulating Tumor Cells in Patients With Metastatic Pancreatic Adenocarcinoma

Abstract

Objectives-Development of targeted therapies for pancreatic cancer could be enhanced by a reliable method for noninvasive tumor cell assessment. In this pilot study we isolated and phenotypically characterized circulating tumor cells (CTC) from patients with metastatic pancreatic cancer and explored their relationship to clinical outcome.Methods-Peripheral blood from 50 patients was collected at treatment initiation and first disease evaluation for CTC enumeration and phenotyping by CellSearch® system. Expression of human mucin 1 (MUC-1) was performed.Results-48 and 37 patients had evaluable samples at baseline and first disease evaluation, respectively. The cohort was 62% male, with a median age of 63 years. At least 1 CTC/7.5mL was detected in 23 patients (48%) pre-treatment and 11 patients (30%) at first disease evaluation. No difference was seen in overall survival between patients with ≥ 1 CTC vs no CTC at baseline (p=0.14). Patients with MUC-1 expressing CTC (n=10) had shorter median overall survival compared to those with MUC-1 negative CTC (n=13) (2.7 vs. 9.6m; p=0.044).Conclusions-CTC enumeration and phenotypic characterization from metastatic pancreatic cancer patients is feasible. No correlation was found between CTC isolation and survival. However, the presence of MUC-1 expressing CTC demonstrated a trend toward inferior survival.

Circulating Tumor Cells and Cell-Free DNA in Pancreatic Ductal Adenocarcinoma

“…This may lead to an understanding of the malignant potential of CTCs captured and add to the benefit of using CTCs as prognostic biomarkers. Dotan et al 30 were able to measure MUC-1 from the CTCs captured by the CellSearch system. Increased MUC-1 tumor expression is associated with a poorer outcome in PDAC, 46 and the presence of antieMUC-1 IgG antibodies correlates with improved survival.…”

Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

“…Evidence suggests that MUC expression is involved in the invasion and metastasis of various malignancies, including gallbladder cancer [19], breast cancer [20], ovarian cancer [21], gastric carcinoma [22,23], pancreatic carcinoma [24][25][26], ampullary cancer [27,28], lung cancer [16,29], prostate cancer [30], renal cell carcinoma [31], and appendiceal carcinoma [32]. However, the prognostic value of MUC expression in CRC remains controversial [33][34][35][36][37].…”

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

“…Dotan et al evaluated 23 patients with metastasis who had at least one CTC detected at baseline by using CellSearch Ò . They assessed for the expression of MUC-1, which play a role of inducing EMT: MUC-1 expression was observed in 43% (10/ 23) of the patients, and patients with CTCs positive for MUC-1 had shorter median OS than those with CTCs negative for MUC-1 (2.7 months vs. 9.6 months, P = 0.044) (Dotan et al, 2016). Another study, which compared epithelial CTCs and mesenchymal-like CTCs using a vimentin marker, was discussed above (Poruk et al, 2016).…”