Circulating Tumor Cells and EpCAM Expression in Neuroendocrine Tumors

Clinical Cancer Research - Tập 17 Số 2 - Trang 337-345 - 2011
Mohid S. Khan1, Theodora Tsigani1, Mohammed Rashid1, Jeremy S. Rabouhans1, Dominic Yu1, Tu Vinh Luong1, Martyn Caplin1, Tim Meyer1
1Authors' Affiliations: 1Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, 2UCL Cancer Institute, University College London, and Departments of 3Radiology, 4Pathology, and 5Oncology, Royal Free Hospital, London, United Kingdom

Tóm tắt

Abstract Purpose: Neuroendocrine tumors (NET) are heterogeneous tumors with widely variable survival. It is unknown whether they express EpCAM (epithelial cell adhesion molecule) and thus whether NET circulating tumor cells (CTC) are detectable. We systematically investigated EpCAM expression and CTC detection in patients with metastatic NETs and evaluated the potential of CTCs to predict radiological progression. Experimental Design: EpCAM protein expression was evaluated in 74 samples of formalin-fixed, paraffin-embedded NET tissue by immunohistochemistry. Seventy-nine patients with metastatic NETs (42 midgut, 5 unknown primary, 19 pancreatic, 13 bronchopulmonary) had blood samples drawn for CTC isolation and enumeration utilizing the CellSearch platform. Patients were classified as having progressive or nonprogressive disease on the basis of serial imaging. Results: Strong homogeneous, membranous EpCAM expression was observed in all ileal (n = 26) and pancreatic NETs (n = 16), whereas variable EpCAM expression was observed in bronchopulmonary NETs (n = 13). Forty-three percent of midgut and 21% of pancreatic NETs had CTCs detected with a range of 0–62 and 0–11, respectively. The absence of CTCs was strongly associated with stable disease (P < 0.001). There was a moderate correlation between CTC levels and urinary 5-hydroxyindole acetic acid (r = 0.5, P = 0.007) and between CTC levels and burden of liver metastases (B = 8.91, P < 0.001). There was no or low correlation between CTC levels and Ki-67 (r = 0.08, P = 0.59) and serum chromogranin A (r = 0.246, P = 0.03). Conclusions: This is the first systematic analysis showing EpCAM expression and CTC detection in NETs. CTCs seem to be associated with progressive disease and may provide useful prognostic information given the variable survival rates in these tumors. Clin Cancer Res; 17(2); 337–45. ©2011 AACR.

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Clinical Cancer Research

Tập 17 Số 2

337-345

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