TY - JOUR
T1 - Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer
AU - Pore, Milind
AU - Meijer, Coby
AU - de Bock, Geertruida H.
AU - Boersma-van Ek, Wytske
AU - Terstappen, Leon W. M. M.
AU - Groen, Harry J. M.
AU - Timens, Wim
AU - Kruyt, Frank A. E.
AU - Hiltermann, T. Jeroen N.
PY - 2016/11
Y1 - 2016/11
N2 - The prognostic value of markers of cancer stem cells and epithelial to mesenchymal transition in small cell lung cancer is not known. We retrospectively studied these markers in the biopsy tissue of patients with small cell lung cancer and correlated them with overall survival and the strongest known prognostic marker circulating tumor cells.Background: Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and epithelial to mesenchymal transition have been associated with increased chemoresistance and metastatic spread in SCLC. Patients and Methods: The biopsy specimens of 38 SCLC patients were used for marker evaluation by immunohistochemistry. The markers for CSCs were CD44 and SOX2. The markers for epithelial to mesenchymal transition were E-cadherin, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, vimentin, and c-MET. Staining was scored as low (weak) or high (strong) intensity for SOX2, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, and c-MET and using the immunoreactive score for CD44, E-cadherin, and vimentin, expressed as low or high expression. Results: High expression of c-MET (c-METH) and low expression of E-cadherin (E-cad(L)) showed a trend toward a better prognosis (P = .07 and P = .09, respectively). The combination of c-METH and E-cad(L) resulted in significantly better survival (P = .007). The tested markers were not associated with CTCs, although a trend was seen for c-(METE)-E-H-cad(L) (P = .09) with low CTCs. The CSC markers SOX2 and CD44 were not associated with overall survival in this patient cohort. Conclusion: SCLC with a mesenchymal-like phenotype (c-METHE-cad(L)) is associated with longer survival and showed a trend toward lower CTCs. (C) 2016 Elsevier Inc. All rights reserved.
AB - The prognostic value of markers of cancer stem cells and epithelial to mesenchymal transition in small cell lung cancer is not known. We retrospectively studied these markers in the biopsy tissue of patients with small cell lung cancer and correlated them with overall survival and the strongest known prognostic marker circulating tumor cells.Background: Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and epithelial to mesenchymal transition have been associated with increased chemoresistance and metastatic spread in SCLC. Patients and Methods: The biopsy specimens of 38 SCLC patients were used for marker evaluation by immunohistochemistry. The markers for CSCs were CD44 and SOX2. The markers for epithelial to mesenchymal transition were E-cadherin, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, vimentin, and c-MET. Staining was scored as low (weak) or high (strong) intensity for SOX2, epithelial cell adhesion molecule, cytokeratins 8, 18, and 19, and c-MET and using the immunoreactive score for CD44, E-cadherin, and vimentin, expressed as low or high expression. Results: High expression of c-MET (c-METH) and low expression of E-cadherin (E-cad(L)) showed a trend toward a better prognosis (P = .07 and P = .09, respectively). The combination of c-METH and E-cad(L) resulted in significantly better survival (P = .007). The tested markers were not associated with CTCs, although a trend was seen for c-(METE)-E-H-cad(L) (P = .09) with low CTCs. The CSC markers SOX2 and CD44 were not associated with overall survival in this patient cohort. Conclusion: SCLC with a mesenchymal-like phenotype (c-METHE-cad(L)) is associated with longer survival and showed a trend toward lower CTCs. (C) 2016 Elsevier Inc. All rights reserved.
KW - CSCs
KW - CTCs
KW - EMT
KW - c-MET
KW - SCLC
KW - MOLECULAR CHARACTERISTICS
KW - SOX2
KW - EXPRESSION
KW - METASTASIS
KW - TRANSITION
KW - BIOLOGY
KW - CHEMORESISTANCE
KW - NEUROENDOCRINE
KW - MICROEMBOLI
KW - CARCINOMA
U2 - 10.1016/j.cllc.2016.05.015
DO - 10.1016/j.cllc.2016.05.015
M3 - Article
C2 - 27363902
SN - 1525-7304
VL - 17
SP - 535
EP - 542
JO - Clinical lung cancer
JF - Clinical lung cancer
IS - 6
ER -