Milind Pore1, Coby Meijer1, Geertruida H de Bock2, Wytske Boersma-van Ek1, Leon W M M Terstappen3, Harry J M Groen4, Wim Timens5, Frank A E Kruyt1, T Jeroen N Hiltermann6. 1. Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3. Department of Medical Cell Biophysics, University of Twente, Enschede, The Netherlands. 4. Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 5. Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 6. Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: t.j.n.hiltermann@umcg.nl.
Abstract
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-cadL) showed a trend toward a better prognosis (P = .07 and P = .09, respectively). The combination of c-METH and E-cadL resulted in significantly better survival (P = .007). The tested markers were not associated with CTCs, although a trend was seen for c-METHE-cadL (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-cadL) is associated with longer survival and showed a trend toward lower CTCs.
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 SCLCpatients 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-cadL) showed a trend toward a better prognosis (P = .07 and P = .09, respectively). The combination of c-METH and E-cadL resulted in significantly better survival (P = .007). The tested markers were not associated with CTCs, although a trend was seen for c-METHE-cadL (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-cadL) is associated with longer survival and showed a trend toward lower CTCs.
Authors: Marloes A M Peters; Coby Meijer; Rudolf S N Fehrmann; Annemiek M E Walenkamp; Ido P Kema; Elisabeth G E de Vries; Harry Hollema; Sjoukje F Oosting Journal: Pathol Oncol Res Date: 2019-09-02 Impact factor: 3.201