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Clinical Relevance of Cd133 Positive Cells in Locally Advanced Non-Small Cell Lung Cancer
Annals of Oncology 25 (Supplement 4): iv417–iv425, 2014 doi:10.1093/annonc/mdu348.17
NSCLC, locally advanced 1211P
CLINICAL RELEVANCE OF CD133 POSITIVE CELLS IN LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER
abstracts
Aim: CD133 positive cells have been identified as tumor initiating cells in non-small cell lung cancer (NSCLC) and have been shown to be resistant to conventional cytotoxic chemotherapy in experimental studies, suggesting a possible role in chemoresistance and disease relapse. However their prognostic relevance in the context of clinical treatment of NSCLC has not been fully investigated.
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv422/2241910 by guest on 25 October 2019
E.R. Haspinger1, M. Platania1, G. Bertolini2, R. Caserini2, E. Landoni3, E. Roz4, M. C. Garassino1, N. Zilembo1, F. Agustoni1, M. Vitali1, D. Serpico1, R. Giovannetti5, F. Gelsomino1, P. Scanagatta5, L. Taveccio5, R. Gallucci1, U. Pastorino5, F.G.M. De Braud1, G. Sozzi2, L. Roz2 1 Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY 2 Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY 3 Medical Statistics, Biometry and Bioinformatics, Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY 4 Pathology Unit, Oncologic Department, Casa di Cura “La Maddalena”, Palermo, ITALY 5 Surgery Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY
Methods: We analyzed tumor samples from 60 consecutive NSCLC patients with stage IIIA-B undergoing neo-adjuvant chemotherapy with platinum-based regimens followed by radically surgery. Tumor specimen collection included pre-treatment mediastinal lymph-node biopsies (n = 23) and post-treatment surgical specimens (25 from lymph-nodes and 52 from primary tumors). CD133 status was determined by immunohistochemistry and correlations with clinico-pathological variables were evaluated using univariable and multivariable Cox models. Results: CD133 positive cells (mean 5% of total tumor cells, range 1-40%) were detected in 35% of pre-treatment samples and after chemotherapy in 38% and 32% of resected primary tumors and metastatic lymph-nodes, respectively. When both lymph nodes and primary tumor were available (24 patients) no correlation was found between CD133 status, possibly indicating different dynamics in primary tumor maintenance and dissemination. CD133 positive cells were detected more frequently in tumors with best response to chemotherapy (by ≥30% size reduction: 14/28, 50% vs. 6/ 24, 25%) suggesting enrichment of chemoresistant cells after treatment. CD133 positivity after induction chemotherapy was correlated with higher risk of local and distant recurrence (73% vs 53%), especially in patients with pre-treatment CD133+ lymph nodes (87% vs. 53%). Finally, positivity for CD133 after treatment seems to be correlated with worse overall survival (HR 2.42, 95% CI: 0.93-6.32, p = 0.184). Conclusions: Investigation of tumors after chemotherapy provides indirect evidence of chemoresistance of CD133+ cells. CD133 positive cells are correlated with worse prognosis in neo-adjuvant treatment of locally advanced NSCLC and could provide clinical relevant information for personalized therapies. Disclosure: All authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
NSCLC, locally advanced 1211P
CLINICAL RELEVANCE OF CD133 POSITIVE CELLS IN LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER
abstracts
Aim: CD133 positive cells have been identified as tumor initiating cells in non-small cell lung cancer (NSCLC) and have been shown to be resistant to conventional cytotoxic chemotherapy in experimental studies, suggesting a possible role in chemoresistance and disease relapse. However their prognostic relevance in the context of clinical treatment of NSCLC has not been fully investigated.
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv422/2241910 by guest on 25 October 2019
E.R. Haspinger1, M. Platania1, G. Bertolini2, R. Caserini2, E. Landoni3, E. Roz4, M. C. Garassino1, N. Zilembo1, F. Agustoni1, M. Vitali1, D. Serpico1, R. Giovannetti5, F. Gelsomino1, P. Scanagatta5, L. Taveccio5, R. Gallucci1, U. Pastorino5, F.G.M. De Braud1, G. Sozzi2, L. Roz2 1 Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY 2 Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY 3 Medical Statistics, Biometry and Bioinformatics, Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY 4 Pathology Unit, Oncologic Department, Casa di Cura “La Maddalena”, Palermo, ITALY 5 Surgery Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, ITALY
Methods: We analyzed tumor samples from 60 consecutive NSCLC patients with stage IIIA-B undergoing neo-adjuvant chemotherapy with platinum-based regimens followed by radically surgery. Tumor specimen collection included pre-treatment mediastinal lymph-node biopsies (n = 23) and post-treatment surgical specimens (25 from lymph-nodes and 52 from primary tumors). CD133 status was determined by immunohistochemistry and correlations with clinico-pathological variables were evaluated using univariable and multivariable Cox models. Results: CD133 positive cells (mean 5% of total tumor cells, range 1-40%) were detected in 35% of pre-treatment samples and after chemotherapy in 38% and 32% of resected primary tumors and metastatic lymph-nodes, respectively. When both lymph nodes and primary tumor were available (24 patients) no correlation was found between CD133 status, possibly indicating different dynamics in primary tumor maintenance and dissemination. CD133 positive cells were detected more frequently in tumors with best response to chemotherapy (by ≥30% size reduction: 14/28, 50% vs. 6/ 24, 25%) suggesting enrichment of chemoresistant cells after treatment. CD133 positivity after induction chemotherapy was correlated with higher risk of local and distant recurrence (73% vs 53%), especially in patients with pre-treatment CD133+ lymph nodes (87% vs. 53%). Finally, positivity for CD133 after treatment seems to be correlated with worse overall survival (HR 2.42, 95% CI: 0.93-6.32, p = 0.184). Conclusions: Investigation of tumors after chemotherapy provides indirect evidence of chemoresistance of CD133+ cells. CD133 positive cells are correlated with worse prognosis in neo-adjuvant treatment of locally advanced NSCLC and could provide clinical relevant information for personalized therapies. Disclosure: All authors have declared no conflicts of interest.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].