1211P - Clinical relevance of CD133 positive cells in locally advanced non-small cell lung cancer

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Translational Research
Presenter Eva Haspinger
Citation Annals of Oncology (2014) 25 (suppl_4): iv417-iv425. 10.1093/annonc/mdu348
Authors E.R. Haspinger1, M. Platania1, G. Bertolini2, R. Caserini2, E. Landoni3, E. Roz4, M. 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
  • 1Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Department Of Experimental Oncology And Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 33medical Statistics, Biometry And Bioinformatics, Unit Of Clinical Epidemiology And Trial Organization, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 4Pathology Unit, Oncologic Department, Casa di Cura “La Maddalena”, PALERMO/IT
  • 5Surgery Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT

Abstract

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.

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.