NCAM+ALDH1+ Wilms` Tumor Cancer Stem Cells Correlate with Progressive Disease and Tumor Recurrence – A Pilot Study

Dani Raved 1 Naomi Pode-Shaked 1,3 Benjamin Dekel 1,3 Iris Barshack 2,3
1Safra Children's Hospital, 1Pediatric Stem Cell Research Institute, Safra Children's Hospital, Sheba Medical Center
2Pathology, Institute of Pathology, Sheba Medical Center
3Tel Aviv University, Sackler School of Medicine, Tel Aviv University

Introduction: We have previously found that NCAM+ALDH1+ cells contain the cancer stem like-cell population in Wilms` tumor. Thus far, the correlation between the histologic qualitative and quantitative characterization of this cell population and prognostic outcomes has yet to be investigated in Wilms`tumor.

Study objective: We examined the association between NCAM+ALDH1+ WT-CSC quantity and localization in WT specimens, and several clinical adverse outcomes.

Methods: Paraffin imbedded primary Wilms` tumor specimens from 20 patients were immuno-stained for NCAM and ALDH1. Intensity and positivity were determined by a pathologist, blinded to the clinical outcome. Clinical parameters and prognostic outcomes were determined based on the patients` medical records. The correlation between the histologic features and clinical parameters was assessed.

Results: Tumor recurrence was observed in 4 of the cases. Neo-adjuvant chemotherapy was used in 4 of the cases. The highest amount of double positive (NCAM1+ALDHA1+) cells was detected in both of these subgroups (5-25%). Over 50% double positive cells were detected in one case in whom following treatment with neo-adjuvant chemotherapy the tumor had recurred and consequently the patient succumbed to his illness. Additionally, the percentage of NCAM1+ALDH1+ cells was highest in the blastemal component of the tumors.

Conclusions: Quantity and specific localization of NCAM/ALDH1 positive cancer stem cells in Wilms-tumor correlates with treatment protocols that include neo-adjuvant chemotherapy and with tumor relapse. These results underscore the role of CSCs in disease progression. Additionally, localization of the NCAM1+ALDH1+ cells to Wilms` tumor blastema corresponds to our previous findings of the malignant nature of these Wilms` tumor blastemal CSCs

Dani Raved
Dani Raved








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