Blastemal NCAM+ALDH1+ Wilms' tumor cancer stem cells correlate with disease progression and poor clinical outcome: A pilot study

Dani Raved, Itay Tokatly-Latzer, Liat Anafi, Orit Harari-Steinberg, Iris Barshack, Benjamin Dekel, Naomi Pode-Shakked

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cancer Stem Cells (CSCs) have been suggested as the culprit responsible for tumor resistance to treatment and disease recurrence. Wilms' tumor (WT) is a paradigm for studying the relation between development and tumorigenesis, showing three main histological elements: undifferentiated blastema, epithelia and stroma, mimicking human kidney development. NCAM + ALDH1+ cells were previously found to contain the cancer stem like-cell population in WT. Thus far, the correlation between histologic characterization of this cell population, clinicopathologic parameters and prognostic outcome has yet been investigated in WT. Procedures: Paraffin-imbedded primary WT specimens from twenty-four patients were immunostained for NCAM and ALDH1. Positivity and histologic compartment localization were determined by two independent observers, blinded to the clinical outcome. Clinicopathologic parameters and prognostic outcomes were determined based on the patients' medical records. The association of NCAM and ALDH1 co-localization with clinicopathologic characteristics was analyzed byχ2-test. Survival analysis was carried out by the log-rank test using Kaplan-Meier method. Results: Blastemal co-localization of NCAM and ALDH1 was observed in 33% of WTs. Metastases, ICE chemotherapy protocol, blastemal predominance following preoperative chemotherapy, recurrence and patient demise were found to significantly correlate with blastemal NCAM + ALDH1+ cell staining (p < 0.05). A significant inverse correlation between blastemal double positive cells, disease-free survival and overall survival was also observed. Conclusions: WT blastemal NCAM + ALDH1+ CSCs significantly correlate with adverse clinicopathologic parameters and poorer prognosis. These results underscore the role of CSCs in disease progression. Additionally, this pilot study supports the addition of these markers for risk stratification of WTs.

Original languageEnglish
Article number152491
JournalPathology Research and Practice
Volume215
Issue number8
DOIs
StatePublished - Aug 2019

Keywords

  • Cancer stem cells
  • Clinicopathologic parameters
  • Prognosis
  • Renal development
  • Stem cell markers
  • Wilms’ tumor

Fingerprint

Dive into the research topics of 'Blastemal NCAM+ALDH1+ Wilms' tumor cancer stem cells correlate with disease progression and poor clinical outcome: A pilot study'. Together they form a unique fingerprint.

Cite this