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

doi:10.1016/j.prp.2019.152491

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

Tel Aviv University

Research output: Contribution to journal › Article › peer-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 language	English
Article number	152491
Journal	Pathology Research and Practice
Volume	215
Issue number	8
DOIs	https://doi.org/10.1016/j.prp.2019.152491
State	Published - Aug 2019

Keywords

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

All Science Journal Classification (ASJC) codes

Pathology and Forensic Medicine
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.prp.2019.152491

Cite this

@article{e829d0a8f9ab4f49b488eba1c3f1bc4a,

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

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.",

keywords = "Cancer stem cells, Clinicopathologic parameters, Prognosis, Renal development, Stem cell markers, Wilms{\textquoteright} tumor",

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

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier GmbH",

year = "2019",

month = aug,

doi = "10.1016/j.prp.2019.152491",

language = "الإنجليزيّة",

volume = "215",

journal = "Pathology Research and Practice",

issn = "0344-0338",

publisher = "Elsevier GmbH",

number = "8",

}

TY - JOUR

T1 - Blastemal NCAM+ALDH1+ Wilms' tumor cancer stem cells correlate with disease progression and poor clinical outcome

T2 - A pilot study

AU - Raved, Dani

AU - Tokatly-Latzer, Itay

AU - Anafi, Liat

AU - Harari-Steinberg, Orit

AU - Barshack, Iris

AU - Dekel, Benjamin

AU - Pode-Shakked, Naomi

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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.

KW - Cancer stem cells

KW - Clinicopathologic parameters

KW - Prognosis

KW - Renal development

KW - Stem cell markers

KW - Wilms’ tumor

UR - http://www.scopus.com/inward/record.url?scp=85067061643&partnerID=8YFLogxK

U2 - 10.1016/j.prp.2019.152491

DO - 10.1016/j.prp.2019.152491

M3 - مقالة

C2 - 31202518

SN - 0344-0338

VL - 215

JO - Pathology Research and Practice

JF - Pathology Research and Practice

IS - 8

M1 - 152491

ER -