Abstract

Objective. Stage I colorectal carcinomas display a highly variable behavior which is not accurately predicted by the available prognostic markers. CD133 is considered a useful marker to identify the so-called cancer stem cells in colorectal cancers (CRCs) and its expression has been shown to have prognostic significance in CRC patients. This study aimed to verify whether immunohistochemical evaluation of CD133 might correlate with the progression risk of stage I CRC patients. Material and methods. Expression levels of the CD133 molecule were analyzed and compared in two series of stage I surgically resected CRC patients showing disease progression and death for the disease and patients with no evidence of disease progression after at least 6 years after surgery. Results. A positive staining for CD133 was detected in 52% of the cases with poor prognosis and only in 9% of the group with good prognosis, and this difference was highly significant (p < 0.001). A significant correlation was detected between CD133 expression and histological parameters, such as tumor budding, vascular invasion, and presence of lymph node micrometastases but not tumor grading, gender, and age. Disease-free survival and cancer-specific survival of CD133 negative tumors were significantly longer compared to positive cases. In multivariate analyses, CD133 staining confirmed to be a predictor of shorter survival independent from vascular invasion but not from lymph nodes micrometastases. Conclusions. These findings demonstrate that CD133 immunostaining is a useful predictor of high risk progression in stage I CRC patients and might help to identify patients eligible for adjuvant chemotherapy.

Highlights

  • CD133, known as prominin-1, a transmembrane pentaspan molecule, is considered a putative stem cell marker expressed in several normal and cancer tissues [1]

  • The same population of patients were previously characterized [13] in detail and reported to display vascular invasion in four (5.7%) controls and 13 (52%) cases (p < 0.001) and cytokeratin-positive micrometastasis in one (1.4%) control and in 18 of 25 (72%) stage I colorectal cancers (CRCs) patients who died of the disease (p < 0.001) [13]

  • A small fraction of stage I patients die of recurrence or metastases and available prognostic factors do not allow the identification of high risk patients [12]

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Summary

Introduction

CD133, known as prominin-1, a transmembrane pentaspan molecule, is considered a putative stem cell marker expressed in several normal and cancer tissues [1]. The exact role(s) of the molecule in human colorectal cancer (CRC) tumorigenesis remain unknown [5,6], CD133 is presently considered a useful marker to identify cancer stem cells (CSC) in CRCs and its expression level has been shown to have prognostic significance in colon cancer patients [7,8,9,10,11]. A small subset of stage I CRC patients display relapses and disease progression and available prognostic markers are not able to identify this subgroup of patients which might benefit from a more aggressive (i.e., adjuvant therapies) treatment [12]. The potential prognostic significance of CD133 was evaluated on the overall population of stage I patients included in the study

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