Immunohistochemical Detection of Cancer Stem Cell Related Markers CD44 and CD133 in Metastatic Colorectal Cancer Patients

Abstract

Aim. The goal of this study was to semiquantitatively detect presence of cancer stem cells markers CD44 and CD133 in immunohistochemically stained paired samples of colorectal cancer (CRC) and colorectal liver metastases (CLM). Level of staining intensity was compared to clinical and pathological characteristics of tumors with the aim to identify impact of CD44 or CD133 expression on tumor behavior. Patients and Methods. Formalin fixed paraffin embedded samples from 94 patients with colorectal tumor and liver metastases were collected at Sikl's Department of Pathology. Samples were stained by antibodies against CD44 and CD133. Presence and intensity of staining was assessed semiquantitatively by three trained researchers. Results. Patients with higher level of CD133 staining in CRC had longer disease free interval (Cox-Mantel P = 0.0244), whereas we found no relation between CD44 expression and overall survival or disease free interval. CD133 expression in CRC and CLM differed based on CRC grading; in case of CD44 we found differences in staining intensity in individual stages of tumor lymph node invasion. Conclusion. Effect of cancer stem cell markers on prognosis of colorectal cancer can vary depending on pathological classification of tumor, and we have shown that CD133, generally considered to be a negative marker, can bear also clinically positive prognostic information in group of patients with colorectal liver metastases.

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases

“…This is in accordance with the results found by Narita et al, who compared patients with early recurrence after liver resection with those with late recurrence, and found increased CD133 expression within the first group (27). In the present study, no relation between CD133 expression and OS was found, corresponding to the findings by Pitule et al However, Pitule et al neither found CD133 expression in liver metastases to be related to DFS (17), which contradicts the current results. Other contradicting results were reported by Yamamoto et al who found CD133 expression in liver metastases to be associated with a better OS after hepatectomy (16) and Kishikawa et al who reported both a better OS and DFS (18).…”

“…In the present study, CD44 expression did not predict OS or DFS, a finding supported by two other reports on CSC markers in liver metastases (16,17). Neither did we find CD24 expression to be of significance, but this has not been tested in the same manner previously.…”

“…Only a limited number of studies have previously analysed the expression of CSC markers in colonic liver metastases and how this predicts long-term outcome (16)(17)(18)27). These reports mainly considered CD133 and CD44, whilst the current study, to our knowledge, is the first to analyse all three markers, including CD24, in colonic liver metastases and to assess their prognostic significance for outcome after hepatectomy.…”

“…In colorectal cancer patients, CD44 and CD24 have been associated with decreased OS (13, 14), whilst a metaanalysis showed that CD133 is correlated with a worsened OS and DFS (15). Studies regarding the expression of these markers in colonic liver metastases and its influence on survival after hepatectomy are sparse (16)(17)(18). The aim of this study was to assess the expression of CD44, CD133 and CD24 in colon cancer liver metastases and to analyse their predictive value for OS and DFS after liver resection.…”

Cancer stem cells in human digestive tract malignancies

“…In addition, it was demonstrated that CD44 + CD133 - [169] and EpCAM + CD133 - [170] CRC cells possessed features of CSCs including self-renewal, invasion, and tumorigenicity. Analyzing patient samples added more discrepancies to the concept that CRC-SCs could be recognized by a universal marker; despite several reports introducing CD133 as a prognostic factor for disease survival and tumor stage, differentiation, recurrence, and invasion in CRC [171][172][173][174][175][176][177][178], other studies indicated a positive correlation [179] or no association [180] between CD133 expression and clinicopathological features.…”