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Immunohistochemical detection of cancer stem cell related markers CD44 and CD133 in metastatic colorectal cancer patients.

Pitule P, Cedikova M, Daum O, Vojtisek J, Vycital O, Hosek P, Treska V, Hes O, Kralickova M, Liska V - Biomed Res Int (2014)

Bottom Line: Samples were stained by antibodies against CD44 and CD133.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.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Husova 3, 306 05 Pilsen, Czech Republic ; Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague, Karlovarská 48, 301 00 Pilsen, Czech Republic.

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.

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Kaplan-Meier curves comparing the levels of CD44 (a) or CD133 (b) staining intensity in primary colorectal cancer sample to the disease free interval.
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fig3: Kaplan-Meier curves comparing the levels of CD44 (a) or CD133 (b) staining intensity in primary colorectal cancer sample to the disease free interval.

Mentions: We did not find any statistically significant effect of CD44 expression in CRC or CLM on either OS or DFI (Figure 3(a)). CD133 positivity over median in primary tumor was found to be a positive prognostic factor of DFI (Cox-Mantel P = 0.0244) (Figure 3(b)). This finding was confirmed by Cox proportional hazards model using the CD133 CRC score as a single independent variable (Chi-square P = 0.0137). CD133 positivity in CLM was not connected to any effect on OS or DFI (Cox-Mantel P = 0.3855). We identified differences in markers quantity based on grading, where CD133 in CRC was present in lower amount in G1 compared to G2 (Mann-Whitney U Test P = 0.0248) and CD133 in CLM had lower expression in G1 compared to combined G2 and G3 stage (Mann-Whitney U Test P = 0.0470) (Figures 4(a) and 4(b)). Comparison of studied markers with TNM classification revealed differences in CD44 in CRC depending on lymph node invasion—higher expression of CD44 was detected in N0 stage compared to combined N1 and N2 groups (Mann-Whitney U Test P = 0.0287) as well as N0 compared to N2 (Mann-Whitney U Test P = 0.0212) (Figures 4(c) and 4(d)).


Immunohistochemical detection of cancer stem cell related markers CD44 and CD133 in metastatic colorectal cancer patients.

Pitule P, Cedikova M, Daum O, Vojtisek J, Vycital O, Hosek P, Treska V, Hes O, Kralickova M, Liska V - Biomed Res Int (2014)

Kaplan-Meier curves comparing the levels of CD44 (a) or CD133 (b) staining intensity in primary colorectal cancer sample to the disease free interval.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016925&req=5

fig3: Kaplan-Meier curves comparing the levels of CD44 (a) or CD133 (b) staining intensity in primary colorectal cancer sample to the disease free interval.
Mentions: We did not find any statistically significant effect of CD44 expression in CRC or CLM on either OS or DFI (Figure 3(a)). CD133 positivity over median in primary tumor was found to be a positive prognostic factor of DFI (Cox-Mantel P = 0.0244) (Figure 3(b)). This finding was confirmed by Cox proportional hazards model using the CD133 CRC score as a single independent variable (Chi-square P = 0.0137). CD133 positivity in CLM was not connected to any effect on OS or DFI (Cox-Mantel P = 0.3855). We identified differences in markers quantity based on grading, where CD133 in CRC was present in lower amount in G1 compared to G2 (Mann-Whitney U Test P = 0.0248) and CD133 in CLM had lower expression in G1 compared to combined G2 and G3 stage (Mann-Whitney U Test P = 0.0470) (Figures 4(a) and 4(b)). Comparison of studied markers with TNM classification revealed differences in CD44 in CRC depending on lymph node invasion—higher expression of CD44 was detected in N0 stage compared to combined N1 and N2 groups (Mann-Whitney U Test P = 0.0287) as well as N0 compared to N2 (Mann-Whitney U Test P = 0.0212) (Figures 4(c) and 4(d)).

Bottom Line: Samples were stained by antibodies against CD44 and CD133.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.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Husova 3, 306 05 Pilsen, Czech Republic ; Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague, Karlovarská 48, 301 00 Pilsen, Czech Republic.

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.

Show MeSH
Related in: MedlinePlus