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Stromal expression of miR-21 in T3-4a colorectal cancer is an independent predictor of early tumor relapse.

Kang WK, Lee JK, Oh ST, Lee SH, Jung CK - BMC Gastroenterol (2015)

Bottom Line: The expression of miR-21 was investigated by in situ hybridization.Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. wonkkang@catholic.ac.kr.

ABSTRACT

Background: MicroRNA-21 (miR-21) is an oncogenic microRNA that regulates the expression of multiple cancer-related target genes. miR-21 has been associated with progression of some types of cancer. Metastasis-associated protein1 expression and loss of E-cadherin expression are correlated with cancer progression and metastasis in many cancer types. In advanced colorectal cancer, the clinical significance of miR-21 expression remains unclear. We aimed to investigate the impact of miR-21 expression in advanced colorectal cancer and its correlation with target proteins associated with colorectal cancer progression.

Methods: From 2004 to 2007, 277 consecutive patients with T3-4a colorectal cancer treated with R0 surgical resection were included. Patients with neoadjuvant therapy and distant metastasis at presentation were excluded. The expression of miR-21 was investigated by in situ hybridization. Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.

Results: High stromal expression of miR-21 was found in 76 of 277 (27.4%) colorectal cancer samples and was correlated with low E-cadherin expression (P = 0.019) and high metastasis-associated protein1 expression (P = 0.004). T3-4a colorectal cancer patients with high miR-21 expression had significantly shorter recurrence-free survival than those with low miR-21 expression. When analyzing colon and rectal cancer separately, high expression of miR-21 was an independent prognostic factor of unfavorable recurrence-free survival in T3-4a colon cancer patients (P = 0.038, HR = 2.45; 95% CI = 1.05-5.72) but not in T3-4a rectal cancer patients. In a sub-classification analysis, high miR-21 expression was associated with shorter recurrence-free survival in the stage II cancer (P = 0.001) but not in the stage III subgroup (P = 0.267).

Conclusions: Stromal miR-21 expression is related to the expression of E-cadherin and metastasis-associated protein1 in colorectal cancer. Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

No MeSH data available.


Related in: MedlinePlus

In situ hybridization for miR-21 and immunohistochemistry for E-cadherin and MTA1. (A) A representative 2 mm tumor tissue core from the colorectal cancer tissue microarray shows diffuse strong miR-21 expression in the stroma. (B) High-magnification image of insert in (A) shows that miR-21 signals are strong in the stromal cells of colorectal cancer but not in the tumor cells. Magnification x400. (C) Tumor cells show strong membranous expression of E-cadherin. Magnification x400. (D) Tumor cells show strong nuclear expression of MTA1. Magnification x400.
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Fig1: In situ hybridization for miR-21 and immunohistochemistry for E-cadherin and MTA1. (A) A representative 2 mm tumor tissue core from the colorectal cancer tissue microarray shows diffuse strong miR-21 expression in the stroma. (B) High-magnification image of insert in (A) shows that miR-21 signals are strong in the stromal cells of colorectal cancer but not in the tumor cells. Magnification x400. (C) Tumor cells show strong membranous expression of E-cadherin. Magnification x400. (D) Tumor cells show strong nuclear expression of MTA1. Magnification x400.

Mentions: miR-21 expression was found to be predominantly localized to the stroma surrounding the tumor cells (Figure 1). High levels of miR-21 were found in 76 of 277 (27.4%) CRC specimens. There was no significant correlation between high miR-21 expression and the clinicopathological features of the patients (Table 1).Figure 1


Stromal expression of miR-21 in T3-4a colorectal cancer is an independent predictor of early tumor relapse.

Kang WK, Lee JK, Oh ST, Lee SH, Jung CK - BMC Gastroenterol (2015)

In situ hybridization for miR-21 and immunohistochemistry for E-cadherin and MTA1. (A) A representative 2 mm tumor tissue core from the colorectal cancer tissue microarray shows diffuse strong miR-21 expression in the stroma. (B) High-magnification image of insert in (A) shows that miR-21 signals are strong in the stromal cells of colorectal cancer but not in the tumor cells. Magnification x400. (C) Tumor cells show strong membranous expression of E-cadherin. Magnification x400. (D) Tumor cells show strong nuclear expression of MTA1. Magnification x400.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308857&req=5

Fig1: In situ hybridization for miR-21 and immunohistochemistry for E-cadherin and MTA1. (A) A representative 2 mm tumor tissue core from the colorectal cancer tissue microarray shows diffuse strong miR-21 expression in the stroma. (B) High-magnification image of insert in (A) shows that miR-21 signals are strong in the stromal cells of colorectal cancer but not in the tumor cells. Magnification x400. (C) Tumor cells show strong membranous expression of E-cadherin. Magnification x400. (D) Tumor cells show strong nuclear expression of MTA1. Magnification x400.
Mentions: miR-21 expression was found to be predominantly localized to the stroma surrounding the tumor cells (Figure 1). High levels of miR-21 were found in 76 of 277 (27.4%) CRC specimens. There was no significant correlation between high miR-21 expression and the clinicopathological features of the patients (Table 1).Figure 1

Bottom Line: The expression of miR-21 was investigated by in situ hybridization.Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. wonkkang@catholic.ac.kr.

ABSTRACT

Background: MicroRNA-21 (miR-21) is an oncogenic microRNA that regulates the expression of multiple cancer-related target genes. miR-21 has been associated with progression of some types of cancer. Metastasis-associated protein1 expression and loss of E-cadherin expression are correlated with cancer progression and metastasis in many cancer types. In advanced colorectal cancer, the clinical significance of miR-21 expression remains unclear. We aimed to investigate the impact of miR-21 expression in advanced colorectal cancer and its correlation with target proteins associated with colorectal cancer progression.

Methods: From 2004 to 2007, 277 consecutive patients with T3-4a colorectal cancer treated with R0 surgical resection were included. Patients with neoadjuvant therapy and distant metastasis at presentation were excluded. The expression of miR-21 was investigated by in situ hybridization. Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.

Results: High stromal expression of miR-21 was found in 76 of 277 (27.4%) colorectal cancer samples and was correlated with low E-cadherin expression (P = 0.019) and high metastasis-associated protein1 expression (P = 0.004). T3-4a colorectal cancer patients with high miR-21 expression had significantly shorter recurrence-free survival than those with low miR-21 expression. When analyzing colon and rectal cancer separately, high expression of miR-21 was an independent prognostic factor of unfavorable recurrence-free survival in T3-4a colon cancer patients (P = 0.038, HR = 2.45; 95% CI = 1.05-5.72) but not in T3-4a rectal cancer patients. In a sub-classification analysis, high miR-21 expression was associated with shorter recurrence-free survival in the stage II cancer (P = 0.001) but not in the stage III subgroup (P = 0.267).

Conclusions: Stromal miR-21 expression is related to the expression of E-cadherin and metastasis-associated protein1 in colorectal cancer. Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

No MeSH data available.


Related in: MedlinePlus