Perineural Invasion Is a Prognostic Factor and Treatment Indicator in Patients with Rectal Cancer Undergoing Curative Surgery: 2000-2011 Data from a Single-center Study.

BACKGROUND/AIM: The aim of the present study was to investigate whether perineural invasion (PNI) was a prognostic index for patients who underwent curative surgery for Dukes' grade B and C rectal cancer. PATIENTS AND METHODS: A total of 645 patients with rectal cancer between January 2000 and December 2011; 363 with Dukes' B or C stages who did not undergo chemoradiotherapy were reviewed. RESULTS: Of 363 patients, 83 (22.9%) were PNI-positive. The 5-year overall survival and disease-specific survival rates were significantly worse for patients with PNI-positive Dukes' B or C disease compared to those with PNI-negative disease. There was no significant difference in the recurrence pattern (hematogenous or lymphatic spread), but patients with PNI-positive disease had a significantly higher rate of recurrence compared to those with PNI-negative disease (p<0.001). CONCLUSION: PNI was a significant prognostic factor in rectal cancer, and the PNI status in primary rectal cancer pathology specimens should be considered for therapy stratification.

Nuclear Y-Box-binding Protein-1 Expression Predicts Poor Clinical Outcome in Stage III Colorectal Cancer.

BACKGROUND/AIM: Y-Box-binding protein-1 (YB-1), a DNA/RNA-binding protein, is an important oncogenic transcription and translation factor. We aimed to evaluate the relationships between nuclear YB-1 expression, epidermal growth factor receptor (EGFR) status, and poor clinical outcomes in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Nuclear YB-1 expression was immunohistochemically analyzed in CRC tissues obtained from 124 patients who underwent curative resection between 2005 and 2008. Correlations between nuclear YB-1 expression, various clinicopathological characteristics, EGFR status, and prognostic factors were evaluated. RESULTS: High-grade nuclear YB-1 expression was detected in 62.9% of cases and was found to be an independent predictor of poorer overall survival (p<0.001) and relapse-free survival (p<0.001). A trend was also observed towards a positive correlation between nuclear YB-1 expression and EGFR status (p=0.051). CONCLUSION: Nuclear YB-1 expression is a useful prognostic biomarker that correlates with EGFR status in patients with CRC.

A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells).

BACKGROUND: Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis. METHODS: The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed. RESULTS: A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45). CONCLUSIONS: This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.

Analysis of Wnt and ß-catenin Expression in Advanced Colorectal Cancer.

BACKGROUND: Wnt/ß-catenin signaling plays an important role in colorectal cancer (CRC). Wnt has many sub-types and it is uncertain which of them affect progression of CRC. PATIENTS AND METHODS: We analysed 201 patients who underwent curative surgery for CRC. We investigated the relationship between the expression of Wnt and ß-catenin proteins and prognosis using immunohistochemistry. RESULTS: The high expression of Wnt1 correlated with high expression of nuclear and cytoplasmic ß-catenin (p=0.0004, p=0.02). The high expression of Wnt5a also correlated with high expression of membrane ß-catenin (p=0.03). In multivariate analysis, lymph node metastasis (p=0.046) and high expression of nuclear ß-catenin (p=0.04) were independent prognostic factors for survival. CONCLUSION: The expression of nuclear ß-catenin is a useful predictive marker in CRC. It is suggested that Wnt1 may be the main activator of the ß-catenin signaling pathway and that Wnt5a may stabilize adherens junctions, thereby suppressing the epithelial-mesenchymal transition.