Purpose: Human invariant natural killer T (NKT) cells are novel, distinct lymphocyte populations with a restricted T-cell receptor repertoire (Va24-Vh11). They play a pivotal role in immunoregulation and in antitumor activities. This study focused on Va24 + NKT cells in colorectal carcinomas and their clinicopathologic significance. Experimental Design: Va24 + NKT-cell infiltration immunohistochemistry was studied in a total of 103 colorectal carcinoma cases. The degree of NKT-cell infiltration in tumors was evaluated as low (<7 NKTcells/5 HPF) or high (z7 NKT cells/5 HPF). The correlation between the degree of infiltrated Va24 + NKTcells and clinicopathologic variables was studied statistically. Results: A small number of Va24 + NKT cells were found in the normal colorectal mucosa (2.6 F 3.7 cells/5 HPF); however, their number increased remarkably in colorectal carcinomas (15.2 F 16.3 cells/5 HPF; P = 0.0003) and a majority showed phenotype of activation. Higher NKT-cell infiltration was more frequent in women than in men (P = 0.034) and correlated with fewer lymph node metastases (P = 0.042). Patients with high NKT-cell infiltration showed higher overall (P = 0.018) as well as disease-free (P = 0.0006) survival rates. Intratumor NKT-cell infiltration was an independent prognostic factor for the overall (P = 0.033) and disease-free (P = 0.0064) survival rates. Conclusions: Increased infiltration of Va24+ NKT cells was observed in colorectal carcinomas. HigherVa24 + NKT-cell infiltration in colorectal carcinomas was an independent prognostic factor for favorable prognosis.

Summary Vascular endothelial growth factor (VEGF) may affect the phenotype of cancer cells, such as growth velocity and metastatic potential, due to its probable multifunctional property including a mitogenic activity for vascular endothelial cells. The present study was designed to investigate the association of VEGF mRNA expression with progression and metastasis of human colorectal cancer. The level of VEGF mRNA expression was quantified by Northem blot hybridization in tumorous and non-tumorous tissues obtained from 60 primary colorectal cancer patients. The ratio of the former to the latter was defined as the VEGF T/N ratio, and the prognostic significance of this ratio, following surgery, in addition to the relationship to progression and metastatic potential, was evaluated. The value of the VEGF T/N ratio was significantly correlated with the depth of tumour infiltration (P = 0.046), the incidence of liver metastasis (P < 0.0001) and lymph node metastasis (P = 0.036). Patient prognosis was estimated by the Kaplan-Meier method and the log-rank test. When the VEGF T/N ratio was higher than 4.8 for which the X2 value of the log-rank test was maximal, the tumour was defined as showing overexpression of VEGF mRNA.

CRC patients showed significant differences in the intestinal environment, including alterations of microbiota, decreased SCFAs, and elevated pH. These changes are not a result of CRC progression but are involved in CRC onset.

Objectives: Immature microvessels, which are not covered by pericytes, are irregular and leaky. We hypothesized that tumor cells can penetrate immature microvessels more easily than mature microvessels. In this study, we investigated the maturation of angiogenesis by the immunohistochemical staining of colorectal cancer specimens and determined the correlation between the microvessel count or the maturity of microvessels and clinicopathological variables. Methods: Ninety-two surgical specimens from our department were used. Double immunostaining of endothelial cells with anti-CD34 antibody and pericytes with anti-α-smooth muscle actin antibody was performed. The microvessel density (MVD) and microvessel pericyte coverage index (MPI) as an index of microvessel maturation were evaluated. Results: The MVD showed a significant positive correlation with tumor size, depth of invasion and Dukes’ stage. The MPI showed a significant positive correlation with the histological differentiation of the tumor tissues and distant metastasis at the time of operation. The high MVD group (≧26.0, n = 50) tended to have a poorer prognosis than the low MVD group (<26.0, n = 42) (p = 0.097). Next, the 50 patients in the high MVD group were classified into two subgroups of high MPI (≧78.1%, n = 25) and low MPI (<78.1%, n = 25). MPI showed a significant negative correlation with hematogenous metastasis, and the low MPI group demonstrated a significantly poorer survival than the high MPI group (p = 0.040). Conclusions: These findings demonstrate that immature neovascularization was observed in poorly differentiated tumors and was correlated with metastasis, resulting in a poorer prognosis. Taken together, not only microvessel density but also vascular maturation were crucial factors for colorectal cancer patients.

Significant changes in the intestinal environment, including marked decreases in obligate anaerobes, increases in pathogenic bacteria, and reductions in SCFAs, were detected after surgery for CRC.