Prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in colorectal cancer.

The purpose of this study was to evaluate the prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in patients with colorectal cancer. A total of 97 adenocarcinomas of the colon and rectum were examined. Immunohistochemical staining was performed by the standard avidin-biotin-peroxidase complex method using antibodies to CD8 and CD68. Peritumoral infiltration by CD8+ T cells or macrophages was evaluated along the invasive margin of the cancer in each specimen. The area with the most abundant infiltration was selected, and the number of immunoreactive positive cells counted at x400 magnification. Patients were divided into two groups based on the degree of infiltration by each cell type: namely those with a high level of infiltration (more than the mean number of positive cells) and those with a low level of infiltration (less than the mean number of positive cells). Patients with a low level of macrophage infiltration had a significantly deeper depth of invasion than patients with a high level of macrophage infiltration (P=0.027). The percentage of patients with a high level of macrophage infiltration was significantly higher in vascular invasion-negative cases (46.7%) than in vascular invasion-positive cases (22.7%; P=0.045), and in lymph node metastasis-negative cases (52.9%) than in lymph node metastasis-positive cases (28.3%; P=0.014). Overall survival was significantly shorter for patients with a low level of CD8+ T cell infiltration than those with a high level of CD8+ T cell infiltration (P=0.01). The survival rate for patients with a high level of both CD8+ T cell and macrophage infiltration was 100%. In conclusion, both CD8+ T cell and macrophage peritumoral infiltration indicates anti-tumoral action in patients with colorectal cancer.

Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma.

The protein p27/kip1 is a cyclin-dependent kinase inhibitor that regulates cell-cycle progression. In the present study, p27/kip1 expression as well as tumor cell proliferation and apoptosis were investigated in 80 colorectal carcinomas, using anti-p27/kip1 antibodies, in situ apoptosis detection kits and anti-PCNA antibodies. Immunohistochemical staining indicated that p27/kip1 was localized heterogeneously in the nuclei of cancer cells. The frequency of samples positive for p27/kip1 was 53.8% (43/80). There was no significant correlation between p27/kip1 status and clinicopathologic factors. Mean apoptotic index (AI) in p27/kip1-positive patients (3.22+/-1.65) was significantly higher than in p27/kip1-negative patients (2.46+/-1.44; p=0.033). No correlation was observed between p27/kip1 expression and the PCNA labeling index (PCNA-LI) (p=0.47). Overall survival was significantly longer for patients who were p27/kip1-positive (80.7%) compared to those who were negative (49.3%; p=0.0003). Univariate analysis revealed no significant differences between prognosis and AI or PCNA-LI. In multivariate analysis, p27/kip1 expression was found to be an independent prognostic marker (p=0.015). In conclusion, the present study shows that p27/kip1 is a potentially important prognostic and predictive marker for outcome in colorectal carcinoma. These results might be explained by the role of p27/kip1 in promoting apoptosis.

[A case of multiple lung metastases of colon cancer with long-term survival following 5'-DFUR and cimetidine therapy].

A 77-year-old woman treated for diabetes mellitus was admitted to our hospital for further examination of abnormal findings on chest plain radiograph. Many nodular shadows in both lung fields were seen on chest X ray and chest CT scan. Colonoscopic examination revealed a type 2 tumor in the ascending colon. We diagnosed this case as ascending colon carcinoma with multiple lung metastases, and performed right hemicolectomy and D1 lymph node dissection. After surgery, the patient was administered 5'-DFUR 600 mg/body/day, cimetidine 800 mg/body/day orally. Though no remarkable reduction of tumors was recognized, the increase of tumor size was relatively slow. The patient remains alive 3 years after surgery.

[A case of colon cancer with liver metastases and lymph node metastases successfully treated with surgery followed by CPT-11 and 5-FU chemotherapy].

A sixty-year-old woman underwent right hemicolectomy and D2 lymph node dissection. However, a solitary liver metastasis and para-aortic lymph node metastasis were detected three months after surgery. Chemotherapy using CPT-11 and 5-FU (civ) was immediately performed. After one course of this regimen, the chemotherapeutic effect was evaluated as a partial response (PR) in the liver metastasis, and as a complete response (CR) in the para-aortic lymph node. There was a massive therapeutic effect without side effects. Two further courses of chemotherapy were performed after changing from 5-FU to 5'-DFUR. Both regions of metastasis (liver and lymph nodes) continue to exhibit CR and the patient is free from any symptoms almost one year after surgery. The authors believe that this regimen is very effective and will contribute quality of life in advanced colon cancer patients.

Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma.

BACKGROUND: It has been reported that p53 regulates the G2-M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The objective of the current study was to clarify the role of the cell cycle regulators, cyclin B1 and p53, in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Tissue samples from 71 patients with ESCC were included in the current study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemistry. RESULTS: Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 20% of tumor cells were cyclin B1 positive in 38 patients (49.3%). Several clinicopathologic parameters, including macroscopic configuration (P < 0.01), pathologic tumor status (P < 0.05), pathologic lymph node status (P < 0.001), pathologic metastatic status (P < 0.01), tumor stage (P < 0.0001), and invasion of lymphatic vessels (P < 0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also were correlated with a poor prognosis in patients with ESCC in univariate analysis (P < 0.0001) and multivariate analysis (P = 0.0135). In contrast, p53 expression exhibited no significant correlation with the level of cyclin B1 expression and was not associated with prognostic parameters in patients with ESCC. CONCLUSIONS: These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC.