In pancreatic adenocarcinoma, the presence of CD4+ TILs together with CD8+ TILs serves as a good indicator of the patient's outcome after surgical treatment.

The purpose of this study was to clarify the relationship between the number of tumour-infiltrating T lymphocytes and the clinicopathological features and clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue specimens from 109 patients who underwent surgical resection for NSCLC were immunohistochemically analysed for CD4 and CD8 expression. Patients were classified into two groups according to whether their tumours exhibited a 'high' or 'low' level of CD8 þ or CD4 þ lymphocyte infiltration. Although the level of infiltration by CD8 þ T cells alone had no prognostic significance, the survival rate for patients with both 'high' CD8 þ and 'high' CD4 þ T-cell infiltration was significantly higher than that for the other groups (log-rank test, P ¼ 0.006). Multivariate analysis indicated that concomitant high CD8 þ and high CD4 þ T-cell infiltration was an independent favourable prognostic factor (P ¼ 0.0092). In conclusion, the presence of high levels of both CD8 þ T cells and CD4 þ T cells is a significant indicator of a better prognosis for patients with NSCLC, and cooperation between these cell populations may allow a significantly more potent antitumour response than either population alone.

Caveolin-1 is a major component of caveolae and plays a regulatory role in several signalling pathways. Caveolin-1 was recently identified as a metastasis-related gene in prostate cancer. The clinical effects of caveolin-1 expression in pancreatic carcinoma, however, remain unknown. In this study, we have investigated the relationship between caveolin-1 expression and the clinicopathologic variables and clinical outcome in 79 patients with pancreatic adenocarcinoma undergoing surgical resection. Caveolin-1 expression was determined by immunohistochemistry, using a polyclonal anti-caveolin-1 antibody. Patients were divided into two groups based on the extent of caveolin-1 expression: a negative expression group (immunoreactivity in less than 50% of cells) and a positive expression group. Positive caveolin-1 immunostaining was detected in 32 cases (40.5% of total), while non-neoplastic ductal epithelium showed little or no staining. Positive caveolin-1 expression was correlated with tumour diameter (P=0.0079), histopathologic grade (P=0.0272) and poor prognosis (P=0.0008). Upon multivariate analysis with Cox's proportional hazards model, positive caveolin-1 expression was shown to be an independent negative predictor for survival (P=0.0358). These results suggest that caveolin-1 overexpression is associated with tumour progression, thereby indicating a poor prognosis for certain patients undergoing surgical resection for pancreatic carcinoma.

To investigate the pathophysiological significance of infiltrating antitumour immune cells, we evaluated the quantity of immune cell intratumoral infiltration in 110 surgically resected gallbladder specimens by immunohistochemistry. We examined 45 cases of gallbladder cancer and 65 cases of benign gallbladder diseases for CD4 þ T cells, CD8 þ T cells, natural killer cells (NKCs), and dendritic cells (DCs). High levels of CD4 þ T cell, CD8 þ T cell, NKC, and DC infiltration were recognised in 51.1% (23 out of 45), 37.8% (17 out of 45), 33.3% (15 out of 45), and 48.9% (22 out of 45) of cancer specimens, respectively. High numbers of infiltrating CD4 þ and CD8 þ T cells correlated with decreasing tumour invasion, and high numbers of infiltrating DCs correlated with decreasing lymph-node tumour metastasis. Furthermore, increased infiltration of CD4 þ and CD8 þ T cells and DCs exhibited a significant correlation with prolonged survival. NKC infiltration, however, did not correlate with any of the clinicopathological factors examined. Additionally, high levels of infiltration were not identified in specimens from benign diseases, consistent with the cancerspecific activity of CD4 þ and CD8 þ T cells and DCs. In this study, we demonstrate that CD4 þ and CD8 þ tumour-infiltrating lymphocyte and DCs, but not NKCs, are important factors in the accurate prognosis of survival after surgical removal of gallbladder adenocarcinoma.

The infiltration of a cancer cell nest by CD8+ T cells is a reliable marker predicting increased survival of patients with EBDC.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion ( P = 0.0180), lymph node metastasis ( P = 0.0033), lymphatic involvement ( P = 0.0104), venous involvement ( P = 0.0224), perineural involvement ( P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification ( P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival ( P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216–132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a recently identified human tumor-associated antigen expressed on various cancer cells. It is thought that tumor cells evade immune surveillance by expression of RCAS1, which induces apoptotic cell death in receptor-positive immune cells. The purpose of our study was to investigate the relation between RCAS1 expression and the clinicopathological variables and clinical outcome in patients with pancreatic adenocarcinoma. Immunohistochemical analysis for RCAS1 was performed on paraffin-embedded specimens of 80 patients (mean age, 62 years) who underwent surgical resection for pancreatic adenocarcinoma. Of the 80 specimens, 77 (96%) were positive for RCAS1. No significant correlation was found between RCAS1 expression and age, gender, depth of invasion, tumor diameter, surgical margin, lymphatic invasion, venous invasion or histopathological grading. Borderline correlations between RCAS1 expression were noted for lymph node metastasis and stage (p ‫؍‬ 0.0608 and 0.0934, respectively). RCAS1 expression was very frequently observed and the survival of patients with high RCAS1 expression was significantly shorter than that of those with low expression (p ‫؍‬ 0.0012). Multivariate analysis using the Cox regression model indicated that high RCAS1 expression was an independent prognostic factor (risk ratio, 3.090; p ‫؍‬ 0.0090). These results suggested that RCAS1 might be a significant tumor marker for pancreatic adenocarcinoma and an unfavorable predictor for prognosis of patients who have undergone surgical resection. © 2002 Wiley-Liss, Inc. Key words: RCAS 1; tumor-associated antigen; pancreatic carcinoma; immunohistochemical analysis; prognostic factorPancreatic cancer has a very poor prognosis and is one of the most common malignancies. 1 Tumor resection is performed in 9 -36% of patients and the 5-year survival rate of patients who have undergone resection is 19 -24%. 2,3 Many attempts have been made to improve the outcome of patients' survival. Recently, significant improvements in survival have been reported compared to the survival expected from series in the 1980s. 4 -9 The mechanisms responsible for the aggressiveness of this disease are not completely understood, therefore, it is very important to find novel molecular markers that are expressed frequently and predominantly in pancreatic cancer. Furthermore, the identification of factors that significantly correlate with clinicopathological features or poor prognosis is of importance in selecting patients who would benefit from radical treatment and to understand the biological characteristics of the disease.A number of biologic markers that specifically predict the progression and prognosis of pancreatic cancer have been reported, including the K-ras oncogene, 10 -12 tumor suppressor DPC4, [13][14][15][16] and vascular endothelial growth factor (VEGF). 17 Recently, the human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) has been recognized as another ...

No abstract