The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.

Criteria for the staging and grading of neuroendocrine tumors (NETs) of midgut and hindgut origin were established at the second Consensus Conference in Frascati (Rome) organized by the European Neuroendocrine Tumor Society (ENETS). The proposed tumor-node-metastasis (TNM) classifications are based on the recently published ENETS Guidelines for the Diagnosis and Treatment of gastroenteropancreatic NETs and follow our previous proposal for foregut tumors. The new TNM classifications for NETs of the ileum, appendix, colon, and rectum, and the grading system were designed, discussed, and consensually approved by all conference participants. These proposals need to be validated and are meant to help clinicians in the stratification, treatment and follow-up of patients.

There is increasing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumours. The aim of the present study was to examine the relationship between tumour T-lymphocyte subset infiltration, the systemic inflammatory response and cancer-specific survival in patients with colorectal cancer. In all, 147 patients undergoing potentially curative resection for colorectal cancer were studied. Circulating concentrations of C-reactive protein were measured prior to surgery. CD4 þ and CD8 þ T-lymphocyte infiltration of the tumour was assessed using immunohistochemistry and a point counting technique. When patients were grouped according to the percentage tumour volume of CD4 þ T-lymphocytes, there was no difference in terms of age, sex, tumour site, stage and tumour characteristics. However, there was an inverse relationship between percentage tumour CD4 þ T-lymphocytes and C-reactive protein (Po0.01). On univariate analysis, both C-reactive protein concentrations (Po0.001) and percentage tumour volume of CD4 þ (Po0.05) T-lymphocytes were associated with cancer-specific survival. The results of the present study show that low tumour CD4 þ T-lymphocyte infiltration is associated with elevated C-reactive protein concentrations and both predict poor cancer-specific survival.

The present study examined the relationship between tumour stage, grade, T-lymphocyte subset infiltration and survival in patients who had undergone potentially curative surgery for renal clear-cell cancer (n ¼ 73). Intratumoural CD4 þ T-lymphocyte infiltrate was associated with poor cancer-specific survival, independent of grade, in this cohort. British Journal of Cancer (2003Cancer ( ) 89, 1906Cancer ( -1908 Local and systemic inflammatory responses are regulated through the production of proteins, such as cytokines, by immunologically active cells. In cancer, this mechanism is disturbed by the presence of the tumour and this dysregulation may contribute to the poorer outcome in the cancer patient (Balkwill and Mantovani, 2001).Recent work has suggested that the presence of specific Tlymphocyte subsets has prognostic value in a number of solid tumours. Naito et al (1998) demonstrated that increased numbers of CD8 þ T lymphocytes in the tumour were associated with better survival in patients with colorectal cancer.There has been little work carried out in renal cancer and the results appear to be different from other solid tumours. Kolbeck et al (1992) in a small study reported that increased tumour T-cell infiltration was associated with increased tumour recurrence. More recently, in a larger series, it has been reported that increased numbers of CD8 þ T lymphocytes in the tumour are associated with poor survival in patients with renal cancer (Nakano et al, 2001).The aim of the present study was to examine the relationship between tumour stage, grade, T-lymphocyte subset infiltration and survival in patients who had undergone potentially curative surgery for renal clear-cell cancer. PATIENTS AND METHODS PatientsPatients with histologically proven renal clear-cell cancer that, on the basis of preoperative CT-scan of the abdomen and chest and pathological assessment of the resected tumour, were considered to have undergone potentially curative surgery between July 1997 and December 2000 in the North Glasgow NHS Trust were included in the study. Pathological staging was based on TNM and classified as pII or 4II (Guinan et al, 1997).The study was approved by the local ethical committee. ImmunohistochemistryBlocks from the primary tumour were fixed in 10% buffered formalin and embedded in paraffin wax. One representative block of tumour was selected for each patient. Sections (4 mm) were cut and mounted on slides coated with aminopropyltriethoxysilane. Sections were then immunostained using the peroxidase-based Envision (Dako, Cambridgeshire, UK) technique. The primary antibody for CD4 was mouse monoclonal (Vector, Peterborough, UK) and that for CD8 was mouse monoclonal (Dako, Cambridgeshire, UK). Sections were dewaxed and rehydrated. Endogenous peroxidase was blocked by incubation in 0.3% hydrogen peroxide for 10 min. Antigen retrieval for CD8 was performed by microwaving in 1 mM EDTA buffer, pH 8, for 5 min at full pressure in aplastic pressure cooker in a microwave oven. Antigen retrieval for CD4 was achieved b...

Overexpression of HER2 is detected immunohistochemically in a proportion of epithelial neoplasms of diverse histogenesis in addition to ductal breast cancer. The standardized format of the assay will allow comparative analyses of studies performed at different institutions.