Microsatellite instability (MSI) is observed in 13-44% of gastric carcinoma. The etiology of MSI in gastric carcinoma has not been clearly defined. To assess the role of mismatch repair in the development of MSI in gastric cancer , expression of hMSH2 and hMLH1 was explored. We examined 117 gastric carcinomas for MSI and observed instability at one or more loci in 19 (16%) of these tumors. Of the 19 tumors with MSI, nine exhibited low-rate MSI (MSI-L) with instability at <17% of loci , whereas the remaining 10 exhibited Microsatellite instability (MSI) is a form of genetic instability observed in virtually all tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and in a subset of various sporadic tumors, including colorectal, gastric and endometrial cancer.1-17 The majority of HNPCC patients have germline mutations of one of several DNA mismatch repair (MMR) genes, most frequently hMSH2 or hMLH1.18 -21 Somatic mutations, which inactivate the remaining wild-type allele, lead to defective MMR and a form of genomic instability known as microsatellite instability. Defective MMR is thought to promote tumorigenesis by accelerating the accumulation of mutations in oncogenes and tumor suppressor genes. [22][23][24] MSI has been observed in a subset of gastric carcinomas ranging from 13% to 44%, depending on the group of cases studied and the type and number of markers examined.5,25 Interestingly, mutations of hMSH2 and hMLH1, germline or somatic, are infrequent in sporadic tumors with MSI, including gastric carcinoma.26,27 Studies of MSIϩ sporadic colorectal cancer observed a frequent absence of hMLH1 expression, despite the lack of identifiable germline or somatic mutations of the hMLH1 gene. 28,29 More recent studies have shown that hypermethylation of the hMLH1 promoter rather than inactivating germline/somatic mutations appear to underlie the loss of hMLH1 expression. 30,31 In this study, immunohistochemical stains for hMLH1 and hMSH2 were performed on gastric carcinoma with high-level (MSI-H), low-level (MSI-L), or no MSI (MSS). Our results shed further light on the origin of high-level MSI in gastric carcinoma. Materials and Methods Sample Collection and ProcessingOne hundred seventeen surgically resected primary gastric adenocarcinoma specimens were collected and stored at Ϫ80°C over the past decade from hospitals in the United States and the Tuscany region of Italy. Normal tissue or peripheral blood samples were obtained from these patients as well. Sample collections were performed according to internal review board-approved protocols. Tumor, node, metastasis (TNM) staging of resected cancers was assessed according to the consen-

A case-control study involving interviews with 1,016 gastric cancer (GC) patients and 1,159 population-based controls in high- and low-risk areas was conducted to evaluate dietary factors and their contribution to the marked geographic variation in mortality from this cancer within Italy. Risks of GC were found to vary significantly with estimated nutrient intake. Risk rose with increasing consumption of nitrites and protein, and decreased in proportion to intake of ascorbic acid, beta-carotene, alpha-tocopherol, and vegetable fat. The associations with nitrite and beta-carotene tended to fade, however, in multivariate analyses adjusting for intake of other nutrients. Ascorbic acid showed the strongest geographic gradient, with highest consumption in low-risk areas. The findings suggest that the protective effects we previously reported for consumption of fresh fruit, fresh vegetables and olive oil may be linked to the vitamins C and E contained in these foods. The findings are consistent with the hypothesis that N-nitroso compounds are involved in GC risks, since elevated risks were apparent for agents (nitrites, protein) that promote nitrosation, while decreased risks were found for nutrients (ascorbic acid and alpha-tocopherol) which inhibit the process.

The Epstein-Barr Virus (EBV) has been implicated in the pathogenesis of Hodgkin's disease (HD). However, the association of EBV with this disease varies greatly from series to series and from country to country. Epidemiological studies have shown differences in HD occurring in different parts of the world. In particular, it has been reported that HD in developing countries differs from HD in Western countries in terms of epidemiological, pathological and clinical characteristics. These discrepancies among populations suggest an interaction with environmental factors and a direct role of different etiological agents. At present, there are no data on the frequency of association of EBV with HD in equatorial Africa. In this study, a large series of HD cases have been collected at the University of Nairobi, Kenya, and at the Universities of Bologna and Siena, Italy. The cases have been reviewed and classified according to the REAL Classification and the presence of EBV has been assessed by in situ hybridization (ISH). A statistical difference in EBV expression was found between HD from Kenya and HD from Italy. EBV-positive neoplastic cells were detected in 92% of Kenyan cases, whereas only 48% of Italian cases showed EBER1/2 positivity in the neoplastic cells. Our results suggest that, in Kenya, EBV plays a more direct role in the pathogenesis of HD, as it does for endemic Burkitt lymphoma.

Cell loss, perhaps as important as cell production in determining the size of an expanding cell population, has not usually been registered in quantitative cellular kinetic analyses of neoplastic disorders. The present retrospective study on various types and subtypes of non-Hodgkin's lymphomas (NHLs; n = 170) was designed to test the usefulness of a novel additional parameter, the 'turnover index' (TI), which is the sum per case of the mitotic index and the apoptotic index. Results document that TIs clearly distinguished between categories and subtypes of NHLs according to the Kiel classification. Cluster analysis of TIs plotted against the percentage of Ki-67-positive cells per case revealed that about one-third of the high-grade malignancy lymphomas actually belonged to the low-turnover lymphomas. Overall survival was longer in the low- than in the high-turnover group of lymphomas. Assessment of TIs can, for practical diagnostic purposes, be replaced by counting mitotic figures and apoptotic cells in several high-power fields. The TI concept may help to interpret the kinetics of NHLs in terms of accumulation vs. proliferation of cells.

The most interesting sources of information about the pathogenesis of posterior capsular opacification seem to be histopathological studies and in vitro tissue cultures. Since our surgical technique is extracapsular cataract extraction, the explants we used for tissue culture consisted of the anterior capsule epithelial sheet without the equatorial germinative zone. We successfully overcame several problems by using the autologous plasma clot culture method. This medium, considered the optimal one for this type of culture, allowed us to study the heterogeneous behavior of the epithelial cells in culture. Using the plasma clot culture method, we were able to demonstrate in vitro fibroblastic transformation of the epithelial cells. Histopathological findings of particular cases of posterior capsule opacification and immunohistochemistry of the human lens are also reported.