Normal gastric mucosa expresses MUC1 and MUC5AC in foveolar epithelium and MUC6 in mucous neck cells of the body and deep glands of the antrum. Several studies have reported aberrant expression of an under-glycosylated form of MUC1, decreased expression of "gastric" mucins and aberrant expression of "non-gastric" mucins in gastric carcinoma. In this study, we analysed the expression profile of mucins MUC1, MUC2, MUC5AC and MUC6 in 94 gastric carcinomas using immunohistochemistry. Our results showed that: (1) mucin expression is associated with tumour type (MUC5AC with diffuse and infiltrative carcinomas and MUC2 with mucinous carcinomas) but not with the clinico-biological behaviour of the tumours; and (2) mucin expression is associated with tumour location (MUC5AC with antrum carcinomas and MUC2 with cardia carcinomas), indirectly reflecting differences in tumour differentiation according to tumour location.

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours of the digestive tract and are commonly driven by oncogenic mutations in KIT and PDGFRA genes. Tumour size, location, mitotic index and KIT/PDGFRA mutations are the most important prognostic parameters in GISTs. However, additional studies screening for new molecular prognostic markers in GISTs are missing. Raf kinase inhibitor protein (RKIP) has been considered as a suppressor of metastasis and a prognostic marker in several neoplasms. In the present study we aimed to examine whether RKIP expression is associated with GIST clinical-pathological features. Using immunohistochemistry, we determined RKIP expression levels in a well-characterised series of 70 GISTs. We found that RKIP is expressed in the great majority of cases, and absent in approximately 9% of GISTs. Additionally, we found that loss of RKIP expression was not due to the promoter methylation as assessed by methylation-specific PCR. Loss of RKIP expression was associated with poor disease-specific survival and with tumour necrosis in GISTs. Furthermore, a statistical tendency was observed between the positive RKIP expression and absence of metastasis. So far, this is the first study assessing RKIP expression levels in GISTs. We conclude that loss of RKIP expression could have an important role as prognostic marker in GISTs.

Based on the results of this study, the authors recommend that diverticulitis management should be based on the severity of the disease and not on the age of the patient.

Background/Aims: The putative influence of tumor location on the biologic behavior of gastric carcinomas remains controversial. The aim of this study was to investigate if carcinomas arising in the three types of gastric mucosa (cardia, fundus/body and antrum) have different clinical and pathologic profiles and carry a different prognosis. Methods: Three hundred and two patients with cardia or gastric carcinoma resected between 1984 and 1996 were retrospectively studied. Cases were divided in three groups according to tumor location: cardia (n = 80); fundus/body (n = 60); antrum (n = 162). The three groups were crosstabulated with clinic and pathologic parameters, such as age, sex, macroscopy, histology, desmoplasia, tumor size, depth of tumor wall penetration, nodal status, venous invasion and stage. Survival rates were calculated for the three locations according to the aforementioned parameters. Univariate survival analysis and Cox regression were performed for each location. Results: Cases from the cardia and fundus/body were similar and distinct from antrum cases according to macroscopy, tumor size, depth of wall penetration, venous invasion, nodal status and stage. Cases from fundus/body were similar to antrum cases and distinct from cardia cases according to gender and Laurén’s classification. An overall difference in survival between the three locations was observed (p = 0.006). Cumulative survival was better for patients with carcinomas in the antrum than in the cardia (p = 0.04) and in the fundus/body (p = 0.003); no significant differences were observed in survival between cardia and fundus/body carcinoma cases. Cox regression identified stage and venous invasion as prognostic factors for patients with carcinomas in the three locations. In the group of cardia tumors, older patients had a worse outcome and in the group of fundus/body carcinomas, large tumors were associated with a poorer survival. Conclusions: Our results show that cardia carcinoma and antrum carcinoma are distinct gastric carcinoma entities whereas fundus/body carcinoma shares some characteristics from both entities.

The HER-2/neu gene or c-erb B-2, localized on chromosome 17q, belongs to a family of tyrosine kinase receptors and shares extensive homology with the epidermal growth factor receptor. c-erb B-2 gene amplification and protein overexpression have been reported in several human cancers. The prognostic value of this genetic alteration in gastric carcinoma is far from being established. In the present study, formalin-fixed, paraffin-embedded gastric carcinoma tissues from 157 patients were evaluated for c-erb B-2 overexpression, by immunohistochemistry using a polyclonal antibody. c-erb B-2 expression was evaluated according to clinical and pathological parameters, and to the survival of the patients. Our results show that: (1). c-erb B-2 was overexpressed in 15.3% of gastric carcinoma cases; (2). c-erb B-2 overexpression was significantly more frequent in cardia (23.8%) and fundus/body (25.0%) carcinomas than in antrum (7.2%) carcinomas; (3). c-erb B-2 overexpression was significantly associated with venous invasion; (4). c-erb B-2 is a prognostic factor for gastric carcinoma.

High risk and positive macroscopic surgical margin status are parameters associated with poor disease-specific survival in GIST patients.

Aim: To assess KIT and PDGFRA mutations frequencies in a Portuguese series of gastrointestinal stromal tumours (GISTs). Methods: 78 GISTs were evaluated for CD117 expression and screened for mutations in KIT (exons 9, 11, 13, 14 and 17) and PDGFRA (exons 12, 14 and 18) genes. Results: KIT activating mutations were identified in 44 (56%) of the 78 GISTs. Forty cases (91%) presented a mutation in KIT exon 11, and 4 (9%) in exon 9. One case showed a 4 bp deletion in intron 14. PDGFRA mutations were observed in 5 cases (6%): 2 (3%) in exon 12 and 3 (4%) in exon 18. Survival analysis was performed in 63 of the 78 GISTs. The presence of mutated KIT was significantly correlated with shorter survival of patients (p = 0.0460), and inversely associated with epithelioid histological type of GISTs (p = 0.0064). Conclusions: Overall, the incidence of both KIT and PDGFRA mutations in these Portuguese series was 63%, being in agreement with other studies, mainly of Iberian populations. The great majority of mutations were located in KIT exon 11, statistically associated with worse prognosis and indicative of favourable response to imatinib-based therapy in this Portuguese series of GISTs.

Previous studies have shown that mucin expression can be used to evaluate differentiation patterns of gastric carcinoma: MUC5AC expression is associated with diffuse type and early gastric carcinomas, and MUC2 expression is associated with mucinous gastric carcinomas. The role played by MUC5B in the evaluation of differentiation and biological behaviour of gastric carcinoma is largely unknown. Our aim was to characterise the pattern of expression of mucins MUC1, MUC2, MUC5AC, MUC5B and MUC6 in a series of 50 gastric carcinomas to evaluate whether MUC5B expression was associated with the clinico-pathological characteristics of the cases and/or with the co-expression of other mucins. A panel of six monoclonal antibodies (HMFG1, SM3, PMH1, CLH2, EU-MUC5Ba and CLH5) was used to determine the expression of mucins (MUC1, MUC1 underglycosylated form, MUC2, MUC5B, MUC5AC and MUC6, respectively) using immunohistochemistry. Cases were considered positive if more than 5% of the cells expressed immunoreactivity for the several mucins evaluated. Our results showed that: (a) expression of MUC5B was observed in 11 cases (22.0%) and was associated with the "unclassified" histological type of gastric carcinoma according to Laurén ( P = 0.03) and with the absence of venous invasion ( P = 0.02); (b) in this series, MUC5B expression had no impact on survival of patients with gastric carcinoma; (c) the expression of MUC5B was associated with the co-expression of MUC5AC ( P = 0.02) and (d) none of the cases with the so-called complete intestinal phenotype of mucin expression expressed MUC5B.