Amadeu Pimenta

c-erb B-2 Expression Is Associated with Tumor Location and Venous Invasion and Influences Survival of Patients with Gastric Carcinoma:

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.

Loss of RKIP expression is associated with poor survival in GISTs.

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.

Clinicopathologic profiles and prognosis of gastric carcinomas from the cardia, fundus/body and antrum.

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.

Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs

Aims:  Gastrointestinal stromal tumours (GISTs) are commonly driven by oncogenic mutations in KIT and PDGFRA. However, 10–40% of these patients are wild‐type for these genes. The prognostic significance of wild‐type GISTs is controversial, and they rarely respond to imatinib. The aim of this study was to elucidate the molecular lesions underlying wild‐type GISTs tumorigenesis.

Acute diverticulitis in younger patients: any rationale for a different approach?

AIM To compare the natural history and course of acute diverticulitis in a younger age group with an older population and to evaluate whether younger patients should be managed differently. METHODS This study was a retrospective review of 157 patients treated with acute diverticulitis between January 1, 2004 and December 31, 2007. Diverticulitis was stratified according to the Hinchey classification. Patients were divided into 2 populations: group A ≤ 50 years (n = 31); group B > 50 years (n = 126). Mean patient follow-up was 15 mo. RESULTS The median age was 60 years. A significantly higher proportion of patients in group B presented with complicated diverticulitis (36.5% vs 12.9%, P = 0.01). Recurrence was more frequent in group A (25.8% vs 11.1%, P = 0.03) and the mean time-to-recurrence was shorter (12 mo vs 28 mo, P = 0.26). The most severe recurrent episodes of acute diverticulitis were classified as Hinchey stage I and none of the patients required emergency surgery. In multivariate analysis, only age (P = 0.024) was identified as an independent prognostic factor for recurrence. CONCLUSION 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.

Molecular alterations of KIT and PDGFRA in GISTs: evaluation of a Portuguese series

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.

MUC5B expression in gastric carcinoma: relationship with clinico-pathological parameters and with expression of mucins MUC1, MUC2, MUC5AC and MUC6

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.

Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma

Aims:  Mutations in the gene coding for p53 protein are among the most frequent genetic alterations observed in human cancers. The relevance and biological significance of p53 expression in gastric carcinoma are far from being fully established. The aim of our study was to evaluate the influence of p53 detected by immunohistochemistry in the clinicopathological behaviour of a series of gastric carcinoma cases.

Primary gastric adenosquamous carcinoma in a Caucasian woman: a case report

IntroductionMost gastric tumors are adenocarcinomas. Primary gastric adenosquamous carcinoma is a rare malignancy, mostly associated with Asian populations. It constitutes less than one percent of all gastric carcinomas and its clinical presentation is the same as adenocarcinoma. It occurs more frequently in the proximal stomach, usually presents with muscular layer invasion and tends to be found in advanced stages at diagnosis, with a worse prognosis than adenocarcinoma.Case presentationWe report the case of an 84-year-old Caucasian woman with an adenosquamous carcinoma extending to her serosa with lymphatic and venous invasion (T3N1M1). Nodal and hepatic metastasis presented with both cellular types, with dominance of the squamous component.ConclusionsAdenosquamous gastric cancer is a rare diagnosis in western populations. We present the case of a woman with a very aggressive adenosquamous carcinoma with a preponderance of squamous cell component in the metastasis. Several origins have been proposed for this kind of carcinoma; either evolution from adenocarcinoma de-differentiation or stem cell origin might be possible. The hypothesis that a particular histological type of gastric cancer may arise from stem cells might be a field of research in oncological disease of the stomach.

Granular Cell Tumour and Leiomyomatosis of the Esophagus — a Non-Coincidental Association?

One case of esophageal granular cell tumour (GCT) associated with diffuse leiomyomatosis of the distal esophagus is presented. The rarity of each of the lesions per se raises the possibility that the association between GCT and diffuse leiomyomatosis, a previously unreported finding, is not coincidental. In view of the present knowledge on both conditions we suggest that an underlying genetic alteration may be responsible for the hereby described association.