Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CDKN2A promoter methylation is related to the tumor location and histological subtype and associated with Helicobacter pylori flaA(+) strains in gastric adenocarcinomas

Promoter hypermethylation of CDKN2A (p16INK4A protein) is the main mechanism of gene inactivation. However, its association with Helicobacter pylori infection is a controversial issue. Therefore, we examined a series of gastric adenocarcinomas to assess the association between p16INK4A inactivation and H. pylori genotype (vacA, cagA, cagE, virB11 and flaA) according to the location and histological subtype of the tumors. p16INK4A expression and CDKN2A promoter methylation were found in 77 gastric adenocarcinoma samples by immunohistochemistry and methylation-specific PCR, respectively. Helicobacter pylori infection and genotype were determined by PCR. A strong negative correlation between immunostaining and CDKN2A promoter region methylation was found. In diffuse subtype tumors, the inactivation of p16INK4A by promoter methylation was unique in noncardia tumors (p = 0.022). In addition, H. pylori-bearing flaA was associated with non-methylation tumors (p = 0.008) and H. pylori strain bearing cagA or vacAs1m1 genes but without flaA was associated with methylated tumors (p = 0.022 and 0.003, respectively). Inactivation of p16INK4A in intestinal and diffuse subtypes showed distinct carcinogenic pathways, depending on the tumor location. Moreover, the process of methylation of the CDKN2A promoter seems to depend on the H. pylori genotype. The present data suggest that there is a differential influence and relevance of H. pylori genotype in gastric cancer development.

Gastric adenocarcinoma and Helicobacter pylori: Correlation with p53 mutation and p27 immunoexpression

Introduction: Helicobacter pylori infection is an established risk factor for gastric cancer development, but the exact underlying mechanism still remains obscure. The inactivation of tumor suppressor genes such as p53 and p27(KIP1) is a hypothesized mechanism, although there is no consensus regarding the influence of H. pylori cagA(+) in the development of these genetic alterations. Goals: To verify the relationship among H. pylori infection, p53 mutations and p27(Kip1) Protein (p27) expression in gastric adenocarcinomas (GA) seventy-four tissues were assayed by PCR for H. pylori and cagA presence. Mutational analysis of p53 gene was performed by single-strand conformation polymorphism (SSCP). Seventy tissues were analyzed by an immunohistochemical method for p27 expression. Results: From the samples examined, 95% (70/74) were H. pylori positive, 63% cagA(+). Altered p53 electrophoretic mobility was found in 72% of cases and significantly more frequent in the presence of cagA. Considerable reduction in p27 expression (19%) was found with a tendency for association between cagA(+) and p27(-), although the results were not statistically significant. Concomitant alterations of both suppressor genes were detected in 60% of cases. In the cases cagA(+), 66.7% of them had these concomitant alterations. Conclusions: The data suggest that H. pylori cagA(+) contributes to p53 alteration and indicate that concomitant gene inactivation, with reduced p27 expression, may be a mechanism in which H. pylori can promote the development and progression of gastric cancer. (C) 2010 Elsevier Ltd. All rights reserved.

Gingival metastasis from salivary duct carcinoma of the parotid gland

Background: This article reports a rare case of metastasis of salivary duct carcinoma of the parotid gland to the gingiva and reviews the occurrence of metastatic processes to the oral mucosa.Methods: A 67-year-old white male presented with a chief complaint of a painless nodular tissue growth on the gingiva with reportedly 5 months of evolution. The intraoral examination revealed a reddish, superflcially ulcerated nodular lesion (similar to 2 cm in diameter) on the right mandibular buccal attached gingiva, and the clinical aspect was that of a benign reactive lesion. The patient had undergone a parotidectomy for removal of a salivary duct carcinoma of the parotid gland almost 1 year before. A biopsy of the gingival lesion was performed, and the biopsied tissue was forwarded for histopathologic examination.Results: The analysis of the histopathologic sections of the gingival lesion revealed histomorphologic characteristics very similar to those of the primary parotid gland tumor. The definitive diagnosis was gingival metastasis from a salivary duct carcinoma of the parotid gland. The patient died of complications of a pulmonary metastasis I month after the diagnosis of the oral metastatic lesion.Conclusions: Gingival lesions that mimic reactive and hyperplastic lesions may be metastases from malignant neoplasias of diverse origins. An accurate and timely diagnosis is crucial to establish proper and immediate treatment of the metastatic tumor and possibly identify an occult primary malignant neoplasia.

Inactivation of COX-2, HMLH1 and CDKN2A Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and Helicobacter pylori Genotype

Objective: We aimed to evaluate the inactivation of COX-2, HMLH1 and CDKN2A by promoter methylation and its relationship with the infection by different Helicobacter pylori strains in gastric cancer. Methods: DNA extracted from 76 H. pylori-positive gastric tumor samples was available for promoter methylation identification by methylation-specific PCR and H. pylori subtyping by PCR. Immunohistochemistry was used to determine COX-2, p16(INK4A) and HMLH1 expression. Results: A strong negative correlation was found between the expression of these markers and the presence of promoter methylation in their genes. Among cardia tumors, negativity of p16(INK4A) was a significant finding. on the other hand, in noncardia tumors, the histological subtypes had different gene expression patterns. In the intestinal subtype, a significant finding was HMLH1 inactivation by methylation, while in the diffuse subtype, CDKN2A inactivation by methylation was the significant finding. Tumors with methylated COX-2 and HMLH1 genes were associated with H. pylori vac A s1 (p = 0.025 and 0.047, respectively), and the nonmethylated tumors were associated with the presence of the gene flaA. Conclusions: These data suggest that the inactivation of these genes by methylation occurs by distinct pathways according to the histological subtype and tumor location and depends on the H. pylori genotype. Copyright (C) 2011 S. Karger AG, Basel

Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies

OBJECTIVETo determine the current status of the literature regarding the clinical efficacy and complication rates of cryoablation vs radiofrequency ablation in the treatment of small renal tumours.METHODSA review of the literature was conducted. There was no language restriction. Studies were obtained from the following sources: MEDLINE, EMBASE and LILACS.Inclusion criteria were (i) case series design with more than one case reported, (ii) use of cryoablation or radiofrequency ablation, (iii) patients with renal cell carcinoma and, (iv) outcome reported as clinical efficacy.When available, we also quantified the complication rates from each included study.Proportional meta-analysis was performed on both outcomes with a random-effects model. The 95% confidential intervals were also calculated.RESULTSThirty-one case series (20 cryoablation, 11 radiofrequency ablation) met all inclusion criteria.The pooled proportion of clinical efficacy was 89% in cryoablation therapy from a total of 457 cases. There was a statistically significant heterogeneity between these studies showing the inconsistency of clinical and methodological aspects.The pooled proportion of clinical efficacy was 90% in radiofrequency ablation therapy from a total of 426 cases. There was no statistically significant heterogeneity between these studies.There was no statistically significant difference regarding complications rate between cryoablation and radiofrequency ablation.CONCLUSIONSThis review shows that both ablation therapies have similar efficacy and complication rates.There is urgency for performing clinical trials with long-term data to establish which intervention is most suitable for the treatment of small renal masses.

Follicular thyroid carcinoma in dogs. Report of cases

The treatment of choice for these cases was surgical removal. In both cases the diagnostic was infiltrative follicular carcinoma of thyroid. The first animal did not present a good recovery after the surgery, and died four hours after the procedure. In the second case, the diagnosis was more precocious and antineoplastic chemotherapy was used after the surgery. At the time of submission of this manuscript, this animal had survived for foully months. Currently, there is a need to define the protocols of chemotherapy to avoid relapse and metastases, in order to increase the life expectancy in dogs with thyroid neoplasm.

Galectin-3 Overexpression in Invasive Laryngeal Carcinoma, Assessed by Computer-assisted Analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)