Identificación de asociaciones clínico-patológicas e hipermetilación de genes supresores de tumores en cáncer gástrico difuso a través de análisis de Hierarchical clustering / Hierarchical clustering analysis to detect associations between clinical and pathological features of gastric tumors and hypermethylation of suppressor genes

Background:Methylation is an inactivation mechanism for tumor suppressor genes, that can have important clinical implications. Aim: To analyze the methylation status of 11 tumor suppressor genes in pathological samples of diffuse gastric cancer. Material and methods: Eighty three patients with diffuse gastric cancer with information about survival and infection with Epstein Barr virus, were studied. DNA was extracted from pathological slides and the methylation status of genes p14, p15, p16, APC, p73, FHIT, E-caderin, SEMA3B, BRCA-1, MINT-2 y MGMT, was studied using sodium bisulphite modification and polymerase chain reaction. Results were grouped according to the methylation index or Hierarchical clustering (TIGR MultiExperiment Viewer). Results: Three genes had a high frequency of methylation (FHIT, BRCA1, APC), four had an intermediate frequency (p15, MGMT, p14, MINT2) and four had a low frequency (p16, p73, E-cadherin, SEMA3B). The methylation index had no association with clinical or pathological features of tumors or patients survival. Hierarchical clustering generated two clusters. One grouped clinical and pathological features with FHIT, BRCA1, and APC and the other grouped the other eight genes and Epstein Barr virus infection. Two significant associations were found, between APC and survival and p16/p14 and Epstein Barr virus infection. Conclusions: Hierarchical clustering is a tool that identifies associations between clinical and pathological features of tumors and methylation of tumor suppressor genes.

Características clínico-moleculares del cáncer gástrico cardial asociado al virus Epstein Barr / Clinical and molecular features of cardial gastric cancer associated to Epstein Barr virus

Background: Mortality caused by cardial gastric cancer in Chile, is increasing. Previously we demonstrated an association between Epstein Barr virus and this specific location of gastric cancer. Aim: To perform a clinical and molecular characterization of cardial gastric cancer associated to Epstein Barr virus. Material and methods: Epstein Barr virus was identified in 93 cardial gastric tumors, by in situ hybridization. Clinical and pathological features, survival and expression of p53 and c-erbB2 were compared between tumors with or without the presence of the virus. Results: Twenty two (23.6%) tumors expressed Epstein Barr virus. No difference in sex or age of patients with tumors positive or negative for the virus was observed. Epstein Barr positive tumors had a tendency to have a higher frequency of Bormann III endoscopic appearance and a lower frequency of p53 accumulation (p=0.06). Five years survival was 67% and 42% of tumors positive and negative for the presence of the virus, respectively (p=0.57). Conclusions: Our results, although not significant, show a tendency towards unique characteristics of cardial gastric tumors associated to Epstein Barr virus.

Reordenamiento de inmunoglobulinas en el diagnóstico diferencial del linfoma gástrico primario / Immunoglobulin rearrangement in the differential diagnosis of primary gastric lymphoma

Background: The traditional methods to distinguish Chronic Follicular Gastritis and Primary Gastric Lymphoma do not allow an adequate definitive diagnosis in a significant number of cases. The Molecular Biology diagnostic methods are based on the rearrangement of immunoglobulin genes. The polymerase chain reaction (PCR) specifically amplifies this rearrangement and allows molecular analysis of minimal tissue samples obtained with endoscopical biopsies. Aim: To test the usefulness of this PCR method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma. Material and methods: We analyzed the endoscopical biopsies of six Chronic Follicular Gastritis cases and eight surgically treated Primary Gastric Lymphoma cases, six with the correct diagnosis in the endoscopical biopsies and two with a diagnosis of Chronic Follicular Gastritis. Results: A policlonal immunoglobulin rearrangement was found in the six cases with Chronic Follicular Gastritis. A monoclonal arrangement was found in 5 of 6 biopsies with the diagnosis of Primary Gastric Lymphoma. The same monoclonal rearrangement was observed in the two biopsies incorrectly diagnosed as Chronic Follicular Gastritis. Conclusions: PCR analysis of immunoglobulin rearrangement is a useful method in the differential diagnosis between Chronic Follicular Gastritis and Primary Gastric Lymphoma

Estudio anátomo patológico de 86 adenomas gástricos: experiencia en 14 años / Anatomic-pathological study of 86 gastric adenomas: experience in 14 years

To analyze the clinical presentation, pathological aspect and trealment of gastric adenomas, a retrospective analysis of 75 patients aged 26 to 88 years in whom a gastric adenoma was diagnosed. Seventy one patients had elevated endoscopical lesions and two had depressed or flat lesions. Ninety percent of lesions were located in the gastric antrum. Pathological study detected 6 focal carcinomas within the adenomas and 5 concomitant carcinomas located elsewhere in the stomach. Fifty four patients were subjected to endoscopical resection. Among patients with focal carcinomas, a gastrectomy was performed in four and endoscopical resection in two. Gastric adenomas must be considered in the differential diagnosis of gastric elevated lesions and may be confused in early gastric cancer. There is a histological resemblance between adenomas and gastric dysplasia descibed by several authors though only in our cases and in the Japanese literature the adenoma is referred to as mostly a polypoid sessile lesion

Linfoma gástrico primario: análisis de 86 casos / Primary gastric lymphoma: analysis of 86 cases

We report the retrospective analysis of 86 patients with primary gastric lymphoma diagnoses in a period of 12 years, that constitute 5.6 percent of malignant gastric lesions diagnosed in that lapse. Upper gastrointestinal endoscopy diagnosed a malignant lesion in 93 percent and lymphoma in 36 percent of cases. Endoscopic biopses disclosed malignant lesions in 79 cases (93 percent) and were diagnostic of lymphoma in 70 (82 percent). All patients were operated, including the seven subjects in which the biopsy did not show malignant lesions; the surgical indication on the latter was based in clinical grounds. The macroscopic examination of the surgical piece showed ilcerated lesions in 45 (52 percent) and mixed lesions (ulcerated and protruded with and without multiple erosions) in 15 (18 percent) patients. 17 patients (33 percent) had an early lesion of the MALT type (mucosa associated lymphoid tissue) and 87 percent of lesions were of low or intermediate histological type