Juan Carlos Araya O

Patrón de metilación génico en el cáncer de mama

: We found methylation inat least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. Thefrequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHIT were41.4%, 11.4%, 52.9%, 70% y 42.9%, respectively. We found a relationship between CDKN2A me-thylation and better survival (p=0.002). CDH1 methylation and poor histological differentiation(p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=0.03), APC methylation and larg-er tumor size (p <0.05), FHIT methylation and lack of estrogen receptor IHC expression (p <0.05).

Inactivación del gen CDKN2A (p16) en cáncer de la vesícula biliar

: We analyzed themethylation status of the promoter region of the CDKN2A gene in gallbladder adenocarcinomasusing methylation specific PCR (MSP). We also used microsatellite markers near the CDKN2Agene to detect allelic imbalance (AI) and examined the tumors by immunohistochemistry (IHC)for p16 expression.

Estudio de patrones de metilación génica en tumores del tubo digestivo

Background: The loss of tumor suppresor gene function damages the defensive mechanisms that protect the indemnity of genetic material. Promoter gene methylation is one of the inactivation mechanisms of suppressor genes. Aim: To study the methylation pattern of a group of genes in biopsy samples of gastrointestinal tumors. Material and methods: Forty eight gastric, 25 gallbladder, 24 colon and 6 pancreas cancer biopsy samples were randomly selected. The methylation pattern of CDH1, FHIT, CDKN2A, APC and MLH1 genes, was studied using a specific polymerase chain reaction test for methylation. Demographic, morphological and follow up variables of patients bearing the tumors were also analyzed. Results: The general methylation frequency of CDH1, FHIT, CDKN2A, APC and MLH1 genes was 64.1, 56, 39.8, 18.1 and 34% respectively. In gastric cancer samples there was a correlation between APC gene methylation and well differentiated tumors; between CDH1 methylation and Lauren diffuse type and the presence of three or more metastasic lymph nodes; between FHIT, CDKN2A and CDH1 gene methylation and male gender. In iess differentiated gallbladder tumors, the frequency of CDH1 methylation was higher. There was a tendency towards a lower survival in colon and gastric cancer when MLH1 (p =0.07) y CDKN2A (p= 0.06) were methylated, respectively. Conclusions: An abnormal methylation pattern was associated with morphological features in gastric and gallbladder cancer and with a tendency towards a lower survival in colon and gastric cancer

Estudio del patrón de metilación génico en el cáncer gástrico en Chile

Background: Promoter genomic DNA methylation is an important inactivation mechanism of tumor suppressor genes. This genetic-molecular pathway for cancer may separate a subset of patients with different prognoses and eventually different responses to specific therapies. Aim: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with gastric cancer (GC) and the relationship with its morphological features and biological behavior. Material and methods: Forty-seven fresh-frozen GC samples were selected. The methylation-specific PCR (MSP) test was used to analyze promoter methylation status for genes MLH1, CDKN2A (p16), APC, CDH1 (Cadherin E) and FHIT. Follow-up and complete morphological features were obtained for all cases. Results: We found methylation in at least one of the genes studied in 83% of the cases. The frequencies of promoter hypermethylation of MLH1, CDKN2A, APC, CDH1 and FHIT were 31%, 43%, 46%, 80% y 62%, respectively. We found a relationship between APC methylation and good histological differentiation (p=0.03); CDH1 methylation with diffuse type by Lauren and 3 or more metastasic lymph nodes (p <0.05); FHIT, CDKN2A and CDH1 methylation and female condition (p <0.04). We also found a non-significant relationship between CDKN2A methylation and better survival (p=0.07). Conclusions: The high frequency promoter methylation found confirms its importance in gastric carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search for new criteria in clinical and therapeutic decision making (Rev Med Chile 2005; 133: 874-80). (Key Words: DNA methylation; Promoter regions (Genetics); Stomach neoplasms)

Linfoadenitis criptococócica mesentérica: Una rara causa de abdomen agudo. Caso clínico

Cryptococcosis is an invasive mycotic infection caused by Cryptococcus neoformans, an encapsulated, yeast-like fungus. It is considered an opportunist infection, since it mainly affects immunocompromised subjects. However there are isolated reports of the infection in immunocompetent subjects. Cryptococcal infection of intra-abdominal organs or tissues is extremely rare. We report a 21-year-old HIV positive male that, during the treatment of a meningeal cryptococcosis, presented a clinical picture of an acute abdomen suggesting acute appendicitis. The patient was operated, finding enlarged mesenteric lymph nodes forming conglomerates and a macroscopically normal appendix. The conglomerated lymph nodes and the appendix were excised. The pathological study of the surgical piece revealed an intra abdominal cryptococcal lymphadenitis and a normal appendix.

Helicobacter pylori y gastritis crónica: relación entre infección y actividad inflamatoria en población de alto riesgo de cáncer gástrico

Background: Helicobacter pylori has been involved in gastric epithelial cell damage and gastric gland loss or atrophy. Aims: to evaluate role of Helicobacter pylori infection in acute and chronic changes of chronic gastritis in a high gastric cancer-risk population. Material and methods: 200 patients with chronic gastritis were selected from pathological files of Temuco Hospital. A complete histopathological protocol was fulfilled considering the presence of infection by Helicobacter pylori-like-organism (HLO), acute and chronic inflammatory infiltrate, epithelial cell damage and epithelial cell regeneration. Results: 82% of patients showed infection by HLO. Moreover, this infection reached a frequency of 92.7% in gastric ulcer patients and 94.4% in duodenal ulcer patients. A statistically significant positive correlation was found between HLO infection and polymorphonuclear infiltrate, Iymphocytic infiltrate, mucus depletion and epithelial regenerative activity. There was not a statistical correlation between HLO infection and atrophy. Finally, 90% of patients with multifocal atrophic gastritis and 100% of patients with diffuse antral gastritis had HLO infection. Conclusions: HLO gastric infection frequently caused acute inflammatory changes in gastric mucosa with chronic gastritis. Sometimes these changes were severe, with marked polymorphonuclear migration throughout epithelium and severe epithelial cell damage. Recovery of these changes could be considered as a goal in Helicobacter pylori eradication therapy decision

Puntaje de Gleason en cáncer de próstata: Correlación de la biopsia por punción y prostatectomía radical

Background: Gleason pathological score in prostate cancer is an importantprognostic indicator. However, the concordance between the score of trans rectal needle biopsies and the final score of the surgical piece may be variable. Aim: To analyze the concordance between Gleason scores of trans rectal prostate biopsies and those of the surgical piece obtained after prostatectomy. Material and Methods: Retrospective analysis of 168 pathological records of radical prostatectomies, performed between 1993 and 2009. All these patients had also a trans rectal biopsy performed previously. Patients with less than 12 tissue cylinders obtained during the trans rectal biopsy or incomplete data were not included in this analysis. Results: Sixty eight percent of trans rectal biopsies had Gleason scores that were concordant with those of the surgical piece. The score was higher or lower in 27 and 10% of biopsies, respectively. Conclusions: Gleason scores of trans rectal biopsies and those of the surgical piece were concordant in 68% of cases in this series of pathological records.

Relación de la genotipificación de Helicobacter pylori con la forma e intensidad de la gastritis en población adulta portadora de patología gástrica benigna

gene had genotypes s2/m2, s1/m1 and s1/m2 in 36, 25 and 8% of cases respectively, cagA gene was present in 49% of infected patients. iceA gene had genotypes iceA 1 ad iceA 2 in 15 and 60% of patients respectively. The presence of cagA or alleles s1/m1 and s1/m2 of vacA gene was directly correlated with polymorphonuclear infiltration and the severity of epithelial damage. The genotype s2/m2 of vacA gene was significantly associated with a milder or absent mucosal damage. No association was found between iceA alleles and the pathological features of gastritis. Conclusions: Alleles of vacA and cagA genes of H pilory are associated with the severity of gastric mucosal damage (Rev Med Chile 2004; 132: 1345-13). (Key Words: Gastritis; Genes, bacterial; Helicobacter pylori)

Inestabilidad microsatelital y pérdida de la heterocigocidad en lesiones neoplásicas y preneoplásicas gástricas

: Gastric cancer is the leading cause of cancer deaths inthe general population in Chile, with mortality rates as high as 33.7 per 105 in males in the IX re-gion. A chain of genetic and morphological events precedes the intestinal type of gastric carcinoma.One of them is the called multifocal atrophic gastritis often associated with intestinal metaplasia.

Descripción clínico-morfológica y factores pronósticos en carcinomas de apéndice cecal: Estudio de cohorte

Appendiceal malignant tumors. Review of 84 cases Background: Malignant appendiceal tumors account for only 0.5% of all gastrointestinal tumors and there are usually diagnosed during the pathological study of excised appendices. Aim: To assess the factors infl uencing the survival of patients with appendiceal carcinomas. Material and Methods: Retrospective re- view of records of all primary appendiceal carcinomas diagnosed in the pathology unit of a regional hospital between 1993 and 2008. The surgical procedure, clinical history, morphological features of tumor and survival were recorded. Results: Eighty four patients aged 32 ± 15 years (44 women) with appendiceal carcinoma were identifi ed. In 93% of patients, the clinical diagnosis was acute appendicitis. Sixty one patients (73%) had a carcinoid tumor, 20 (24%) an adenocarcinoma and three (3%), an adenocarcinoid tumor. Preoperative suspicion of a malignant tumor, level of tumor infi ltration, pathological type, involvement of surgical borders, tumor size over 2 cm in the case of carcinoid tumors and the degree of differentiation of adenocarcinomas, had prognostic value. For adenocarcinomas, performing a right hemicolectomy signifi cantly improved survival. Conclusions: Carcinoid tumors are the most common malignant tumor of the appendix. A right hemicolec- tomy may improve the survival of patients with appendiceal adenocarcinomas.