Oscar Tapia E

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).

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)

Mutación del gen K-ras en el cáncer de la vesícula biliar

BACKGROUND Different K-ras mutation frequencies in gallbladder cancer have been reported. AIM To study the frequency of K-ras gene mutations in advanced gallbladder carcinoma not associated to anomalous junction of pancreatic-biliary duct (AJPBD). MATERIAL AND METHODS 33 formalin fixed paraffin embedded samples of gallbladder carcinoma (30 women, age range 32-86 years) were selected. Pancreatic cancer tissue with K-ras mutations was used as control. DNA was extracted from the histological section by mean of microdissection and K-ras mutations in codon 12 were detected by polymerase chain reaction and restriction fragment length polymorphism (RFLP), using previously reported technique. RESULTS Most cases were poorly differentiated adenocarcinomas. K-ras mutation was detected in 10 cases (30%) samples. No differences in K-ras mutation frequency between subserous and serous tumors were detected and no relation between histological features and the mutation was observed. CONCLUSIONS K-ras mutation in codon 12 is present in 30% in our advanced gallbladder carcinomas. The study of K-ras mutation in preneoplastic lesions and early carcinonmas will be important to determine the role of this gene in the gallbladder carcinogenesis in Chile.

Mutación del gen K-ras en tumores pancreático-biliares

Background: The ras gene family (H-ras, N-ras and K-ras) are oncogenes that mutate frequently in human cancer, specially in tumors of the biliary tract and pancreas. Aim: To determine the frequency of K-ras gene codon 12 mutation in pancreatic and biliary tumors. Material and Methods: Samples of 35 gallbladder, 15 ampulla of Vater, 10 biliary tract and 9 pancreatic tumors, were analyzed. The tumor tissue was microdissected from paraffin embedded biopsies. The mutation was detected by a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: Overall, 46% of samples had K-ras gene mutations. Mutation frequency was 80, 56, 50 and 29% for ampulla of Vater, pancreatic, biliary tract and gallbladder tumors, respectively. When compared with the rest, gallbladder tumors had a significantly lower frequency of the mutation. Median survival for biliary tract tumors was 6 months, compared with 65 months for gallbladder tumors (p <0.05). Conclusions: Gallbladder carcinoma had the lower frequency of K-ras mutation, when compared with pancreatic, biliary tract and ampulla of Vater tumors (Rev Med Chile 2005; 133: 1434-40). (Key Words: Biliary tract neoplasms; Gallbladder neoplasms; Genes, ras; Pancreatic 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.

Hidatidosis cerebral: aspectos clínicos e imagenológicos. Reporte de 4 casos

In only 2% of all cases of hydatidosis, the cysts are located in the brain. We report a 12-year-old male, a 5-year-old girl and a 19-year-old female consulting for intracranial hypertension and a 13-year-old male consulting for a left hemiparesis. Imaging studies found intra-cerebral cysts with characteristics of hydatidosis in all. All lesions were completely removed surgically and the pathological study of the excised piece confirmed the diagnosis of hydatidosis.

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.

Mucormicosis cutánea primaria: a propósito de dos casos. Revisión de la literatura

Mucormycosis or zygomycosis is a rare opportunistic infection caused by aerobic saprophytic fungus that belongs to the class of Zygomycetes Mucorales family. These organisms live in the environment and enter the body by air, gastrointestinal or skin routes, through solutions of continuity of the skin. This microorganism is generally not pathogenic for immunocompetent hosts, being the development of the disease linked with the immune status of the subject. Its mortality is around 50-60%; sometimes in spite of early diagnosis and treatment initiation it has a fatal course. Six clinical forms of mucormycosis are described: rhinocerebral, cutaneous, pulmonary, disseminated, gastrointestinal and miscellaneous form. Two cases of patients with primary cutaneous mucormycosis diagnosed in the Pathology Unit of Hernan Henriquez Aravena Hospital of Temuco, Chile are presented here.

Tuberculosis Intestinal Secundaria: Hallazgos Morfológicos en un Caso con Desenlace Fatal

La tuberculosis gastrointestinal (TB GI) representa el 3-5% de todos los casos de TB extrapulmonar, reportandose que hasta el 20% de los sujetos con TB pulmonar presentan manifestaciones extra-pulmonares que incluyen enfermedades intra-abdominales, sin embargo, se desconoce la real incidencia del compromiso intestinal. La region ileocecal representa el sitio anatomico mas frecuentemente afectado (85-90%), siendo actualmente la colonoscopia la herramienta diagnostica de mayor utilidad. Se presentan los hallazgos morfologicos del examen post-mortem de una paciente en estudio por baja de peso y masa en region cecal. La necropsia realizada en la Unidad de Anatomia Patologica del Hospital Hernan Henriquez Aravena de Temuco concluyo una TB pulmonar bilateral con compromiso secundario intestinal y linfonodal.