Miguel Villaseca H

Carcinoma incipiente de la vesícula biliar. Estudio clínico-patólogico y pronóstico de 196 casos

Background: There is little information about the behavior of early gallbladder carcinoma. Aim: To report the clinical and pathological features of 196 patients with early gallbladder carcinoma. Material and methods: All patients with gallbladder cancer diagnosed between 1988 and 1997 were reviewed. In 703 of 829 patients, there was information about clinical features and follow up, and were included in this study. All gallbladders were subjected to a complete mapping. When neoplastic cells involved only the mucosa or muscular layer, the tumors were considered as early. Results: One hundred ninety six patients had an early carcinoma (161 women, aged 57.5 years and 35 male, aged 63.4 years). One hundred twenty eight tumors were located in the mucosa and 68 in the muscular layer. Patients with tumors involving the mucosa were younger than those with tumors involving the muscular layer. All tumors were adenocarcinomas, 66% were well differentiated and 32% moderately differentiated. Tumors were not visible macroscopically in 132 cases. Five and 10 years survival was 92%. Subjects of less than 40 years old had a 100% survival at 5 years. A hepatic and lymph node resection was done in 12 patients with tumors infiltrating the muscular layer but in only one, the tumor infiltrated the liver. No difference in survival was observed when a simple cholecystectomy or radical surgery was done. Conclusions: Nearly 25% of gallbladder carcinomas can be classified as early and its diagnosis requires a directed study

Elementos morfológicos pronósticos en el cáncer de la vesícula biliar

Background: The exact survival rates and prognostic factors of gallbladder cancer are still incompletely known. Aim: To report the actuarial survival of patients with gallbladder cancer. Material and methods: Six hundred thirty seven women, aged 59 years old as a mean and 108 men, aged 64 years old as a mean, with gallbladder cancer are reported. Patients were followed for up to 150 months. Results: Two hundred twenty four patients had an early and 521 had an advanced carcinoma. Overall survival was 38% at ten years. Sex or ethnic origin did not influence survival. Early tumors had a 92% survival at 10 years whereas the survival of advanced tumors was 16% at 5 years. Subserous tumors had a 5 years survival of 32% whereas serous tumors had a 5 years survival of 11%. Well-differentiated advanced tumors had a significantly better survival than moderately or poorly differentiated tumors. Vascular or lymphatic infiltration was also associated to a lower survival. All patients with advanced tumors and vascular infiltration died before 5 years. Conclusions: Tumor infiltration and differentiation degree were the most important prognostic independent factors in gallbladder cancer (Rev Med Chile 2002; 130: 387-395)

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).

Mutación del gen p53 en el cáncer de la vesícula biliar

33 formalin fixed paraffin embedded samples of gallbladdercarcinoma (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 ofmicrodissection and K-ras mutations in codon 12 were detected by polymerase chain reactionand restriction fragment length polymorphism (RFLP), using previously reported technique.

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.

Es el cáncer de la vesícula biliar una enfermedad de mal pronóstico en Chile

Gallbladder cancer is frequent in Chile, but it is not uniformly mortal. The diagnosis is usually made after a cholecystectomy. indicated for a symptomatic cholelithiasis. Global survival of gallbladder cancer can be as high as 40% at five years. In 69% of women of less than 30 years old, the tumor is detected in early stages. In these cases, cholecystectomy is the curative procedure, with a 90% survival at five years. According to our experience, cholecystectomies should be performed between 40 and 50 years of age in men and between 30 and 40 years in women. The prognostic factors that should be considered are symptoms associated to lithiasis, age, parity, obesity, size of stones and the size of the gallbladder. If the tumor is detected in early stages, the survival is good. The natural history of the disease would change significantly if all women with symptomatic stones were operated (Rev Med Chile 2002; 130: 1295-1302).

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)

Expresión inmunohistoquímica del complejo E-caderina-catenina en cáncer gástrico: Relación con variables clínico-morfológicas y sobrevida de pacientes

l cancer gastrico es la segunda neoplasia masfrecuente a nivel mundial, despues del cancerpulmonar. Las mayores incidencias se registran enChina, Japon, Europa del Este y Sudamerica. Estaneoplasia ocupa el segundo lugar a nivel mundialen mortalidad, con mejor sobrevida solo en Japon,Australia y Nueva Zelanda, debido principalmenteal diagnostico precoz

Expresión de CD44 (HCAM) en el carcinoma subseroso de la vesícula biliar

BACKGROUND HCAM or CD44 is a multifunctional cell adhesion molecule, related to cell-cell, cell-extracellular matrix interactions and involved in tumor invasion. AIM To study the importance of CD44 expression in subserous gallbladder carcinoma. MATERIAL AND METHODS One hundred five samples (93 female) of subserous gallbladder carcinoma and 33 non tumoral gallbladder were studied. CD44 was stained using the streptavidine-biotin technique, using human anti CD44 antibodies. Eighty subjects with carcinoma were followed for a period up to 105 months. RESULTS Mean age of patients was 62.6 years old, all tumors were adenocarcinoma, all were silent and 13% were well differentiated. CD44 was expressed in all controls and in 91%, the expression was normal. In 57% of cancer samples, CD44 expression was abnormal, in 50% it was less expressed and in 24%, it was not expressed. No differences in CD44 expression was observed between mucosa from control samples and mucosa adjacent to the tumor or superficial or deep tumoral areas. Global five years survival was 40%. No significant differences in survival were observed in those tumors with a lower of absent CD44 expression. Six patients with a higher expression died before 18 months of follow up. CONCLUSIONS Nearly 50% of subserous gallbladder carcinomas show an abnormal CD44 expression.