Biomedical subjects

Iván Roa

Publications and source records attributed to Iván Roa.

26 records · Page 2Linked to original sources

PubMed2003

[Point mutation of TP53 suppressor gene in pre-neoplastic and neoplastic lesions of the stomach].

BACKGROUND: In the current model for the development of gastric cancer, regions of multifocal atrophic gastritis give rise to intestinal metaplasia, dysplasia and finally, adenocarcinoma. AIM: To study the frequency and characteristics of TP53 gene mutations in preneoplastic and neoplastic lesions of the stomach. MATERIAL AND METHODS: DNA sequencing of the TP53 gene was performed in 46 patients with gastric carcinoma. Normal mucosa, intestinal metaplasia and invasive adenocarcinoma tissues were obtained by scraping 6-micron histological sections from formalin-fixed and paraffin-embedded tissue. RESULTS: DNA sequencing of exons 5-9 of the TP53 gene demonstrated a mutation in 31% of patients. These findings were seen both in tumoral tissue (13 cases) and in intestinal metaplasia (2 cases). Most mutations were found in exons 5 and 8, and the majority of them were transitions (10 out of 19 mutations). DISCUSSION: Patients with gastric cancer showed a frequency of TP53 mutations similar to that previously communicated in populations with low gastric cancer risk. Moreover, there was a predominance of transitions, genetic alterations that are identified with carcinogenesis associated with N-nitrosamine compounds. Finally, mutations of TP53 gene were detected in areas of intestinal metaplasia.

Adenocarcinoma↗

PubMed2003

[Microsatellite instability and loss of heterozygosity in neoplastic and preneoplastic gastric lesions].

BACKGROUND: Gastric cancer is the leading cause of cancer deaths in the general population in Chile, with mortality rates as high as 33.7 per 105 in males in the IX region. 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. AIM: To study the frequency of microsatellite instability (MSI) and loss of heterocigozity (LOH) in neoplastic and preneoplastic lesions of gastric carcinoma, especially intestinal metaplasia. MATERIAL AND METHODS: Ninety four gastric cancer biopsies were studied using laser capture microdissection, to obtain well defined cell populations from paraffin-embedded tissues: lymphocytes (control DNA), intestinal metaplasia and gastric cancer areas. Primer flanking microsatellite 15 highly polymorphic regions were used to study MSI and LOH. Radioactive PCR products were electrophoresed and exposed for autoradiography. RESULTS: LOH was observed in 83% of gastric carcinomas and in 54% areas containing intestinal metaplasia. The most commonly altered regions were the CA repeat associated with the p53 gene and the 3p21 region. High grade MSI was observed in 11.7% of gastric cancer preparations and 17% of intestinal metaplasia associated to cancer with MSI-H phenotype. CONCLUSIONS: MSI and LOH were frequently observed in intestinal metaplasia glands in patients with gastric carcinoma. The frequency of MSI-H phenotype in gastric patients was slightly lower than the one described in sporadic colorectal cancer not associated to HNPCC. The high incidence of genetic lesions in intestinal metaplasia area, support the idea that intestinal metaplasia is a genetically highly unstable cell population.

Adenocarcinoma↗

PubMed2003

[Genetic changes in chronic gastritis: study of microsatellite instability and loss of heterozygosity].

BACKGROUND: Multifocal chronic gastritis, associated to intestinal metaplasia, is considered a preneoplastic lesion, closely associated to intestinal type gastric cancer. AIM: To study the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) in areas of chronic gastritis and intestinal metaplasia in gastric biopsies of patients without cancer. MATERIAL AND METHODS: Gastric biopsy samples from 34 patients without cancer (22 with multifocal atrophic gastritis and 12 with diffuse antral gastritis), were studied. Glands from areas of chronic gastritis and intestinal metaplasia and lymphocytes, were collected using laser microdissection of paraffin embedded samples. The analysis of 15 mono and dinucleotide microsatellites was used to assess LOH and MSI. RESULTS: LOH and MSI were found in some of the markers in 55% (12/22) and 59% (13/22) of cases with intestinal metaplasia, respectively. Only one of 12 areas with diffuse atrophic gastritis had MSI and a different area had LOH (p < 0.05 or less, when compared with areas of multifocal atrophic gastritis). Three areas of normal epithelium in patients with multifocal atrophic gastritis, also had alterations. Most of these alterations were concordant with adjacent areas with intestinal metaplasia. CONCLUSIONS: LOH and MSI was found in areas of intestinal metaplasia in more than half of the studied cases and in few areas of atrophic gastritis without intestinal metaplasia. These findings suggest that genotypic alterations may precede phenotypic modifications and that intestinal metaplasia is a preneoplastic lesion.

Chronic Disease↗

PubMed2003

[Human papilloma virus (HPV) typing in preneoplastic and neoplastic lesions of the uterine cervix in the IX region-Chile].

BACKGROUND: Uterine cervical cancer (UCC) is an important public health problem in Chile. Although HPV infection has been established as the main cause of UCC, little is known of its frequency and distribution in our population. AIM: To determine the presence and frequency of viral genotypes in uterine cervical specimens with preneoplastic and neoplastic lesions. MATERIAL AND METHODS: Two nested consensus PCRs followed by identification of amplified product by dot-blot hybridization and restriction fragment length polymorphism (RFLP) were used to analyze 175 biopsies. RESULTS: Detection of HPV was 40% in cases without histological lesion, 88% in low grade lesions, 89% in high grade lesions (HGL) and 93.5% in invasive carcinoma. Of all HPV positive cases, 89.5% were classified as high risk and only a 4.9% of HPV cases were of low risk type. Six percent of cases had multiple infections. Distribution of viral genotypes according to RFLP was: HPV33 (25.3%), 16 (18.7%), 52 (13.3%), 31 (12%), 35 (6.6%), 18 (2.7%). CONCLUSIONS: Most HPV found in biopsies with HGL and UCC were of high risk genotype. The elevated presence of high risk HPV in patients without cervical lesions may be a factor that explains the high percentage of UCC cases in our region. Most common viral types were: HPV16, 31, 33 and 52. Viral detection and typing may provide valuable information for patient selection and follow up and for allocation of resources.

Adolescent↗

PubMed2002

[Morphological prognostic elements in gallbladder cancer].

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.

Adenocarcinoma↗

PubMed2002

[Detection of BCR-ABL gene sequences using RT-PCR in patients with leukemia in the IX region. Chile].

BACKGROUND: The BCR-ABL fusion gene is the molecular expression of the Philadelphia chromosome. This cytogenetic aberration is the most frequent alteration found in leukemias, which is produced by the translocation t(9;22). Two different fusion proteins are produced depending on the break point (210 kD and 190 kD). The detection of this gene has both diagnostic and prognostic importance, associated with poor prognosis in acute lymphoblastic leukemia (ALL). AIM: To detect BCR-ABL gene sequences in patients with leukemia from the IX Region of Chile. MATERIAL AND METHODS: We studied 58 patients: 5 chronic myeloid leukemia (CML), 35 ALL, 15 acute myeloid leukemia (AML) and 3 biphenotypic leukemia. The gene sequences were detected using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: BRC-ABL gene sequences were positive in all patients with CML, 2 of 35 ALL (one child and one adult). The remaining patients were negative. We found p210 and p190 co-expression in 2 CML and 1 ALL. CONCLUSIONS: Our results are in agreement with other reports. The detection of these and other genetic alterations will allow us to have invaluable diagnostic and prognostic information from our patients with leukemia.

Acute Disease↗

PubMed2002

[Is gallbladder cancer a disease with bad prognosis?].

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.

Adult↗

PubMed2002

[Subserous gallbladder carcinoma: expression of cadherine-catenine complex].

BACKGROUND: Subserous gallbladder carcinoma is difficult to diagnose and treat. There are no tissue markers with prognostic value in this type of tumor. AIM: To study the immunohistochemical expression of E-cadherin alpha and beta catenin in subserous gallbladder carcinoma. PATIENTS AND METHODS: One hundred seventeen subjects (103 women and 14 men aged 62 and 69 years as a mean, respectively), were studied. Thirty five gallbladder samples without evidence of cancer were used as controls. Expression of markers was studied with standard immunohistochemical techniques for formalin fixed and paraffin embedded tissue. RESULTS: Ninety seven percent of tumors were adenocarcinoma. A lower or absent expression of E-cadherin, alpha catenin and beta catenin was observed in 26, 33 and 29% of tumors, respectively. Actuarial five years survival was 37%. No association between macroscopic features of the tumor and survival was observed. Well differentiated tumors had a 73% survival, whereas less differentiated tumors had a 30% survival. Tumors with a normal expression of the markers had a slightly better survival, although not significant (p = 0.06). CONCLUSIONS: Approximately 30% of subserous gallbladder carcinoma have an abnormal expression of E-cadherin, alpha catenin and beta catenin. This abnormal expression has no relationship with prognosis and is probably secondary to the aberrant genic expression of the tumor.

Adult↗