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Iván Roa

Publications and source records attributed to Iván Roa.

At least 19 recordsLinked to original sources
PubMed2006

[Immunohistochemical expression of the E-cadherin-catenin complex in gastric cancer].

BACKGROUND: The E-cadherin/catenin complex plays an essential role in the control of epithelial differentiation. Abnormal expression in tumors correlates with histological grade, advanced stage and poor prognosis. AIM: To evaluate the expression pattern of E-cadherin/catenin complex in gastric carcinoma and analyze their association with tumor clinicopathological features and patient survival. MATERIAL AND METHODS: Inmunohistochemical staining of E-cadherin, alpha and ss-catenin was performed from paraffin specimens of 65 gastric carcinomas. RESULTS: Abnormal expression of E-cadherin, alpha and ss-catenin was demonstrated in 82%, 85% and 88% of gastric carcinomas, respectively. There was a significant correlation between abnormal expression and Lauren pathological classification and depth of infiltration, but not with tumor stage, positive lymph node metastases and survival. CONCLUSION: Abnormal expression of E-cadherin, alpha and ss-catenin occurs frequently in gastric carcinoma and correlates with histological grade.

Cadherins↗
PubMed2006

Preneoplastic lesions in gallbladder cancer.

BACKGROUND: Gallbladder cancer is an uncommon disease except in countries like Chile and areas of India and Japan. The knowledge regarding the etiology and mechanisms through which this neoplasia is developed is significantly less compared to other malignant tumors. RESULTS: The epithelial lesions involved in gallbladder carcinogenesis are dysplasia and adenomas that represent two biologically distinct carcinogenetic models. Dysplasia progresses to carcinoma in situ (CIS) and subsequently becomes invasive. Over 80% of invasive gallbladder cancers present areas adjacent to the CIS and epithelial dysplasia. Other authors have demonstrated adenomatous areas in carcinomas, or malignant transformation in an adenoma. The low incidence of gallbladder adenomas (0.14% of cholecystectomies) and the presence of adenomatous remnants in the neighboring mucosa to early carcinomas in less than 3% of the cases suggest the limited importance of this carcinogenic pathway. Epithelial dysplasia which is not associated with gallbladder cancer is observed in approximately 1% of cholecystectomies for symptomatic lithiasis. Metaplasia, dysplasia, and CIS are present in the mucosa adjacent to the cancer in 66%, 81.3%, and 69%, respectively. The average ages of patients with dysplasia not associated to cancer (51.9 years), early carcinomas (56.8 years), and advanced carcinomas (62.9 years) demonstrate a gradient which suggests the progression of these lesions. CONCLUSIONS: From the morphological point of view, the dysplasia-carcinoma sequence is the most plausible carcinogenic pathway for gallbladder cancer, a process which would require a period of approximately 10 years.

Adenocarcinoma↗
PubMed2006

Gallstones and gallbladder cancer-volume and weight of gallstones are associated with gallbladder cancer: a case-control study.

BACKGROUND: Gallstones are considered the most important risk factor for gallbladder cancer. AIM: To identify differences in the number, weight, volume, and density of gallstones associated with chronic cholecystitis (CC), gallbladder dysplasia (GD), and gallbladder cancer (GBC). METHODS: A total of 125 cases were selected, of which 93 had gallstones associated with GBC and 31 had gallstones associated with GD. The controls were those with CC, matched by sex and age. The number, weight, volume, and density of these gallstones were examined in order to determine differences and relative cancer risk. RESULTS: Number: Multiple gallstones were present in over 76% of cases (GBC and GD) and controls (P = ns). The average number of multiple stones was 21 in GBC versus 14 in controls (P < 0.01). Weight: The average weight of the gallstones was 9.6 g in GBC versus 6.0 g in controls (P = 0.0004). The average weight in multiple stones over 10 g had strong association with GBC (P = 0.0006). Volume: The average volume was 11.7 and 6.48 ml in GBC and controls (P = 0.0002). Average volumes of 6, 8, and 10 ml had a relative cancer risk of 5, 7, and 11 times, respectively. Size: No differences were shown between GBC, GD, and controls. CONCLUSIONS: The volume of gallstones associated with other risk factors of GBC may be helpful in prioritizing cholecystectomies in symptomatic patients.

Analysis of Variance↗
PubMed2006

[Frequency of K-ras mutation in biliary and pancreatic tumors].

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.

Adult↗
PubMed2006

Promoter methylation profile in gallbladder cancer.

BACKGROUND: Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time. METHODS: Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained. RESULTS: All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. CONCLUSIONS: The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

Acid Anhydride Hydrolases↗
PubMed2006

Prognostic factors of phyllodes tumor of the breast.

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.

Adult↗
PubMed2005

[Promoter methylation profile in gastric cancer].

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.

Adult↗
PubMed2005

[Detection of human papilloma virus in cytologic samples or biopsies of the cervix].

BACKGROUND: The DNA quality for the detection and typification of Human Papilloma Virus (HPV) varies according to the type of sample in which it is studied. This may affect the sensitivity and specificity of the method employed. AIM: To study the yield and specificity of HPV detection and typification in uterine cervical samples obtained by cervical brushing fresh frozen and formalin fixed tissue. MATERIAL AND METHODS: Cytological, fresh frozen and fixed tissue samples from 44 patients (nine with low grade lesions and 35 with high grade lesions) were studied. Nested polymerase chain reaction for genes E6/E7 was used to typify HPV groups as low risk or high risk. RESULTS: Of all the cytological samples obtained by brushing 84% of fixed samples and 43% of fresh frozen samples were positive for HPV. The yields were significantly different when comparing brushing with fixed tissue or fresh frozen tissue and fixed tissue with fresh frozen tissue (p <0.05). The frequency of high risk HPV fluctuated from 41% in fresh frozen tissue to 98% in cytological samples. Low risk HPV was detected in 16% of fresh frozen tissue and 68% of cytological samples. A mixed infection was detected in 66%, 41% and 14% of cytological, fresh frozen and fixed tissue samples respectively. CONCLUSIONS: Cytological samples obtained by brushing had the highest yield for the detection of cervical infection with HPV.

Biopsy↗
PubMed2005

Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder.

BACKGROUND: Gallbladder cancer is very common in Chile and is the leading cause of cancer deaths in women aged over 40 years. However, there is limited information about the molecular changes involved in its pathogenesis. Microsatellite analysis was performed using polymerase chain reaction (PCR)-based assays to identify genetic loci that were altered in neoplastic and preneoplastic conditions of early and advanced gallbladder cancer. Our findings were then correlated with clinicopathological variables and survival time. METHODS: We selected 59 surgical specimens of gallbladder adenocarcinomas (29 early cancers and 30 advanced cancers) and 22 surgical specimens from patients with chronic cholecystitis from a high-risk area for gallbladder cancer (Temuco, Chile). Laser capture microdissection (LCM) was used to harvest tumor cells and preneoplastic lesions. Microsatellite analysis was performed using 13 different markers. The tumors and preneoplastic lesions were also examined with immunohistochemistry for hMLH1, hMSH2, and hMSH6. RESULTS: We found that 10% (6/59) of gallbladder cancers showed high-frequency microsatellite instability (MSI-H), with identical proportions in both early and advanced cancers. In premalignant lesions adjacent to the six MSI-H tumors, we detected instability in two of six examples of intestinal metaplasia (33%) and five of six examples of dysplasia (83%). All MSI-H cases showed an altered pattern with the antibodies studied. MSI status was not associated with survival or other clinicopathological features. No MSI or immunohistochemical alterations were found in the chronic cholecystitis group. CONCLUSIONS: Microsatellite instability was observed in equal proportions in early and late cancers, and it was also found in premalignant lesions, indicating that inactivation of mismatch repair genes occurs early in gallbladder carcinogenesis.

Adenocarcinoma↗
PubMed2004

[Neoadjuvant chemoradiotherapy in gallbladder cancer].

BACKGROUND: Gallbladder cancer is generally associated with a poor prognosis, being local recurrence the main pattern of failure. AIM: To evaluate neoadjuvant chemoradiation as a means to improve the prognosis in gallbladder cancer. PATIENTS AND METHODS: Twenty three gallbladder cancer patients were prospectively treated between June 1993 and September 1999 in the Temuco Regional Hospital. Eighteen (82%) patients had subserosal infiltration, while three (13%) had serosal and two (9%) adipose tissue infiltration. Chemotherapy was done with 5-fluorouracil in continuous infusion during 5 days at day 1 and 28 of treatment. Radiotherapy consisted in a total dose of 4500 cGy, divided in 25 sessions. Patients' survival was compared with a series of 19 patients not subjected to chemoradiation, formerly treated at the institution. RESULTS: Twenty patients had hematological problems secondary to the therapy. Leucopenia and thrombocytopenia were the most common toxic effects and eight had leucopenia under 2.0 x 10(3) during the treatment course. Chemoradiation delayed surgical treatment in eight patients. After the chemoradiation protocol, seven patients were excluded from surgical treatment and 14 patients underwent resection. Three of the latter (11%) had liver involvement and four (14%) had lymph node involvement. Among the patients who underwent resection, five are still alive with a follow up of 43.8 months. Treated patients had a worst actuarial survival than subjects not treated with chemoradiation. CONCLUSIONS: In this series of patients chemoradiation had no positive effect and a potentially detrimental effect in patients with gallbladder cancer.

Adult↗
PubMed2004

[Management of gallbladder cancer with invasion of the muscular layer].

BACKGROUND: Gallbladder cancer is the leading cause of death of cancer among women in Chile. Detection of early forms of the disease during the pathological study of the cholecystectomy specimen is common. The management of these cases, specially those with invasion of the muscular layer is under discussion. AIM: To analyze the clinical features of patients with gallbladder cancer and muscular layer invasion and their prognosis after a simple cholecystectomy. PATIENTS AND METHODS: We studied a series of 46 patients with gallbladder cancer and invasion of the muscular layer. In the majority of cases diagnosis was performed at the moment of specimen study. Eleven patients underwent reoperation. Of these, ten underwent lymphadenectomy and liver resection while one patient underwent resection of the cystic duct stump. RESULTS: During follow up, five patients died as a consequence of gallbladder cancer. Overall survival was 78%, with no differences between patients subjected or not a new operation. CONCLUSIONS: Gallbladder cancer with muscular infiltration has a good prognosis, independent of the type of therapy.

Adult↗
PubMed2004

[Clinicopathological features of gallbladder polyps and adenomas].

BACKGROUND: Chile has a high frequency of gallbladder cancer. Polyps are common lesions of gallbladder mucosa but there is little information about their morphological features. AIM: To report the clinical and pathological features of 219 gallbladder polyps. MATERIAL AND METHODS: Cholecystectomites samples in which a polypoid lesion was diagnosed microscopically. In all cases, complete clinical information and digitalized images of the complete surgical specimens was reviewed. RESULTS: In a period of 10 years, 21,412 gall-bladders were processed. Among these, 884 carcinomas were diagnosed and in 219 cases (1%) a polyp was found. One hundred and eighty three patients were females (mean age 49.3 years) and 36 males (mean age 53.4 years). The preoperative diagnosis of gallbladder polyp wars done only in 26 cases (12%). Eighty five percent of polyps were non-neoplastic (metaplastic in 32%, cholesterol in 29%, hyperplastic in 22% and inflammatory in 2%). The remaining 15% were adenomas. Seventy five percent of non-neoplastic polyps were located in the proximal half of the gallbladder and 88% of adenomas in the distal half. Ninety five percent of non-neoplastic polyps measured less than 10 mm. Among adenomas, 47% measured less than 5 mm and 28% more than 10 mm. Smaller polyps were of cholesterol and larger polyps were adenomas. Eight adenomas were associated with an adenocarcinoma, two had less than 5 mm length. Mean age of patients with adenomas associated to cancer was higher than patients with pure adenomas (64.6 and 44.3 years respectively, p > 0.001). CONCLUSIONS: There are size and location differences between non neoplastic polyps and adenomas. Adenomas associated to cancer may measure less than 5 mm. Therefore the polyp size criteria to decide surgical behavior in symptomatic gallstone patients may be misleading.

Adenocarcinoma↗
PubMed2004

[DNA content and survival in subserous gallbladder carcinoma].

BACKGROUND: The clinical and morphological characterization of the subserous gallbladder carcinomas is controversial. AIM: To study the prognostic importance of DNA content of subserous gallbladder carcinoma. MATERIAL AND METHODS: We studied 104 females aged 60+/-12 years old and 16 men aged 70+/-13 years old. In all of them diagnosis was established after mapping of cholecystectomy sample and had a complete clinical follow up. DNA content was measured by flow cytometry. RESULTS: All tumors were adenocarcinoma, and only 16% were well differentiated. Aneuploidy was observed in 29 cases (26%) with DNA index fluctuating between 1.1 and 1.8. Lymphatic vessel tumor involvement was present in 16 of 22 cases with aneuploidy and in 22 of 46 diploid tumors (p=0.05). Eighty nine percent of aneuploid tumors were detected macroscopically and 11% were unapparent. Five years survival was non significantly better among patients with diploid tumors than in patients with aneuploid tumors (45 and 28%, respectively, p=0.2). The histological differentiation was the only variable significantly associated with survival. CONCLUSIONS: Aneuploidy is present in 26% of subserous gallbladder carcinoma. It is not related with any of the morphological or clinical variables studied in this series of patients.

Adenocarcinoma↗
PubMed2004

[K-ras gene mutation in gallbladder carcinoma].

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.

Adenocarcinoma↗
PubMed2004

[Promoter methylation profile in breast cancer].

BACKGROUND: Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms. AIM: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior. MATERIAL AND METHODS: Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT. RESULTS: We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHT were 41.4%, 11.4%, 52.9%, 70% and 42.9%, respectively. We found a relationship between CDKN2A methylatlon 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 larger tumor size (p<0.05), FHIT methylatton and lack of estrogen rectptor IHC expression (p<0.05). CONCLUSIONS: The high frequency of promoter methylation in patients with breast cancer confirms its role in breast 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 of new criteria for clinical and therapeutic decision making.

Acid Anhydride Hydrolases↗
PubMed2004

[Inactivation of CDKN2A gene (p16) in gallbladder carcinoma].

BACKGROUND: The CDKN2A gene encodes a cyclin dependent kinase inhibitor, p16, which promotes cell cycle arrest. Methylation of the promoter region transcriptionally inactivates the gene. AIM: To study the relationship between methylation status of the prometer region of p16 gene, the immunohistochemical expression of p16 and clinical and morphological features of gallbladder carcinoma. MATERIAL AND METHODS: We analyzed the methylation status of the promoter region of the CDKN2A gene in gallbladder adenocarcinomas using methylation specific PCR (MSP). We also used microsatellite markers near the CDKN2A gene to detect allelic imbalance (AI) and examined the tumors by immunohistochemistry (IHC) for p16 expression. RESULTS: Of 38 gallbladder adenocarcinomas analyzed by IHC, 11 cases (29%) were negative for p16 protein. Nine (24%) had methylation of the promoter region of the CDKN2A gene. Twenty nine cases were negative for methylation, but four (14%) of these 29 exhibited AI at one or more of the microsatellite markers. CDKN2A promoter methylation was not associated with microsatellite instability (MSI-H). CONCLUSIONS: The inactivation of CDKN2A by methylation and/or deletion might play an important role in gallbladder carcinogenesis.

Adult↗
PubMed2004

[Detection of bone marrow micrometastases in patients with gallbladder cancer].

BACKGROUND: There is a very strong documented correlation between the appearance of cancer cells in blood and occurrence of metastasis in gastrointestinal cancer. AIM: To determine MUC1, CK19, CK20 and CEA mRNA expression in bone marrow of patients with gallbladder cancer and evaluate its clinical significance. MATERIAL AND METHODS: Sixty eight samples were analyzed, 38 bone marrow samples of gallbladder cancer patients, 20 healthy donors, and 10 frozen samples of gallbladder cancer. Nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) was used to analyze mRNA expression. RESULTS: All frozen tumors were positive for CEA, CK19, and MUC1 mRNA and 70% were positive for CK20. Seventeen of 20 donor samples were positive for MUC1 and only one sample from donors was positive for both CK20 and CK19 mRNA. Among the 38 blood and bone marrow samples of gallbladder cancer patients, the expression of MUC1, CK19, CK20, and CEA, mRNA was 60.5% (23/38), 31.6% (12/38), 7.9% (3/38), and 7.9% (3/38), respectively. Disregarding the MUC1 results. 37% (14/38), 13% (5/38) and 5% (2/38) were positive for one, two and three markers respectively. Not significant differences were found in survival with a follow up to 12 months. CONCLUSION: Our results indicate that the molecular detection of tumor cells in bone marrow in patients with gallbladder carcinoma is technically possible, being CEA, CK19 and CK20 gene expression the best markers. The MUC1 gene expression marker was highly unspecific and it should not been considered. The detection of bone marrow micrometastasis might be helpful in prognosis and the selection of clinical treatment but a larger series with a longer follow-up should be studied.

Adult↗