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I Roa

Publications and source records attributed to I Roa.

At least 19 recordsLinked to original sources
PubMed1997

p53 tumour suppressor gene protein expression in early and advanced gallbladder carcinoma.

AIMS: Gallbladder carcinoma is one of the most frequent malignant tumours occurring in Chile and the mortality rate in both sexes ranks among one of the highest in the world. Mutation of p53 tumour suppressor gene has been demonstrated in many tumours. Our aim was to determine protein expression of p53 gene in early and advanced gallbladder carcinoma. METHODS AND RESULTS: Protein expression of gene p53 was studied by immunohistochemical means in 191 gallbladder carcinomas (157 primary tumours, 34 metastases) and 25 controls. In 86 out of 191 cases (45%), protein expression of gene p53 was observed. Differences related to sex, age, or race were not observed. All gallbladder controls were negative. Twenty-five per cent of well-differentiated tumours were p53 positive, while moderate or poorly differentiated carcinomas reached 50% (P = 0.04). p53 expression was observed in 23.5% of early carcinomas and in 48.2% of advanced carcinomas (P = 0.01). No differences between primary tumours and metastasis were demonstrated. CONCLUSIONS: Protein expression of p53 tumour suppressor gene is observed in 45% of gallbladder carcinomas. The absence of expression in controls and in normal mucosa adjacent to tumours suggests its utility in differentiating atypical gallbladder epithelia from neoplastic lesions.

Carcinoma↗
PubMed1997

DNA ploidy pattern and tumor suppressor gene p53 expression in gallbladder carcinoma.

The relationship between p53 gene expression and DNA content in advanced gallbladder carcinoma was studied. Fifty-three cases of advanced gallbladder carcinoma (45 primary tumors and 8 metastases) were analyzed, p53 protein expression was determined by immunohistochemistry, DNA content was measured by cytophotometric techniques. Study subjects included 45 (85%) female and 8 male patients, with an overall mean age of 58.6 years. Positive staining for p53 protein was observed in 27 (51%) cases. In subserosal tumors, the expression was significantly less than that in tumors that reached the serosa (P = 0.01). Twenty-nine (55%) cases were diploid and 24 were aneuploid. Sixty-seven % of primary tumors were diploid, whereas 87% of metastases showed an aneuploid DNA content. Both diploid and aneuploid tumors were positive for the p53 protein in the same proportion, and p53 was also expressed equally in both primary and secondary tumors. In advanced gallbladder carcinoma, the expression of the p53 gene was earlier than the accumulation of abnormal quantities of chromosomal DNA in the tumor cells. The determination of these events as markers in preneoplastic lesions is warranted in gallbladder carcinogenesis.

Adenocarcinoma↗
PubMed1996

Comparison of mutagenic activity of bile between Chilean and Japanese female patients having cholelithiasis.

The mutagenic activity of bile was compared between Chilean and Japanese female patients having cholelithiasis by the Ames assay using Salmonella typhimurium tester strain TA98 in the presence of S9 mix with blue rayon adsorption technique. A reason for conducting the present investigation is that Chile and Japan have the highest mortality rates for the gallbladder cancer (GBC) in the world. Of 24 bile samples collected in Chile, 20 (83.3%) samples showed mutagenicity. In the case of Japanese bile, 21 (80.8%) of 26 and 5 (19.2%) of 26 cases were mutagenic in samples from high- and low-risk areas for GBC, respectively. Therefore, both the Chilean and the Japanese samples collected in high-risk areas showed higher mutagenic rates than the Japanese ones in a low-risk area, with a statistical significance (p < 0.001), chi-square test). The average number of revertant colonies were 128 +/- 92 (mean +/- SD), 62 +/- 14 and 66 +/- 13, respectively, when the blue rayon extracts of 200 microliters bile were applied to the Ames test. Thus, Chilean bile had a tendency to show a higher mutagenic activity than Japanese.

Adult↗
PubMed1996

p53 protein overexpression in gallbladder carcinoma and its precursor lesions: an immunohistochemical study.

Gallbladder carcinoma is one of the most frequent neoplasms diagnosed in Chile. Although the premalignant lesions have been extensively studied and are well characterized, there is only limited information about the genetic abnormalities that might be important in the pathogenesis of gallbladder carcinoma or that might have prognostic implications. The present study evaluates the immunohistochemical expression of p53 protein in premalignant lesions and invasive carcinoma of the gallbladder, and correlates the p53 expression with histological type, grade of differentiation, and level of invasion of the tumor. The authors studied the immunohistochemical p53 protein overexpression in 52 gallbladder carcinomas, 47 carcinomas in situ (CISs), 34 dysplasias, and 10 specimens with chronic cholecystitis containing normal and metaplastic epithelium. A semiquantitative scoring system was used to assess the p53 reactivity. p53 overexpression was found in 34 of 52 (65.4%) carcinomas, 21 of 47 (44.7%) CISs, and 11 of 34 (32.4%) dysplasias. There were no significant differences in p53 expression in premalignant lesions associated with invasive carcinoma and those that were not. Normal and metaplastic epithelium did not overexpress p53 protein. In adenocarcinomas, no correlation was found between p53 protein overexpression and histological subtype, grade of differentiation, or level of invasion. The high incidence of p53 overexpression in gallbladder carcinoma and its presence in dysplasia, even in specimens without invasive carcinomas, suggests that this abnormality is an important and early event in the pathogenesis of the tumor. The progressively increasing incidence of p53 overexpression observed from premalignant lesions to invasive tumor provides additional support to the view that this is the usual route for the development of infiltrating gallbladder carcinoma.

Carcinoma↗
PubMed1996

Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression.

BACKGROUND & AIMS: Scarce biological information exists about the importance of preneoplastic lesions in gallbladder cancer. The aim of this study was to estimate the time required for the sequence of dysplasia (DY) to carcinoma of the gallbladder. METHODS: Eighty-four cases of DY, 60 cases of early carcinomas (ECs), 181 cases of advanced carcinomas (ACs), and 121 cases of metastatic (ME) gallbladder cancer were analyzed. Age was used as the main parameter. Statistical analysis was performed using analysis of variance and multiple regression analysis. RESULTS: Among all cases, the mean age of female patients was lower than the mean age of male patients (P = 0.001). A significant difference in mean age between sexes by specific type of lesion was also observed (P < 0.001). The mean age was 46.3 years (SD, 16) in the DY group, 57.5 years (SD, 16.7) in the EC group, 59 (SD, 13.7) in the AC group, and 61.1 (SD, 12.1) in the ME group. Multiple regression analysis showed statistically significant differences (r = 0.386; P < 0.001) in the mean age of patients with dysplastic lesions compared with the carcinoma group. CONCLUSIONS: According to these observations, the period required to progress from dysplasia to advanced gallbladder carcinoma would be around 15 years, observing a continuum in the progression of the lesions.

Adult↗
PubMed1996

[CAA 19-9 and carcinoembryonic antigen in gallbladder cancer].

The aim of this work was to assess the diagnostic yield of serum tumoral markers, Ca 19-9 and carcinoembryonic antigen, in patients with gallbladder cancer. We studied 54 patients of whom 33 had gallbladder cancer and in 21 the tumor was removed previously and were presently free of disease. Twenty one patients with cholelithiasis were used as controls. Ca 19-9 was over 37 U/ml in 22 (65%) patients with cancer, in two patients free of disease and in two controls. The sensitivity and specificity of Ca 19-9 was 0.66 and 0.90 respectively. Carcinoembryonic antigen was over 2.5 ng/ml in 25 patients with cancer (56%) and its sensitivity and specificity was 0.75 and 0.71 respectively. Using a cutoff point of 4 ng/ml, these figures were 0.51 and 0.9 respectively. The better predictive capacity was given by a Ca 19-9 over 37 U/ml or a carcinoembryonic antigen over 4 ng/ml. It is concluded that, although the sensitivity and specificity of these markers was adequate in this work, one must bear in mind that studied patients had advanced tumors.

Adult↗
PubMed1996

[Gallbladder cancer: a review].

In Chile, gallbladder cancer is the tumor with the highest mortality rates among women. Cholelithiasis is the most common associated factor and the reduction in cholecystectomy rates could be an important factor in the incidence of gallbladder cancer. Unfortunately, the disease is diagnosed late and the study of the surgical piece is the main form of early recognition. The degree of gallbladder wall infiltration by the tumor is the simplest and best staging method that has prognostic value. Gallbladder fat must be considered as a separate tissue, since its biological behavior differs from that of the subserous. The treatment of these tumors is based in their dissemination modality that is mainly local and regional. Surgical resection and radiotherapy are potentially effective. However the detection of high risk patients that should be subjected to cholecystectomy should be the better therapeutic alternative.

Female↗
PubMed1996

[Hepatocellular carcinoma. General aspects of diagnosis and treatment].

Hepatocellular carcinoma is the most frequent form of primary hepatic cancer and has a high dissemination capacity. About 90% of tumors develop over a pre-existing cirrhosis but they also may occur in a normal liver. It has a higher frequency among males and 80% of tumors have clinical manifestations. It is associated to hepatitis B and C virus infection, alcoholism, cirrhosis of any etiology, consumption of aflatoxin Bl, oriental race and familial history. Patients are staged using classifications proposed by Okuda, Child-Pugh and the performance status test. Alpha feto protein is useful for diagnosis and follow up Abdominal ultrasound, hepatic scintiscan, angiography with lipiodol, CAT scan and nuclear magnetic resonance have a high diagnostic yield. Non surgical therapeutic alternatives include intratumoral alcoholization, chemoembolization and other such as tamoxifen and monoclonal antibodies. Surgical treatment is based on hepatic resection, whose magnitude depends on hepatic function. Hepatic transplantation is a new therapeutic alternative for patients in whom resection is not feasible and have a single small tumor without metastases.

Biomarkers, Tumor↗
PubMed1995

Allele-specific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile.

Although gallbladder carcinoma is one of the most frequent neoplasms in Chile, there is limited information about the molecular changes involved in its pathogenesis. We investigated the incidence of ras gene mutations and loss of heterozygosity (LOH) at the following genes/loci: p53, DCC, rb, 5q 3p, 8p, and 9p. We precisely microdissected 194 relevant areas from paraffin-embedded microslides from 25 gallbladder carcinomas and their accompanying nonneoplastic lesions (which were present in 15 cases) from patients in Chile. The specimens were analyzed by PCR-based assays for LOH, and we designed a RFLP method for ras mutations and immunohistochemistry for p53 protein overexpression. We determined that LOH at p53 (91%), 9p (50%), 8p (44%) and DCC (31%) are frequent events and that LOH at p53, 9p, and DCC are early events, while ras mutations and LOH at 3p, rb, and 5q occurred occasionally. LOH at p53 occurred more frequently and earlier than protein overexpression. The mean number of mutations present in invasive carcinomas was 2.1, and in six cases, LOH at the p53 gene was the sole mutation detected. The same allele was lost in 61 (93%) of 71 nonneoplastic foci as in the corresponding invasive carcinomas for all four mutations studied. The odds of this occurring by chance are approximately 4 x 10(-15). Although clonality cannot be excluded, allelic loss appears to be highly directed, but the mechanism for allele-specific mutations remains to be determined.

Adenocarcinoma↗
PubMed1995

[Gallbladder cancer. Case-control study].

Gallbladder cancer is the principal oncological cause of death in chilean women and cholelithiasis is a well recognized risk factor. Aiming to unravel other risk factors for gallbladder cancer, we compared 50 patients subjected to cholecystectomy in whom a gallbladder cancer was found with 50 age and sex matched operated controls without cancer. Subjects were clinically assessed and interrogated about demographic, obstetrical features and feeding features. Multiples and early pregnancies were factors significantly associated to the development of gallbladder cancer. Twenty subjects (44%) with cancer knew that they had cholelithiasis and 41 patients in each group were symptomatic. It is concluded that pregnancy may be a risk factor for gallbladder cancer probably due to the lithogenic effect of its hormonal changes. Also, early cholecystectomy in symptomatic individuals may be an effective preventive measure.

Adult↗
PubMed1995

[Proliferating cell nuclear antigen in cervical cancer and precursor lesions].

The aim of this study was to study the degree of cellular proliferation quantifying the immunohistochemical expression of the proliferating cell nuclear antigen. We assessed paraffin embedded samples of 25 infiltrating epidermoid cervical carcinomas, 76 precursor lesions (34 of low and 42 of high grade), 29 normal and 13 metaplastic epidermoid epithelia. Mean values of proliferating cell nuclear antigen expression were 13.7% in normal epithelia, 15.7% in epidermoid metaplasia, 37.1% in low grade precursor lesions (35.3% in condilomas and 38.8% in mild dysplasia), 48.7% in high grade lesions (47.9% in moderate dysplasias, 50.5% in severe dysplasias and 50% in carcinoma in situ) and 54.7% in infiltrating carcinoma. There were differences in proliferating cell nuclear antigen expression nd mitotic index between low grade precursor lesions and high grade lesions and infiltrating carcinoma. No correlation was observed between mitotic index and proliferating cell nuclear antigen expression. We conclude that infiltrating epidermoid cervical carcinoma and its precursor lesions have a high level of proliferative activity, demonstrated by a high percentage of cells in active phases of the cellular cycle.

Carcinoma, Squamous Cell↗
PubMed1995

[Gallbladder cancer: immunohistochemical expression of the protein related to estrogen receptor (p29) and of the protein induced by estrogen (pS2)].

The high frequency of gallbladder cancer in women suggests a role for estrogens in its development. The aim of this study was to study the immunohistochemical expression of p29 estrogen receptor associated protein and pS2 estrogen induced protein in 111 pathological samples of gallbladder carcinoma, coming from 88 women and 23 men, 30 metastases of gallbladder cancer, coming from 25 women and 5 men and in 25 non-tumoral gallbladders. In the latter, p29 protein was positive in 12 samples (48%) and pS2 in 15 cases (60%). p29 was positive in 40% and pS2 in 32% of tumors. p29 expressed with higher frequency in metastases than in primary tumors (57 and 31% respectively, p < 0.02). Early tumors had a significantly lower expression of p29 than advanced tumors or than metastases. Both proteins expressed in 18% of samples (synchronic expression) whereas one of both proteins did so in 60% of cases (asynchronic expression). We conclude that most gallbladder cancer samples express proteins associated to estrogen receptor or induced by estrogens.

Adenocarcinoma↗
PubMed1994

[Laparoscopic cholecystectomy makes difficult the analysis of gallbladder mucosa. Morphometric study].

Laparoscopic gallbladder surgery damages gallbladder mucosa, impeding an adequate histological examination. We studied gallbladder samples coming from 56 conventional and 44 laparoscopic cholecystectomies performed in patients with chronic cholecystitis without signs of acute inflammation. The length of each examined sample and the length of the portion where superficial epithelia was not found was measured. No differences in sample length was found between both types of cholecystectomy. However; the segment with superficial mucosa was significantly shorter in the samples coming from laparoscopic surgery. Seventeen samples did not contain mucosa at all and 14 of these (82%) came from laparoscopic procedures. Eighty six percent of samples coming from laparoscopic surgery were considered inadequate for histological study compared to 36% of samples coming from conventional cholecystectomy. It is concluded that laparoscopic cholecystectomy hampers the study of gallbladder mucosa and may have an impact on the diagnosis of neoplastic gallbladder lesions.

Cholecystectomy↗
PubMed1994

[Immunohistochemical expression of epidermal growth factor receptor (EGFR) in epidermoid carcinoma of the cervix uteri and its precursor lesions].

The epidermal growth factor receptor (EGFR) immunohistochemical expression was determined in 24 histological samples of squamous cell carcinoma of the cervix, 81 cervical squamous intraepithelial lesions (47 low-grade and 34 high grade), 20 normal squamous epithelia, 11 squamous mature metaplasias and 14 cervical adenocarcinomas. In 30 cases, it was determined by means in situ hybridization the presence of Human Papillomaviruses 6/11, 16/18 and 31/33/35. The immunohistochemical EGFR expression was higher in high-grade epithelial lesions (64.7%), particularly moderate dysplasia (72.2%), than in low-grade lesions (44.7%) and squamous carcinoma (45.8%), with significance differences only between high-grade lesions and normal squamous epithelia (p < 0.02). There were not EGFR expression differences between cervical squamous carcinoma (45.8%) and adenocarcinoma (42.9%). These findings suggest that the elevated expression of EGFR may be linked, at least initially, to the malignant state of the cervical squamous epithelia. On the other hand, the higher presence of HPV 16/18 than other HPV types in EGFR positive lesions, indicates some association between both factors.

Adenocarcinoma↗
PubMed1994

[Proliferating cell nuclear antigen (PCNA) in patients with malabsorption syndrome: comparative study with morphometric parameters].

The study of small bowel mucosa is routine in the study of patients with malabsorption. We report 16 children aged from 8 months to 6 years old (2 with giardiasis, 8 with primary malnutrition and 5 with celiac disease) in whom a morphometric and PCNA immunostaining was performed in the small intestinal biopsy. Positivity for PCNA was found in the lower portion of the crypts reaching 156 microns of heigh in patients with giardiasis, 103 microns in primary malnutrition and 182 microns in celiac disease (p < 0.01 compared to primary malnutrition). A negative and significant correlation was found between the degree of architectural disorder (expressed the mucosal index) and the proliferative portion of the crypts (expressed as the percentage of PCNA(+) crypts. We propose these methods as complements to the small bowel mucosa histopathological study in the diagnosis of celiac disease, to assess the degree of architectural disorder and the proliferative activity.

Child↗