Mutación puntual del gen supresor de tumores TP53 en lesiones preneoplásicas y neoplásicas del estómago / Mutations of TP53 suppressor gene in pre-neoplastic and neoplastic lesions of the stomach: cross-sectional study in a high risk region

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-Ám 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 percent 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

¿Es el cáncer de la vesícula biliar una enfermedad de mal pronóstico en Chile? / Is galbladder cancer a tumor 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 percent at five years. In 69 percent 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 percent 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

Detección de secuencias del gen BCR-ABL mediante RT-PCR en pacientes con leucemia en la IX Región Chile / Detection of BCR-ABL gene sequences using polymerase chain reaction reverse transcriptase in patients with leukemia from the IX Región of 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

Elementos morfológicos pronósticos en el cáncer de la vesícula biliar / Morphological prognostic factors 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 percent at ten years. Sex or ethnic origin did not influence survival. Early tumors had a 92 percent survival at 10 years whereas the survival of advanced tumors was 16 percent at 5 years. Subserous tumors had a 5 years survival of 32 percent whereas serous tumors had a 5 years survival of 11 percent. 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

Carcinoma incipiente de la vesícula biliar: estudio clínico patológico y pronóstico de 196 casos / Clinical and pathological features of early gallbladder carcinoma

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 per cent were well differentiated and 32 per cent moderately differentiated. Tumors were not visible macroscopically in 132 cases. Five and 10 years survival was 92 per cent. Subjects of less than 40 years old had a 100 per cent 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 per cent of gallbladder carcinomas can be classified as early and its diagnosis requires a directed study. Simple cholecystectomy is curative for this type of gallbladder cancer

Hallazgos en reintervenciones quirúrgicas por cáncer de la vesícula biliar en pacientes con y sin quimio-radiación preoperatoria / Pathological findings in surgical reinterventions for gallbladder cancer in patients with and without preoperative chemo and radiotherapy

Background: The usefulness of surgery in the treatment of gallbladder cancer has not been clearly established. The benefits of chemo and radiotherapy are similarly dubious. Aim: To report the pathological findings in patients subjected to surgical reinterventions for gallbladder cancer. Patients and methods: We report 54 patients with gallbladder cancer that were subjected to a second surgical intervention for resection of liver segments IVb and V and lymph nodes corresponding to the liver hilar, portal, peripancreatic, celiac artery and periaortic territories. Thirteen of these patients were subjected to preoperative chemo-radiotherapy (4500 Gy and 5-fluouracil 500 mg/m2). Results: Lymph node metastases were found in 25 and 38 percent, and liver metastases in 25 and 28 percent of patients with or without chemo-radiotherapy respectively. The most frequent pathological findings attributed to radiation in the liver were fatty infiltration in 75 percent of cases, vascular transformation in 83 percent of cases and minimal periportal lymphocyte infiltration in 40 percent of cases. Lymph nodes were atrophic in 67 percent of cases and had foci of cortical necrosis in 46 percent of cases. Three cases had regional lymph node and liver metastases. Most tumor cells were viable. Conclusions: No differences in the number of lymph node or liver metastases were observed between patients with and without chemo-radiotherapy. No effect of the treatment on residual tumor was observed either

Expresión de CD44 HCAM en el carcinoma subseroso de la vesícula biliar / CD44 HCAM expression in subserous gallbladder carcinoma

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 percent were well differentiated. CD44 was expressed in all controls and in 91 percent, the expression was normal. In 57 percent of cancer samples, CD44 expression was abnormal, in 50 percent it was less expressed and in 24 percent, 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 percent. 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 percent of subserous gallbladder carcinomas show an abnormal CD44 expression

Gen supresor de tumores p53 en neoplasias digestivas / p53 tumor supresor gene in digestive cancer

Malignant diseases of the digestive tract cause more than 50 percent of deaths due to cancer in Chile. There is a high incidence of gastric and gallbladder cancer and an increasing frequency of colorectal cancer. P53 tumor suppressor gene has a great importance in carcinogenesis and its alterations are specially important in digestive tract tumors such as colorectal cancer. There is contradictory evidence about the frequency of p53 gene or protein alterations or their biological significance. There is little information about p53 in Chile and it is mostly limited to immunohistochemical studies. This revision analyzes the frequency of p53 alterations in digestive tract tumors in Chile, using immunohistochemical and molecular biology methods. A special emphasis is given to the prognostic importance of this gene

Mutación del gen p53 en el cáncer de colon y recto / P53 gene mutation in colorectal cancer

Background: Genetic events associated to colorectal carcinoma are well characterized, but there is scanty information about this issue in Chilean subjects. Aim: To determine the frequency and distribution of exons 5, 6, 7, 8 and 9 mutations and the immunohistochemical expression of p53 gene in biopsy samples of colorectal carcinoma. Material and methods: p53 gene exons 5, 6, 7, 8 and 9 were directly sequenced in 42 biopsy samples of colorectal carcinoma. Immunohistochemical expression of p53 was determined in 35 samples. Results: Thirty one discrete mutations (12 transitions, 11 transversions and 8 insertions) were observed in 21 samples (60 percent). Nine samples had mutations in exon 5, twelve samples had mutations in exon 6, seven samples had mutations in exon 7 and three samples had mutations in exons 8 and 9. Immunohistochemical expression of p53 protein was observed in 18 of 35 cases. There was a high correlation between the genetic alteration and immunohistochemistry, when p53 was expressed in more the 20 percent of cells. The positive and negative predictive values of p53 expression were 87 and 80 percent respectively. There was a non significant lower mortality among patients with mutations in their biopsies. Conclusions: These results confirm the involvement of p53 gene mutations in colonic carcinogenesis. Immunohistochemical methods for the detection of p53 protein have a high predictive value

Cáncer de mama: contenido de ADN como factor pronóstico / Breast cancer: DNA content as prognostic factor

El estudio y caracterización biológica en el cáncer de la mama permitir adoptar terapéuticas acordes con el grado de agresividad biológica. La utilidad de la determinación del contenido de ADN en el cáncer de mama ha demostrado resultados contradictorios. Se determinó el contenido de ADN de 100 carcinomas de la mama mediante citofotometría y su relación con: tipo histológico, atipia, grado tumoral, mitosis y presencia de metástasis. El promedio de edad del grupo fue de 57,1 años (26-86 años). En 77 casos (77 por ciento) se realizó mastectomía. El tamaño promedio de los tumores fue 3,5 cm (DSñ 2,0 cm). El carcinoma ductal infiltrante fue el más frecuente en 95 casos (95 por ciento). En 37 de los 84 casos (44 por ciento) con linfoadenectomía axilar se encontró metástasis. En el 60 por ciento de los casos se observó contenido aneuploide de ADN. El índice promedio de ADN en los tumores aneuploides fue de 1,2 (DSñ 0,29). No se observaron diferencias entre los tumores diploides y aneploides respecto de la edad, raza, procedimiento quirúrgico ni tamaño tumoral. La frecuencia de aneuploidia fue mayor en relación al grado de atipia (grado I 28,6 por ciento, grado III 68 por ciento), mitosis (I 55 por ciento, III 60 por ciento) y grado tumoral (grado I 65 por ciento, grado III 70 por ciento), sin embargo, estas diferencias no fueron significativas. En los tumores diploides de ADN se observó un 29 por ciento de metástasis linfática, en cambio, en los tumores aneuploides un 55 por ciento (p= 0,02). Nuestro estudio demuestra la relación existente entre contenido de ADN y la presencia de metástasis linfáticas en el cáncer de mama y su potencial uso como factor pronóstico

Mutación del gen p53 en el cáncer de la vesícula biliar / P53 gene mutation in gallbladder cancer

Background: Gallbladder cancer frequency and mortality renders it one of the most important neoplastic diseases in Chile. P53 tumor suppressor gene has been studied in most types of cancer, but there is scarce information about it in gallbladder cancer. Aim: To study the frequency of P53 gene mutation in gallbladder cancer in the ninth region of Chile. Material and methods: In 25 pathological samples of gallbladder cancer, the direct amplification and sequencing of p53 gene exons 5,6,7,8-8 was possible. Results: Seventeen punctual mutations were observed in 13 cases (52 percent). There were 10 transitions, 5 transversions, one insertion (codon 194) and one deletion (codon 186). Eight cases had mutations in exon 5, six had mutations in exon 6, two had mutations in exon 7 and one had mutations in exons 8-9. In 14 of 25 cases, gene p53 protein was positive. When immunohistochemical expression of gene p53 protein was positive in more than 20 percent of cells, there was a high correlation between genetic alterations and immunohistochemical expression of the protein, with a specificity, sensitivity, positive and negative predictive values over 80 percent. Conclusions: P53 gene mutation is observed in a high proportion of gallbladder cancers at it can be accurately detected with conventional immunohistochemical techniques. The importance of this gene in the genesis of this carcinoma should be determined studying preneoplastic lesions and early carcinomas

Helicobacter pylori y gastritis crónica: relación entre infección y actividad inflamatoria en población de alto riesgo de cáncer gástrico / Helicobacter pylori and chronic gastritis: relationship between infection and inflammatory activity in a high risk population for gastric cancer

Background: Helicobacter pylori has been involved in gastric epithelial cell damage and gastric gland loss or atrophy. Aims: to evaluate role of Helicobacter pylori infection in acute and chronic changes of chronic gastritis in a high gastric cancer-risk population. Material and methods: 200 patients with chronic gastritis were selected from pathological files of Temuco Hospital. A complete histopathological protocol was fulfilled considering the presence of infection by Helicobacter pylori-like-organism (HLO), acute and chronic inflammatory infiltrate, epithelial cell damage and epithelial cell regeneration. Results: 82 percent of patients showed infection by HLO. Moreover, this infection reached a frequency of 92.7 percent in gastric ulcer patients and 94.4 percent in duodenal ulcer patients. A statistically significant positive correlation was found between HLO infection and polymorphonuclear infiltrate, Iymphocytic infiltrate, mucus depletion and epithelial regenerative activity. There was not a statistical correlation between HLO infection and atrophy. Finally, 90 percent of patients with multifocal atrophic gastritis and 100 percent of patients with diffuse antral gastritis had HLO infection. Conclusions: HLO gastric infection frequently caused acute inflammatory changes in gastric mucosa with chronic gastritis. Sometimes these changes were severe, with marked polymorphonuclear migration throughout epithelium and severe epithelial cell damage. Recovery of these changes could be considered as a goal in Helicobacter pylori eradication therapy decision

Cáncer gástrico y regulación del crecimiento tumoral: estudio de marcadores de proliferación celular y del complejo proteínas p53/p21WAF1/CIP1/mdm-2 / Gastric cancer and tumor growth regulation: study of cell proliferation markers and protein complex p53/p21WAF1/CIP1/mdm-2

Gastric cancer and tumor growth regulation. Study of cell proliferation markers and protein complex p53/p21WAF1/CIP1/mdm-2. Background: p53/p21WAF1/CIP1 and mdm-2 proteins play an important role in cell cycle regulation. The study of the pathogenesis of gastric cancer is important to understand how these tumors progress during their natural history. Aim: To study the relationship between the immunohistochemical expression of p53/p21WAF1/CIP1 and mdm-2 and cell proliferation in gastric cancer. Material and methods: Fifty one gastrectomy specimens with gastric cancer were studied using immunohistochemistry for p53/p21WAF1/CIP1 and mdm-2. Cell proliferation was determined by immunolabelling with PCNA and Ki67 antigens. Mitosis figures were counted in 10 high power microscopic fields. Results: Patients from whom gastric cancer specimens were obtained had a mean age of 59.3 years. Ki67 and mitosis counting showed the highest correlation index with proliferation indexes studied. No correlation was found between the expression of protein complex p53/p21WAF1/CIP1 and mdm-2 and morphological characteristics of gastric tumors. Mdm-2 protein overexpression was the only marker that showed an independent correlation with cell proliferation. Moreover, mdm-2 positive tumors showed the highest proliferation indexes when p53 was not immunohistochemically over-expressed, as determined by PCNA labelling index. Conclusions: In gastric cancer, a direct correlation between mdm-2 overexpression and cell proliferation was observed. Moreover, the fact that mdm-2 positive tumors showed the highest cell proliferation when p53 was not overexpressed, entitles us to hypothesize that mdm-2 overexpression could play a major role in gastric carcinogenesis

Screening rápido en citodiagnóstico ginecológico / Quick screening in gynecological cytodiagnosis

El screening rápido para citología ginecológica se ha demostrado, como uno de los mejores métodos de control de calidad para el Laboratorio de citología ginecológica, sin embargo, existe escasa información respecto de su utilidad como técnica de screening rutinario. El objetivo de este trabajo es evaluar el screening rápido como método de diagnóstico y compararlo con el método actualmente utilizado. Se sometió a screening rápido de 40 segundo a todas las citologías ginecológicas del Laboratorio por un período de cinco semanas. Se examinaron un total de 4.933 citologías ginecológicas en forma independiente mediante dos métodos (screening rápido y de rutina). Una vez realizados los diagnósticos se procedió a reexaminar el 100 por ciento de las láminas negativas. El screening rápido detectó 378 citologías sospechosas (8 por ciento), de las cuales 130 resultaron finalmente positivas (2,6 por ciento). En 78 casos correspondieron a lesiones de bajo grado, 15 a lesiones de alto grado, 6 casos de carcinomas epidermoide y 31 frotis atípicos. El screening realizado en forma rutinaria detectó 135 casos positivos (2,7 por ciento). Todas las lesiones detectadas en el screening rutinario fueron diagnosticadas en el screening rápido a excepción de 5 casos (4 lesiones de bajo grado y una lesión de alto grado). La revisión del 100 por ciento de láminas negativas demostró 21 casos positivos (falso negativos) (0,4 por ciento), de los cuales 16 eran lesiones de bajo grado, una lesión de alto grado y cuatro frotis atípicos. No se observó diferencias significativas entre los diagnósticos del screening rápido respecto del screening rutinario, con una sensibilidad de un 86 por ciento, especificidad de 100 por ciento y un valor predictivo negativo de un 99 por ciento. Nuestro resultados demuestran la utilidad del screening rápido como método de detección inicial de lesiones positivas, pudiendo ser una alternativa en aquellos laboratorios que presenten considerable, o bien, para reemplazar el método actualmente utilizado

Estudio bacteriológico de la bilis vesicular en un área de alto riesgo de cáncer vesicular / Microbiological study of gallbladder bile in a high risk zone for gallbladder cancer

Background: Gallbladder cancer is frequent in Chile and there is sparse information about the association between this type of cancer and the presence of bacteria in the gallbladder bile. Aim: To determine the presence of aerobic bacteria in gallbladder bile in patients with and without gallbladder cancer. Material and methods: A microbiological analysis of bile and pathological study was performed in 608 gallbladders, obtained during to cholecystectomies performed to 513 women and 95 men aged 44 years old as a mean. Results: Pathological study showed a chronic cholecystitis in 468 cases (77 percent), an acute cholecystitis in 140 (33 percent), cancer in 24 (3.9 percent) and dysplasia in 5 cases (0.8 percent). A positive culture was obtained in 22.5 percent of women and 28.5 percent of males. Twenty seven percent of women over 30 years old had positive cultures compared with 10 percent of younger women (p <0.001). Thirty two percent of acute cholecystitis had positive cultures, compared with 24 percent of chronic cholecystitis (p=0.03). E Coli was isolated in 51 percent of positive cases, streptococci-enterococci in 24 percent, enterobacter sp in 9 percent, klebsiella and proteus in lower proportions. Salmonella sp was isolated in 4 cases, being all women with chronic cholecystitis. Thirteen of 29 cases with cancer or dysplasia had positive cultures (45 percent), compared with 25 percent of patients with inflammatory gallbladder diseases (p=0.02). streptococci-enterococci were isolated in 7 cases and enterobacter sp in three. Conclusions: The presence of salmonella sp in gallbladder bile was not frequent in the studied patients. Its role in the pathogenesis of gallbladder cancer must be reassessed

Sialadenitis crónica esclerosante inespecífica de la glándula submandibular, tumor de Kuttner: caso clínico / Chronic sclerosing unspecific sialadenitis of submandibular gland, Kuttner tumor: report of case

Chronic sclerosing unspecific sialadenitis or KYttner tumor, is an infrequent inflammatory lesion of submandibular gland. We report a 60 years old male presenting with a slowly growing, painless, bilateral submandibular tumor of two years of evolution. Pathological examinations showed marked atrophy of glandular parenchyma with increased fibrous connective tissue and an intense lymphocytic infiltration with lymphoid follicle formation. Lymphocyte population study with kappa, lambda, CD20 and CD45RO antibodies was similar to that observed in reactive lymph nodes. There was no over expression of Bcl-2 gene protein, involved in the phenomenon of apoptosis of glandular tissue, that could explain the pathogenesis of atrophy. This protein was positive only in lymphoid cells and glandular conducts. An immune etiology, with replacement of glandular tissue by lymphoid and fibrous connective tissue is suggested