Colesterolosis y cáncer de la vesícula biliar / Association between cholesterolosis and gallbladder cancer

Background: Cholesterolosis is frequently observed in cholecystectomies performed for lithiasis or chronic cholecystitis. Aim: To determine the degree of association between cholesterolosis and gallbladder cancer. Material and Methods: In a prospective study of gallbladder cancer, all gallbladders obtained during cholecystectomies were processed for pathological study, following a special protocol. As part of this study, 23304 surgical samples obtained between 1993 and 2002 were studied, looking for a relationship between cholesterolosis and chronic cholecystitis, adenomas, dysplasia and gallbladder cancer. Results: Seventy nine percent of patients were women. Cholesterolosis was observed in 3,123 cases (13.4 percent). Cholesterolosis was more common in women (14.2 percent) than in men (10.2 percent) (p < 0.001). In the same period, 29 patients were diagnosed with adenomas (0.12 percent), 179 cases with dysplasia not associated with gallbladder cancer (0.8 percent) and 739 gallbladder cancer (3.2 percent). The frequency of cholesterolosis was 13.8 percent in chronic cholecystitis, 13.7 percent in adenomas, 12.1 percent in dysplasias and 1.35 percent in patients with gallbladder cancer (p < 0.01). Of the thirteen cases with gallbladder cancer and cholesterolosis, 10 were early gallbladder carcinomas. Patients with cholesterolosis were 9.2 times less likely to have cancer than those who did not have cholesterolosis. Conclusions: Cholesterolosis has a strong negative association with gallbladder cancer.

Carcinoma subseroso de la vesícula biliar (pT2): valor pronóstico de la expresión de los genes supresores de tumores p53 y p27 en matrices de tejidos / p53 and p27 gene expression in subserosal gallbladder carcinoma

Background: Subserosal carcinoma is the stage that presents the greatest difficulty in the diagnosis therapeutic handling and prognosis evaluation. Aim To study the expression of p53 and p27 genes in subserosal gallbladder cancer. Material and methods: One hundred twenty seven tissue samples of subserosal gallbladder cancer (coming from 112 females aged 62 ± 13years and 15 men aged 67 ± 17years) and 50 control samples were selected to construct tissue arrays. p53 andp27genes were determined by immunohistochemistry. Results: Thirty eight percent of tumors were not detected at the macroscopic examination, 52 percent and 17 percent had lymph node and blood vessel involvement, respectively. Fifty six and 46 percent were positive for p53 and p27, respectively. No association between the expression of both genes and gender, degree of differentiation, lymph node or blood vessel involvement, was observed. Overall five years actuarial survival was 32 percent. Patients with positive or negative p53 expression had a 22 percent and 53 percent survival, respectively (p =0.05). No association between survival and p27 expression was observed. Conclusions: p53 gene expression is a prognostic factor for subserosal gallbladder cancer.

Desde la displasia hasta el cáncer de la vesícula biliar / Natural history of gallbladder cancer Analysis of biopsy specimens

Background: There is scarcity of knowledge about the development of gallbladder cancer. Aim: To study the features of development and progression of gallbladder cancer. Material and methods: Review of histopathological studies of gallbladder obtained in 25,971 cholecytectomies performed in patients aged 45± 16 years, 79 percent females, between 1993 and 2004. Among these, 210 had a dysplasia not associated to cancer and 1,039 had a gallbladder cancer Clinical and morphological parameters of preneoplastic and neoplastic lesions were analyzed. Ninety five percent of patients were followed. Results: All cases of dysplasia were incidental findings. Metaplasia, dysplasia and carcinoma in situ were present in the adjacent mucosa in 66 percent, 81 percent y 69 percent of gallbladder carcinomas, respectively. Twenty five percent of gallbladders studied were carcinomas (mucous carcinoma in 18 percent and muscular carcinoma in 7 percent). Ninety two percent of cases had chronic inflammation in the gallbladder wall. Seventy two percent of mucous carcinomas were not detected macroscopically Five years survival of mucous carcinoma was 92 percent. There was an association between the intensity of the lesion and the age of the patients. The age difference between chronic cholecystitis and gallbladder cancer was 11 years for women and nine for men. Conclusions: From a morphological standpoint, the period in which a dysplasia becomes a carcinoma is approximately 10 years.

Proliferación celular en la mucosa de la vesícula biliar no tumoral en colecistitis crónicas litiásicas. Expresión de Ki-67 en matrices de tejidos / Immunohistochemical expression of Ki-67 as a marker of proliferation in gallbladder mucosa samples with or without cancer

Background: There is paucity of knowledge on the proliferative features of normal or chronically inflamed gallbladder and the mechanisms of development of gallbladder cancer. Aim: To study the proliferation features of non tumoral gallbladder mucosa through the expression of Ki-67 antigen in tissue micro array analysis. Material and methods: The immunohystochemical expression of Ki-67 in tissue micro array was studied in 96 samples of non tumoral gallbladder mucosa (coming from 74 females aged 45±16 years and 22 males aged 53±16 years) and 102 samples of gallbladder cancer (coming from 84 females aged 62± 14 years and 18 males aged 70± 13 years). Results: The staining index of Ki-67 expression was 19±25 percent (range 096-8996) in samples of non tumoral mucosa and 46±29 percent (range 396-9896) in gallbladder cancer (p <0.01). Ki-67 was expressed in less than 10 percent of epithelial cells in 55 percent of non tumoral mucosa samples and 6 percent of gallbladder cancer samples. Seventy five percent of gallbladder cancer samples had a staining index of more than 20 percent. An expression of Ki-67 over 20 percent or 50 percent was observed in 25 percent and 15 percent of non tumoral mucosa samples, respectively Conclusions: Non tumoral gallbladder mucosa samples have a high proliferation index, measured using Ki-67 immunohystochemical expression. There is a group of samples with cellular hyper-proliferation that maybe related to the pathogenesis of gallbladder cancer.

Inestabilidad microsatelital en lesiones preneoplásicas y neoplásicas del cuello uterino: Correlación con el genotipo del virus papiloma humano / Microsatellite instability and human papilloma virus genotypes in preneoplastic and neoplastic uterine cervix lesions

Background: The association between some specific human papilloma virus (HPV) types and cervix cancer is well known. However, the genetic conditions that favor the development of cervical cancer are less well known. Aim: To determine the presence of satellite instability (MSI) in preneoplastic and neoplastic lesions of the cervix and correlate these findings with HPV genotypes. Material and methods: Biopsy samples of cervical lesions were studied. Sixteen had low grade lesions, 22 had high grade lesions and 28 had an epidermoid cancer. Viral types were identified with polymerase chain reaction, dot-blot hybridization and restriction fragment length polymorphism. MSI was determined using a panel of eight highly informative microsatellites. Results: Microsatellite instability in at least one locus was observed in 91, 56 and 69 percent of low grade lesions, high grade lesions and epidermoid carcinomas, respectively. MSI-High grade, MSI-Low grade instability and microsatellite stability were observed in 5, 60 and 46 percent of samples, respectively. Two of three samples with high grade instability had HPV 52 genotype. Other viral subtypes had frequencies that ranged from 78 percent to 100 percent, with the exception of HPV16 that was present in only 53 percent of samples with low grade instability. Conclusions: Two thirds of biopsy samples from cervical lesions had MSI, mechanism that can be involved in the first stages of cervical carcinogenesis. The low frequency of high grade instability, its association with HPV52 and the low frequency of HPV16 in samples with low grade instability, suggest different coadjutant mechanisms in cervical carcinogenesis

Inactivación del gen CDKN2A (p16) en cáncer de la vesícula biliar / 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 trans-criptionally 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.

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

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

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

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

Expresión de la proteína del gen Bcl-2 en tumores de glándulas salivales / Gene Bcl-2 protein expression in salivary gland tumors

Background: Salivary gland tumors have heterogeneous pathological features. Oncogene Bcl-2 product expression inhibits apoptosis and therefore is important for tumor proliferation. Aim: To assess the immunohistochemical gene Bcl-2 protein expression in salivary gland tumors. Material and methods: Twenty seven salivary gland tumors were selected from the archives of the Pathology Department of Temuco Regional Hospital. There were 20 pleiomorphic adenomas, 4 cystic adenoid carcinomas and three mucoepidermoid carcinomas. Immunohistochemical gene Bcl-2 protein expression was determined in paraffin included pathological slices. Results: All pleiomorphic adenomas expressed the protein, specially in tubulo ductal structures, solid and trabecular areas. All cystic adenoid carcinomas expressed the protein in myoepithelial cells. Two mucoepidermoid carcinomas were positive, only in the epidermoid areas. Conclusions: immunohistochemical gene Bcl-2 protein was expressed in virtually all benign and malignant salivary gland tumors. This observation suggest an important role of this protein in the development of these tumors

Cáncer colorrectal: utilización de la técnica azul victoria en la detección de las permeaciones tumorales vasculares venosas: importancia pronóstica / Colorectal cancer: use of the victory blue technique in the detection of the venous vascular tumoral permeations: prognostic importance

La detección del compromiso vascular ha demostrado ser un factor pronóstico importante en algunas neoplasias del tubo digestivo, sin embargo, no ha recibido suficiente atención en su procesamiento de rutina. El objetivo de este trabajo es cuantificar la detección de permeaciones vasculares venosas con la técnica de Azul Victoria (de alta afinidad por las fibras elásticas) y evaluarlas como factor pronóstico en pacientes con cáncer de colon y recto. Se estudiaron 53 pacientes operados por carcinomas de colon y recto con la técnica de Azul Victoria. La distribución de la muestra no mostró diferencia por sexo, con una edad promedio de 63 años. El 96 por ciento correspondió a tumores avanzados, la totalidad de éstos correspondieron a adenocarcinomas, siendo el tipo tubular el más frecuente con 74 por ciento. En el 58 por ciento de los casos no se encontró metástasis ganglionar linfática. Se encontraron permeaciones vasculares de tipo venoso en el 43,4 por ciento de los casos con la técnica de Azul Victoria, a diferencia del 20,5 por ciento encontrado con Hematoxilina eosina (p<0,001). Al analizar el seguimiento de los pacientres se encontró menor sobrevida en el grupo de pacientes con permeaciones con respecto al grupo que no las tenía (Kaplan Meier p=0,04)

Expresión de la proteína del gen supresor de tumores p53 en el carcinoma de próstata / Expression of the supressor gene protein of p53 tumors in prostatic carcinoma

El cáncer de la próstata es una de las neoplasias más frecuentes en hombres mayores de 50 años. La mutación y expresión del gen supresor de tumores p53 ha sido demostrado en la carcinogénesis de múltiples neoplasias y en alrededor del 40 por ciento de los cánceres de la próstata. El objeto de este trabajo es determinar la frecuencia de la expresión del gen p53 en el carcinoma prostático. Se estudia la expresión de la proteína p53 en 35 carcinomas prostáticos mediante la técnica de inmunohistoquímica con anticuerpo monoclonal. Los pacientes se distribuyeron por etapas clínicas: Etapa A = 4 casos; Etapa B = 5 casos; Gleason entre 4 y 7 y el 16 por ciento entre 8 y 10. El promedio de edad fue 70,7 años (límites 53-85 años). No se observó tinción positiva en ninguno de los controles ni en los tumores en etapas A y B. Se observó tinción positiva de la proteína del gen p53 en 11 de los 35 casos (31,4 por ciento), 17 por ciento en los en Etapa C y un 64,2 por ciento tumores en los en Etapa D (p = 0,01). No se observó diferencia respecto del índice de Gleason aun cuando los tumores mejor diferenciados presentaron menor positividad. Nuestros resultados muestran que la proteína del gen supresor de tumores p53 no guarda relación con el índice de Gleason y sólo se observa en tumores avanzados, especialmente en la Etapa D, y su determinación puede contribuir significativamente a una mejor evaluación preoperatoria de los pacientes