Evaluation of P53, E-cadherin, Cox-2, and EGFR protein imunnoexpression on prognostic of resected gallbladder carcinoma / Avaliação da imuno-expressão das proteínas P53, E-caderina, Cox-2 e EGFR no prognóstico do carcinoma de vesícula biliar ressecado

BACKGROUND: Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. AIM: To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. METHODS: Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. RESULTS: Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. CONCLUSION: Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue. .

RACIONAL: O carcinoma de vesícula biliar apresenta mau prognóstico. O tratamento de escolha é a ressecção cirúrgica que está associado à alta morbimortalidade. O melhor conhecimento de fatores prognósticos pode resultar em melhor seleção dos doentes para o tratamento cirúrgico e multimodal. OBJETIVOS: Avaliar a imunoexpressão tecidual das proteínas P53, E-caderina, Cox-2 e EGFR e correlacionar com a sobrevida do adenocarcinoma de vesícula biliar ressecado. MÉTODO: Os dados clínicos, laboratoriais, cirúrgicos e anatomopatológicos de uma série de doentes operados por adenocarcinoma de vesicula biliar foram coletados. A casuística total foi de 42 doentes. A mediana de idade foi de 72 anos (35-87). Foram sete homens e 35 mulheres. A distribuição da lesão de acordo com TNM foi a seguinte: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Vinte três doentes realizaram ressecção radical (R0) enquanto 19 operação paliativa (R1-R2). Um bloco de tissue microarray foi confeccionado com tecido neoplásico de cada doente. para avaliação da imunoexpressão das proteínas P53, E-Caderina, COX-2 e EGFR. Esses achados foram correlacionados com prognóstico final dos doentes. RESULTADOS: A sobrevida estimada em cinco anos foi de 28%. A mediana de sobrevida global foi de oito meses. Apenas a imunoexpressão da proteína EGFR foi considerada variável independente no prognóstico dos doentes. CONCLUSÃO: Pior prognóstico teve relação com a imunoexpressão aumentada da proteína EGFR no tecido tumoral. .

Carcinoma subseroso de la vesícula biliar: expresión del complejo caderina-catenina / Subserous gallbladder carcinoma: expression of cadherine-catenine complex

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

Los antígenos del sistema HLA clases I y II en la sangre periférica de pacientes con cáncer vesicular y colelitiasis y de pacientes con colelitiasis sin cáncer / The antigens of the HLA system I and II types in peripheric blood in patients with gallbladder cancer and cholelithiasis and in patients with cholelithiasis without cancer

El cáncer de la vesícula biliar (CV) es una enfermedad de lata prevalencia en Chile y habitualmente asociada a colelitiasis. En 110 pacientes con CV y colelitiasis, y en 106 con colelitiasis sin antecedentes neoplásicos se investigan los antígenos del sistema HLA (A, B, C, DR y DQ), buscando marcadores que permitan asociar colelitiasis con CV y analizando el comportamiento del sistema en relación a la sobrevida de pacientes con CV. Se encontraron asociaciones facilitadoras de CV en los antígenos DR6 (tipificado sin splits) (p< 0,006 - RR 1,64); en la suma de todos los splits DR6 incluido el antígeno DR6 (p< 0,006 -RR 1,47) y DQ3 (p< 0,006 - RR 1,45). Se hallaron asociaciones protectoras de CV en los antígenos A19 (p< 0,006); DR11(5) (p< 0,0001 - RR 0,68) y DQ7(3) (p< 0,008 - RR 0,63). La sobrevida mayor a 5 años de los pacientes con CV se asoció a los antígenos DR5 (p< 0,0001) y DR52 (p< 0,02). Los hallazgos sugieren una asociación entre CV y algunos antígenos HLA, sin embargo, es prematuro recomendar su uso en la práctica clínica habitual. Es necesario estudiar a nivel de genética molecular los alelos responsables de dichas asociaciones, en partícular el alelo DR52b

CA 19-9 y antígeno carcino-embrionario en cáncer de la vesícula biliar / CA 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 percent) patients with cancer, in two patients free of disease and 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 percent) and in 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 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 hear in mind that studied patients had advanced tumors

Cáncer de la vesícula biliar: expresión inmunohistoquímica de la proteína relacionada con receptor estrogénico (p29) y de la proteína inducida por estrógeno (pS2) / Cáncer of gallbladder: immunohistochemical expression of estrogen receptor related protein (p29) and estrogen induced protein (pS2)

The high frequency of gallblader cancer in women suggest a role for estrogens in its development. The aim of this study was to study the immunohistochemical expression in 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 percent) and pS2 in 15 cases (60 percent). p29 was positive in 40 percent and pS2 in 32 percent of tumors. p29 expressed with higher frequency in metastases than in primary tumors (57 and 31 percent respectively, p<0.02). Early tumors had a significantly lower expression of p29 than advanced tumors or than metastases. Both proteins expressed in 18 percent of samples (synchronic expression) whereas one of both proteins did so in 60 percent of cases (asynchronic expression). We conclude that most gallbladder cancer samples express proteins associated to estrogen receptor or induced by estrogens

Carcinoma de la vesícula biliar: expresión de productos de los oncogenes C-MYC y RAS-P-21 / Carcinoma of gallblader: expression of products of C-MYC and RAS-P-21 oncogene

The expression of c-myc and p-ras-21 oncogenes was studied using an immunohistochemical method with monoclonal antibodies in 126 samples of gallbladder carcinoma (103 primary tumors and 23 metastatic lesions). Twenty five gallbladder samples without tumor evidence were used as controls. C-myc oncoprotein was positive in one control sample and p-ras-21 oncoprotein was negative in all. Among primary carcinomas c-myc was positive in 9 (9 per cent) and 4 (4 per cent); among metastatic carcinomas c-myc was positive in 6 (26 per cent, p=0.03 vs primary carcinoma) and p-ras-21 in 11 (48 per cent, p <0.001 vs primary carcinoma). There was a non significant association between c-myc and p-ras-21 expression and degree of histological differentiation and levelñ of tumoral infiltration. It is concliuded that c-myc and p-ras-21 oncoprotein expression is observed in less than 10 per cent of primary gallbladder carcinomas and that this expression is significantly higher in metastatic cells

Expresión inmunohistoquímica del antígeno carcinoembrionario en el cáncer de la vesícula biliar / Immunohistochemical expression of the carcinoembryonic antigen in gallbladder cancer

Immunohistochemical techniques using monoclonal antibodies were used to investigate the carcinoembryonic antigen (CEA) in gallbladders from 26 patients with gallbladdeer cancer and 26 patients without cacer, including normal mucosa, areas of pyloric metaplasia and areas identified by the presence of "clear cells". All carcinomas were strongly positive for CEA but 61% of noncancerous samples were also positive. However, only 1 of the last samples was strongly positive. According to hystologic type the positivity for CEA in noncancerous samples was 6/11 in normal mucosa, 6/8 in samples with intestinal metaplasia and 1/8 in samples with pyloric metaplasia (p < 0.05). Thus a negative reaction for CEA is 100% specific for absence of cancer. If mild reactions are disregarded, strong reaction for CEA is 81% specific for cancer

Evaluación inmunológica e inmunogenética de pacientes con cáncer de la vesícula biliar: comunicación preliminar / Immunologic and immunogenetic evaluation of the patients with gallbladder cancer: preliminary comunication

Se estudiaron cinco pacientes con cáncer de la vesícula biliar (CV) con prolongada sobrevida postoperatoria (4-12 años): Grupo A. Se compara este grupo con cinco pacientes intervenidos recientemente, cuya enfermedad está avanzada: Grupo B y con cinco enfermos sometidos a colecistectomía por litiasis y sin cáncer: Grupo C (control). En el Grupo A hubo 2 casos con antecedentes de cáncer en otras localizaciones (mama, útero y recto), lo que hace suponer una predisposición neoplásica y una especial inmunidad contra el cáncer. En este estudio preliminar, la respuesta inmunitaria de los pacientes del Grupo A y C fue similar. En los enfermos del Grupo B, se observó reducción de la inmunocompetencia con la progresión de la enfermedad, especialmente en los test cutáneos. En el estudio histoquímico, en los Grupos A y B, las poblaciones celulares relacionadas con la inmunidad se situaron en la periferia del tumor pero sólo en las del Grupo A se encontraron en el interior de la masa tumoral. En la investigación inmunogénetica se observó que el antígeno HLA-DR4 se encuentra en una proporción mayor en los pacientes con CV (38%), en comparación con la población chilena nornal (29%). Se incluye que es necesario: a. Proseguir la investigación, aumentando el número de casos; b. trabajar en el estudio inmuno histoquímico sólo con vesículas frescas, y c. Seguir investigando los antígenos del sistema HLA, tanto en pacientes portadores de cáncer vesícular, como en aquéllos con simple colelitiasis