Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma.

CONTEXT: Carcinoembryonic antigen (CEA) can be detected in colorectal tumor tissue but its role in the survival of patients remains controversial. OBJECTIVE: To characterize the expression of tissue CEA using immunohistochemical staining in colorectal tumors and to analyze the relationship between this finding and preoperative plasmatic level of CEA, morphologic features and survival of patients operated with curative intent for colorectal carcinoma. METHOD: Forty-seven patients were included in the study: 18 (38.3%) males and 29 (61.7%) females, with a mean age of 67.8 +/- 9.7 years (37 to 84 years). Immediately before laparotomy, pre-operative serum levels of CEA were obtained where normal levels were considered < or =2.5 ng/mL for non-smokers, and < or =5.0 ng/mL for smokers. CEA immunohistochemical studies were carried out using anti-human CEA monoclonal mouse antibody. The expression of immunostaining for each neoplasia was classified according to the pattern of CEA tissular distribution into apical or cytoplasmic. The variables considered for the statistical analysis were plasmatic preoperative CEA level, location of the lesion within the large intestine, lesion diameter, lymph node involvement, Duke's classification, vein invasion, grade of cellular differentiation, survival and pattern of CEA tissular distribution. The statistical models utilized were Spearman's correlation and the Mann-Whitney, Kruskal-Wallis and Student t tests. Patients' survival was analyzed using the Kaplan-Meier method. RESULTS: The mean preoperative CEA value was 15.4 +/- 5.5 ng/mL (0.2 to 92.1 ng/mL). The neoplasm was located in the colon in 29 (61.7%) and in the rectum in 18 (38.3%) patients. Eight (17.0%) patients were classified as Duke's stage A, 22 (46.8%) as stage B and 17 (36.2%) as stage C. On immunohistochemical studies, the pattern of CEA tissular distribution was apical in 33 (70.2%) patients and cytoplasmic in 14 (29.8%) patients. Patients with apical patterns presented a mean sera CEA level of 15.5 +/- 6.5 ng/mL while those with cytoplasmic pattern attained a mean sera CEA level of 15.1 +/- 7.3 ng/mL, with no significant difference between these values (P = 0.35). Apical distribution of CEA occurred in 6 (12.8%) Duke A, 18 (38.2%) Duke B and 9 (12.2%) Duke C patients, while cytoplasmic CEA tissular distribution was observed in 2 (4.2%) Duke A, 3 (6.4%) Duke B and 9 (19.1%) Duke C patients. Patients with Duke B neoplasms presented significantly more apical CEA tissular distribution patterns (P = 0.049) than subjects with cytoplasmic CEA tissular patterns. The apical CEA tissular distribution pattern in neoplasms was significantly more frequent in neoplasms with no lymph node compromise compared to the cytoplasmic pattern (P = 0.50). However, no significant differences were seen between apical and cytoplasmic CEA tissular distribution patterns in terms of colon or rectal site (P = 0.21), lesion diameter across greatest axis (P = 0.19), vein invasion (P = 0.13) or degree of cellular differentiation (P = 0.19). Of the 47 patients operated, 33 (70.2%) survived for more than 5 years where mean survival was 31.1 +/- 5.6 months. Survival between patients with apical and cytoplasmic CEA tissular distribution showed no significant difference (P = 0.38). CONCLUSIONS: Although the apical distribution pattern of CEA was significantly more frequent in more advanced stages of Duke's classification, the CEA tissular distribution presented no relationship with serum CEA levels, morphological features of the neoplasm or survival of patients undergoing curative colorectal carcinoma resection.

Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma / Valor prognóstico da distribuição do antígeno carcinoembriônico (CEA) no tecido neoplásico do carcinoma colorretal

CONTEXT: Carcinoembryonic antigen (CEA) can be detected in colorectal tumor tissue but its role in the survival of patients remains controversial. OBJECTIVE: To characterize the expression of tissue CEA using immunohistochemical staining in colorectal tumors and to analyze the relationship between this finding and preoperative plasmatic level of CEA, morphologic features and survival of patients operated with curative intent for colorectal carcinoma. METHOD: Forty-seven patients were included in the study: 18 (38.3 percent) males and 29 (61.7 percent) females, with a mean age of 67.8 ± 9.7 years (37 to 84 years). Immediately before laparotomy, pre-operative serum levels of CEA were obtained where normal levels were considered <2.5 ng/mL for non-smokers, and <5.0 ng/mL for smokers. CEA immunohistochemical studies were carried out using anti-human CEA monoclonal mouse antibody. The expression of immunostaining for each neoplasia was classified according to the pattern of CEA tissular distribution into apical or cytoplasmic. The variables considered for the statistical analysis were plasmatic preoperative CEA level, location of the lesion within the large intestine, lesion diameter, lymph node involvement, Duke's classification, vein invasion, grade of cellular differentiation, survival and pattern of CEA tissular distribution. The statistical models utilized were Spearman's correlation and the Mann-Whitney, Kruskal-Wallis and Student t tests. Patients' survival was analyzed using the Kaplan-Meier method. RESULTS: The mean preoperative CEA value was 15.4 ± 5.5 ng/mL (0.2 to 92.1 ng/mL). The neoplasm was located in the colon in 29 (61.7 percent) and in the rectum in 18 (38.3 percent) patients. Eight (17.0 percent) patients were classified as Duke's stage A, 22 (46.8 percent) as stage B and 17 (36.2 percent) as stage C. On immunohistochemical studies, the pattern of CEA tissular distribution was apical in 33 (70.2 percent) patients and cytoplasmic...

CONTEXTO: O antígeno carcinoembrionário (CEA) pode ser detectado no tecido do carcinoma colorretal, mas seu papel na sobrevivência dos doentes permanece controverso. OBJETIVO: Caracterizar a expressão do CEA tecidual com coloração imunoistoquímica na neoplasia colorretal e analisar a relação entre esse achado e os níveis plasmáticos pré-operatórios do CEA, aspectos morfológicos e a sobrevivência dos doentes operados com intenção curativa de carcinoma colorretal. MÉTODO: Quarenta e sete doentes foram incluídos neste estudo: 18 (38,3 por cento) homens e 29 (61,7 por cento) mulheres, com média de idade de 67,8 ± 9,7 anos (37 to 84 anos). Imediatamente antes da laparotomia, foram obtidos os níveis plasmáticos pré-operatórios do CEA. Níveis séricos pré-operatórios normais de CEA foram considerados < 2,5 ng/mL para não-fumantes e <5,0 ng/mL para fumantes. O estudo imunoistoquímico do CEA foi realizado utilizando anticorpo monoclonal de rato anti-CEA humano. A expressão da imunocoloração de cada neoplasia foi classificada de acordo com o padrão de distribuição tecidual do CEA em apical ou citoplasmática. As variáveis consideradas para a análise estatística foram os níveis plasmáticos pré-operatórios do CEA, localização da lesão no intestino grosso, diâmetro da lesão, comprometimento dos linfonodos, classificação de Dukes, invasão venosa, grau de diferenciação celular, sobrevivência e padrão da distribuição tecidual do CEA. Os modelos estatísticos utilizados foram correlação de Spearman, teste de Mann-Whitney, teste de Kruskal-Wallis e teste t de Student. A sobrevivência dos doentes foi analisada utilizando-se o método de Kaplan-Meier. RESULTADOS: O valor médio de CEA pré-operatório foi de 15,4 ± 5,5 ng/mL (0,2 a 92,1 ng/mL). A neoplasia estava localizada no colo em 29 (61,7 por cento) e no reto em 18 (38,3 por cento) doentes. Oito (17,0 por cento) doentes foram classificados como estádio A de Dukes, 22 (46,8 por cento) como estádio B e 17...

Bcl-2 expression in rectal cancer

BACKGROUD: Proteins involved in apoptosis process seem to play an important role in colorectal carcinogenesis AIM: To determine the prevalence of bcl-2 protein immunohistochemical expression and its relation with clinical and histopathological variables of rectal adenocarcinoma. PATIENTS AND METHODS: One hundred and thirty-two patients operated at "Hospital de Clínicas de Porto Alegre", Porto Alegre, RS, Brazil, between 1988 and 1999 were studied through immunohistochemical reaction using a monoclonal antibody anti-bcl-2 on formalin-fixed, paraffin-embedded tissue samples RESULTS: The prevalence of bcl-2 protein was 29.5 percent. There was a significant increased number of positive bcl-2 cases among women as compared to men. There was no significant association between bcl-2 and age, tumour site, histological grade, mucin production, depth of invasion, lymphatic involvement, distant metastasis or stage, despite a trend showing decreased immunoreactivity to bcl-2 among poorly and moderately differentiated tumours, as well as disseminated disease CONCLUSIONS: Analysis of bcl-2 protein expression in tumour tissues, as well as other oncoproteins, may have a role in predict therapeutic response and prognosis of colorectal cancer. However, the potential use of bcl-2 protein assessment in the clinical set for management of rectal cancer remains to be determined.

RACIONAL: As proteínas envolvidas no processo de apoptose parecem desempenhar papel importante na carcinogênese colorretal. OBJETIVOS: Determinar a prevalência da expressão imunoistoquímica da proteína bcl-2 e sua relação com variáveis clínicas e histopatológicas do câncer de reto. PACIENTES E MÉTODOS: Cento e trinta e dois pacientes operados no Hospital de Clínicas de Porto Alegre, RS, entre 1988 e 1999 foram estudados através de reação imunoistoquímica, utilizando um anticorpo monoclonal anti-bcl-2 em amostras teciduais fixadas em formalina e parafinizadas. RESULTADOS: A prevalência da proteína bcl-2 foi de 29,5 por cento. Houve aumento significativo no número de casos bcl-2 positivo entre mulheres quando comparado aos homens. Não houve associação significativa entre bcl-2 e idade, sítio do tumor, grau histológico, produção de muco, profundidade de invasão, envolvimento linfático, metástases distantes ou estágio, apesar de uma tendência demonstrando imunorreatividade ao bcl-2 diminuída entre os tumores pouco e moderadamente diferenciados, bem como para doença disseminada. CONCLUSÕES: A análise da expressão da proteína bcl-2 em tecidos tumorais, bem como outras oncoproteínas, pode ter um papel em predizer a resposta terapêutica e o prognóstico do câncer colorretal. Entretanto, o uso potencial da avaliação da proteína bcl-2 na prática clínica no manejo do câncer de reto permanece a ser determinado.

Flat elevated lesions of the colon and rectum: a spectrum of neoplastic and nonneoplastic entities.

The aim of this prospective study is to establish the frequency and the type (neoplastic and nonneoplastic) lesions defined endoscopically as flat elevated lesion (FEL) in the colon and rectum, as well as to compare flat adenomas (FAs) to polypoid lesions of the same size with morphometric and immunohistochemical analysis. One hundred nineteen patients were studied through fibrocolonoscopy with chromoscopy (indigo carmine spray). All detected lesions (total of 195) were removed, and FELs measuring 10 mm or smaller were also selected. Using histopathologic criteria, they were divided in neoplastic (adenomas and carcinomas) and nonneoplastic ones. In neoplastic lesions, the following parameters were evaluated to compare FAs with polypoid lesions: morphometric studies with Index of Structural Atypia (ISA) and Stratification Index (SI), evaluation of cellular proliferation with label index of Ki-67, and expression of p53 protein. Of 195 lesions resected, only 33 (17%) met the endoscopic requirements for FELs. Twelve (36.4%) were neoplastic and 21 (63.6%) considered nonneoplastic. Among the FAs, there were a percentage of high-grade (severe dysplasia) significantly more frequent than observed in polypoid lesions (16.7% vs 2.6%). In addition, the SI, Ki-67 label index and p53 positivity were significantly higher in FAs. The ISA also reached significant differences between both groups of adenomas. Non-neoplastic FELs included different entities such as hyperplasic polyps, focuses of colitis, normal mucosa, and scars. The endoscopic elements analyzed were shared between nonneoplastic FELs and FAs. A central depression, when air was properly insufflated, considered typical in neoplastic lesions, was frequently observed in nonneoplastic lesions. Following the endoscopic criteria of FELs, nonneoplastic lesions predominated over the adenomatous lesions, demonstrating that FELs and FAs are not homologous terms. The frequency of high-grade dysplasia was significantly more elevated in the adenomatous FELs than in polypoid adenomas. The ISA, SI, p53 expression, and Ki-67 label index were helpful in differentiating adenomatous FELs from polypoid lesions. Flat elevated lesions selected by endoscopic criteria are, in fact, a heterogeneous population of lesions.

Bcl-2 expression in rectal cancer.

BACKGROUND: [corrected] Proteins involved in apoptosis process seem to play an important role in colorectal carcinogenesis AIM: To determine the prevalence of bcl-2 protein immunohistochemical expression and its relation with clinical and histopathological variables of rectal adenocarcinoma. PATIENTS AND METHODS: One hundred and thirty-two patients operated at "Hospital de Clínicas de Porto Alegre", Porto Alegre, RS, Brazil, between 1988 and 1999 were studied through immunohistochemical reaction using a monoclonal antibody anti-bcl-2 on formalin-fixed, paraffin-embedded tissue samples RESULTS: The prevalence of bcl-2 protein was 29.5%. There was a significant increased number of positive bcl-2 cases among women as compared to men. There was no significant association between bcl-2 and age, tumour site, histological grade, mucin production, depth of invasion, lymphatic involvement, distant metastasis or stage, despite a trend showing decreased immunoreactivity to bcl-2 among poorly and moderately differentiated tumours, as well as disseminated disease CONCLUSIONS: Analysis of bcl-2 protein expression in tumour tissues, as well as other oncoproteins, may have a role in predict therapeutic response and prognosis of colorectal cancer. However, the potential use of bcl-2 protein assessment in the clinical set for management of rectal cancer remains to be determined.