Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival.

BACKGROUND/AIMS: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%-88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/ HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. METHODS: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. RESULTS: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P<0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. CONCLUSION: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies.

[Mechanical ileus caused by strangulation of the small intestine in a left paraduodenal hernia and in a defect in the root of the mesentery]. / Mehanicki ileus uzrokovan ukljestenjem tankih crijeva u lijevoj paraduodenalnoj kili i u otvoru korijena mezenterija.

A case of mechanical ileus caused by small intestine strangulation into a left paraduodenal hernia and through a circular defect in the root of the mesentery is presented. Whereas left paraduodenal hernia is very rare in the surgical casuistics, its occurrence associated with strangulation through a defect in the mesentery has not been documented up to now to the author's knowledge. The true cause of strangulation ileus was found at operation. Reduction of the intestinal loop from the defect in the root of the mesentery was followed by reduction of the loops from the hernial sac. Both apertures were repaired with great caution using individual sutures without resection of the hernial sac. The early and late postoperative evolutions were uneventful.

[Surgical treatment of injuries and diseases of the spleen]. / Kirusko lijecenje ozljeda i oboljenja slezene.

The paper deals with experiences and procedures in the management of spleen injuries and diseases in 53 patients treated in the Department of Surgery of the Sibenik Medical Centre over the last 15 years. There were 40 patients with spleen injuries, sustained mainly in road traffic accidents (26 or 65%), various accidents in the workplace, at home, knife stabs etc. (14 or 35%). The majority of those injured in road traffic accidents were polytraumatized (77%). Splenectomy was done in 36 patients. Successful splenic salvage was accomplished in 2 cases by the patch procedure. Two children with spleen injuries were treated conservatively, with careful follow-up of laboratory findings, clinical course, scintigraphy and ultrasound findings. Among other diseases splenectomy was done in hypersplenism (3), in spontaneous rupture because of splenomegaly, metastatic carcinoma and hydatid cyst (1 patient respectively). Together with other surgical procedures splenectomy was done in total gastrectomy because of carcinoma (3), in left hemicolectomy also because of carcinoma (2), in haemorrhagic oesophageal varices surgery (1) and in lesion caused by an instrument (1). Because of questionable results, no autologous transplantation was done. There were no cases of postsplenectomy infection.

High c-erbB-2 protein level in colorectal adenocarcinomas correlates with clinical parameters.

Sections of normal colon, adenomas, and adenocarcinomas were examined by immunohistochemistry for the expression of c-erbB-2 proto-oncogene product in order to assess its potential diagnostic value in predicting the malignant potential of these lesions. We compared the degree of epithelial abnormality and clinical parameters, including Dukes' classification and survival time with the extent of immunoperoxidase staining. Sections of normal colon and tubular adenomas examined demonstrated a weak immunostaining localized to the luminal surface cells. However, higher level of c-erbB-2 expression was observed in dysplastic areas of one tubular and one villous adenoma. Out of 40 adenocarcinomas, only 2 samples showed weak immunoreaction, while 38 samples were moderately or strongly positive for c-erbB-2 protein. The intensity of staining correlated positively with the stage of disease and postoperative survival time.

The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer.

BACKGROUND & AIMS: HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor that is amplified and/or overexpressed predominantly in adenocarcinomas. This phenomenon has been most intensively studied in breast carcinoma where its amplification and overexpression correlate with the overall course of disease and poor prognosis. This study was designed to investigate HER-2/neu gene expression in benign and malignant colorectal lesions and to evaluate its prognostic importance in colorectal cancer. METHODS: Two hundred twenty-one samples of normal colon, benign lesions, and colorectal adenocarcinomas were studied for expression of HER-2/neu oncoprotein. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections of primary tumor and lymph nodes was performed. Immunoprecipitation followed by Western blotting of freshly frozen samples of the same tumors were also performed. RESULTS: Normal colon mucosa, benign lesions, and adenocarcinomas clearly differed in the expression levels and histological distribution of p185(HER-2/neu). Normal mucosa was mostly negative, but significant number of benign lesions and adenocarcinomas overexpressed HER-2/neu protein. Adenocarcinomas were significantly more positive than benign lesions. The results show significant correlation with the epithelial abnormality degree and clinical parameters including Dukes' classification and relapse-free and postoperative survival period. CONCLUSIONS: The p185(HER-2/neu) rate expression could serve as an independent prognostic factor in patients with p185(HER-2/neu)-positive colorectal malignancies.