ABSTRACT
We used immunohistochemical analysis to study the expression and prognostic impact of cyclin B1, a key molecule for G2-M phase transition during the cell cycle, in a series of 342 curatively resected colorectal carcinomas. In 269 tumors (78.7%), high expression of cyclin B1 in more than 10% of tumor cells was observed, but there was no association between cyclin B1 expression and histopathologic tumor features. Univariate analysis revealed no impact on disease-free and overall survival. Multivariate analysis revealed pT and pN categories, extramural blood vessel invasion, and low-grade tumor cell differentiation as independent prognostic predictors for overall survival, and pT and pN categories and tumor site for disease-free survival. According to our results, high expression of cyclin B1 is a frequent and early event in colorectal carcinomas. However, cyclin B1 expression is neither a predictor of prognosis in patients with colorectal cancer nor a suitable tool for identifying subgroups of patients at higher risk for disease recurrence.
Subject(s)
Colorectal Neoplasms/chemistry , Cyclin B/analysis , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Cyclin B1 , Disease-Free Survival , Female , G2 Phase , Humans , Immunohistochemistry , Intestinal Mucosa/chemistry , Male , Middle Aged , Mitosis , PrognosisABSTRACT
During mitosis, the spindle checkpoint delays the onset of anaphase until all chromosomes have attached properly to the mitotic spindle, preventing chromosome missegregation. BUB (budding uninhibited by benzimidazole) 1 is one of the key components of this checkpoint. BUB1 mutations are rare in cancer tissues and no mutations have been identified in gastric cancer. In mice, immunodepletion of BUB1 abolished the spindle checkpoint. Thus, aberrant expression of BUB1 protein could impair mitotic checkpoint function, resulting in aneuploidy, a common phenomenon in gastric cancer. In the present study, an antibody was generated against BUB1 and its expression was studied in gastric cancer tissue sections (n = 80) by immunohistochemistry. Nuclear BUB1 expression was found in all gastric cancer cases. The proportion of tumour cells expressing BUB1 was significantly greater in diffuse-type than in intestinal-type gastric carcinoma (p < 0.001). No correlation was found between BUB1 expression and deoxyribonucleic acid (DNA) ploidy, microsatellite instability or any other histopathological parameters investigated. To the authors' knowledge, this is the first study of BUB1 protein expression in gastric cancer tissues. Different BUB1 protein expression levels in intestinal- and diffuse-type gastric cancer may provide further evidence of a potential link between different genetic pathways and morphological phenotype in gastric carcinogenesis. However, further studies are needed to establish whether there is an association between BUB1 protein expression level and mitotic spindle checkpoint function in gastric cancer.
Subject(s)
Adenocarcinoma/metabolism , DNA, Neoplasm/analysis , Neoplasm Proteins/metabolism , Protein Kinases/metabolism , Stomach Neoplasms/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Gastric Mucosa/metabolism , Humans , Immunoenzyme Techniques , Male , Microsatellite Repeats , Middle Aged , Neoplasm Proteins/immunology , Ploidies , Protein Kinases/immunology , Protein Serine-Threonine Kinases , Sensitivity and Specificity , Stomach Neoplasms/genetics , Stomach Neoplasms/pathologyABSTRACT
Transforming growth factor beta type II receptor (TGFbeta-IIR) has been found to be altered in primary gastrointestinal carcinomas. So far relatively few facts are known about the expression of TGFbeta-IIR in primary gastric cancer. Therefore, in the present study, TGFbeta-IIR expression was analyzed in 130 primary gastric carcinomas and correlated with clinicopathological findings, the presence of a mutator phenotype, the mutational status of the TGFbeta-IIR polyadenine tract and survival. TGFbeta-IIR expression was analyzed immunohistochemically. Microsatellite instability was evaluated using a PCR-based assay and the polyadenine run inside the TGFbeta-IIR gene was sequenced. A complete loss of TGFbeta-IIR expression could be found in 55 (42.3%) of these carcinomas. Loss of TGFbeta-IIR expression was significantly correlated with diffuse-type carcinomas according to the Lauren classification as well as with signet ring cell carcinomas and a lower grade of differentiation. No correlation was found with the overall prognosis, the presence of a mutator phenotype, or a mutated TGFbeta-IIR. Thus, our data suggest the existence of a further definite subgroup of diffuse-type gastric carcinomas with altered TGFbeta-IIR expression, independent from a mutator phenotype with TGFbeta-IIR gene mutations. However, according to our results, in gastric cancer neither loss of TGFbeta-IIR expression nor mutations of the TGFbeta-IIR are of prognostic value.
