cyclin-d1 and Common-Bile-Duct-Neoplasms

Previous studies on the molecular alterations in ampullary adenocarcinoma (AA) are limited, and little is known about their clinical implications. The objective of this study is to examine the expression of p53, p21, cyclin D1, and Bcl2 and their clinical significance in patients with AA. Tissue microarrays were constructed using archival tissue from 92 patients with AA who underwent pancreaticoduodenectomy at our institution. Each tumor was sampled in triplicate with a 1.0-mm punch from representative areas. The expression of p53, p21, cyclin D1, and Bcl2 was evaluated by immunohistochemistry, and the staining results were correlated with clinicopathological features and survival. Among 92 cases studied, overexpression of p53, p21, cyclin D1, and Bcl2 was observed in 58.7%, 39.2%, 71.7%, and 5.4% of tumors, respectively. Patients whose tumor showed high level of cyclin D1 expression had higher risk of disease recurrence (P = .02) and worse recurrence-free and overall survivals after pancreaticoduodenectomy than did those with no or low cyclin D1 expression (P = .027 and P = .02, respectively). In multivariate analysis, cyclin D1 expression was an independent prognostic factor for both recurrence-free and overall survival (P < .05). However, there was no significant correlation between p53, p21, or Bcl2 expression and survival (P > .05). Our study showed that p53, p21, and cyclin D1, but not Bcl2, are frequently overexpressed in AAs. Cyclin D1 overexpression is associated with increased risk of disease recurrence and worse survival in patients with AA after resection.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Common Bile Duct Neoplasms; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Female; Humans; Male; Middle Aged; Pancreaticoduodenectomy; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53

The majority of the tumors in periampullary region are pancreatic and ampulla of Vater carcinomas. The aim of this study was to compare histopathological features of ampulla of Vater carcinomas with pancreatic ductal adenocarcinomas and to determine diagnostic and predictive values of p16 protein and cyclin D1 expression.. Tissue samples from pancreatic ductal adenocarcinomas and ampulla of Vater carcinomas were obtained from 31 patients who underwent pancreticoduodenectomy for periampullary carcinoma. The study group was composed of 12 women and 19 men. Their median age was found to be 62.32 years (range 26-85 years). The parameters analyzed in the study included lymph node metastases, perineural invasion, differentiation, duodenal invasion, grade of intraepithelial neoplasia and p16 and cyclin D1 expression in tumoral and peritumoral pancreatic tissues.. In both tumor groups, the loss of p16 protein expression was significantly correlated with perineural invasion (p = 0.0001). Perineural invasion was more frequent in the pancreatic ductal adenocarcinoma group than the ampulla of Vater carcinoma group (p = 0.01). When desmoplasia and lymphoplasmacytic stromal infiltration were examined, desmoplastic reaction was significantly higher in pancreatic ductal adenocarcinomas than ampulla of Vater carcinomas (p = 0.01). No significant difference was observed between tumor groups for Cyclin D1 (p > 0.05).. The results suggest that loss of p16 protein expression may be a sign for poor prognosis in periampullary cancers that is correlated mainly with perineural invasion. Desmoplastic stromal reaction may be a distinctive feature for pancreatic ductal adenocarcinoma compared with ampulla of Vater carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Common Bile Duct Neoplasms; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Lymph Nodes; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Pancreaticoduodenectomy; Prognosis

Carcinomas of the ampulla of Vater are rare and assumed to generally arise from preexisting adenomas (adenoma-carcinoma sequence). Histologically, distinct subtypes can be distinguished that were shown to differ significantly in terms of clinical outcome. Since pathologists usually receive bioptic tissue samples of ampullary tumors obtained during endoscopy, accurate classification of carcinoma subtypes can sometimes be difficult on morphological criteria alone. We therefore performed immunohistochemistry using a panel of established marker proteins (CK7, CK20, p21, p27, ESA, bax, and ephrin-B2) on 175 carcinoma, 111 adenoma, and 152 normal mucosa specimens of the ampulla of Vater and identified distinct immunoprofiles for every carcinoma subtype. Fluorescence in situ hybridization analyses of therapeutic target genes (c-myc, EGFR1, CCND1, HER2) found CCND1 to represent the most frequently amplified gene in our series (7.5%).

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Ampulla of Vater; bcl-2-Associated X Protein; Biomarkers, Tumor; Common Bile Duct Neoplasms; Cyclin D1; Ephrin-B2; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Humans; Immunophenotyping; Keratin-20; Keratin-7; Male; Middle Aged; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-myc; Receptor, ErbB-2; Young Adult

Periampullary cancers, the incidence of which increases gradually with industrialization, still pose a significant challenge to clinicians and researchers. Specifically, the role of cell-cycle proteins and tumor suppressor genes in these cancers is not yet clear. Recent studies have revealed that genes and proteins related to cell cycle and apoptosis regulation may be involved in pancreatic carcinogenesis.. Tissue samples were obtained from patients with periampullary cancers who underwent surgery at the National Taiwan University Hospital without receiving previous chemotherapy or radiation therapy. All periampullary cancer tissue samples were examined by a pathologist, who was unaware of the parameters to be investigated. A total of 68 patients with periampullary cancers (29 ampulla of Vater cancers (AVCs) and 39 pancreatic ductal cancers (PDCs), including various stages and histological subtypes, were enrolled. The relevant demographic and clinicopathological information was obtained from medical records.. Cell-cycle proteins, including p16, Rb, cyclin D1, p53, and E2F1, were analyzed by immunohistochemical staining. Here, significant differences were noted between AVCs and PDCs with regard to the expression of cyclin D1. This corresponded to a poor prognosis in PDCs (P < 0.05); AVCs, on the other hand, showed a relatively high survival rate. There is no obvious statistical difference between the 2 groups with regard to the expression of p16, Rb, p53, and E2F1. The study also revealed that cyclin D1 plays different roles in the carcinogenesis of AVCs and PDCs.. The expression of cyclin D1 is more often correlated with prognosis in AVCs than in PDCs, and may serve as a biomarker for the disease.

Topics: Ampulla of Vater; Biomarkers, Tumor; Chi-Square Distribution; Common Bile Duct Neoplasms; Cyclin D1; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pancreatic Neoplasms; Predictive Value of Tests; Prognosis; Survival Rate

Several studies have reported that dysregulation of beta catenin or k-ras mutation promotes cyclin D1 expression. This study investigated the relation between cyclin D1 expression and clinicopathological parameters in carcinoma of the ampulla of Vater (CAV), and also assessed the relation between increased cyclin D1 expression and beta catenin/k-ras status in this series.. Thirty CAVs were evaluated for cyclin D1 expression by immunohistochemistry in relation to patient clinicopathological features. Aberrant beta catenin expression and k-ras mutation were also investigated by immunostaining and direct sequencing, and related to cyclin D1 expression.. Increased cyclin D1 expression was seen in 17 of 30 CAVs and was significantly correlated with tumour cell proliferation and disease free survival time (p = 0.018, p = 0.018, respectively). Nuclear accumulation of beta catenin was found in nine of 30 cases, including four cases with missense mutations in exon 3 of CTNNB-1, and was significantly correlated with increased cyclin D1 expression (p = 0.003). k-ras gene mutation was detected in 12 of 30 cases, and was also significantly correlated with increased cyclin D1 expression (p = 0.026). Overall, 14 of 17 CAVs with increased cyclin D1 expression showed nuclear accumulation of beta catenin and/or k-ras mutation.. Increased cyclin D1 expression appears to be associated with tumour proliferation and poorer clinical outcome in CAV. It is also associated with both aberrant beta catenin expression and k-ras mutation. These results are consistent with the in vitro data that cyclin D1 can be transactivated by activated beta catenin-T cell factor/LEF and k-ras pathways.

Topics: Aged; Ampulla of Vater; beta Catenin; Biomarkers, Tumor; Common Bile Duct Neoplasms; Cyclin D1; Cytoskeletal Proteins; Disease-Free Survival; Female; Gene Expression; Genes, ras; Humans; Immunohistochemistry; Male; Middle Aged; Point Mutation; Prognosis; Trans-Activators