cyclin-d1 and Carcinoma--Adenosquamous

Colorectal adenosquamous carcinoma (ASC) is exceedingly rare, comprising less than 0.1% of all colorectal malignancies, and is characterized by the admixture of glandular and squamous components. Due to its rarity, immunohistochemical and biological profiles have not been well investigated. The clinico-pathologic features of 29 cases of primary colorectal adenosquamous carcinomas, including four synchronous metastases, as well as the immunohistochemical expression of keratin 20, CDX2, keratin 34βE12, keratin 5/6, p63, p40, β-Catenin, Cyclin D1 and mismatch repair protein (MMR) expression in both squamous and glandular components are described. All ASCs showed aggressive clinico-pathologic features; all cases showed at least one aggressive pathologic characteristic (poorly differentiated, vascular invasion, infiltrative growth pattern) and 69% of cases were either stage III or IV. The squamous component was keratin 34βE12 positive in all cases and keratin 5/6 positive in 27 cases, while only 7 cases showed p63 and/or p40 expression. β-Catenin and Cyclin D1 showed different expression, with nuclear staining of Cyclin D1 in the squamous component of all cases (both primary and metastatic lesions) and nuclear staining of β-Catenin predominantly in the glandular component. All but one case showed proficient MMR profile. Sixteen patients (64%) died of their disease with median survival of 10 months. ASC show aggressive clinical outcome and aggressive pathologic characteristics. A peculiar keratin 34βE12 positive profile in the squamous component is seen differing from squamous cell carcinoma and non-intestinal ASC. The staining patterns for β-Catenin and Cyclin D1 between components, supports a possible divergent clonal evolution of the neoplasm.

Topics: beta Catenin; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Colorectal Neoplasms; Cyclin D1; Humans; Keratin-5

Homeobox gene caudal related homeobox gene 2 (CDX2) is an intestine-specific tumor suppressor gene. This study is intended to investigate the effect of CDX2 expression on cell proliferation and cyclin D1 expression in pancreatic cancer cells.. Four pancreatic ductal adenocarcinoma cell lines (PancQGO-1, BxPC-3, MIAPaCa-2, CFPAC-1), 1 islet carcinoma cell line (QGP-1), and 1 adenosquamous carcinoma cell line (KP-3) were analyzed for CDX1 and CDX2 expression using real-time reverse transcription-polymerase chain reaction and Western blot analysis. Proliferation of pancreatic cancer cells was analyzed using WST-1 assay after CDX2 transfection. Luciferase assay was performed to examine the effects of CDX2 on cyclin D1 transcriptional activity.. CDX2 was expressed at a significantly higher level in QGP-1 cells than in KP-3 cells. Moreover, CDX2 was expressed at a middle level in 4 pancreatic ductal adenocarcinoma cells. Cell proliferation and cyclin D1 mRNA level were inhibited significantly after CDX2 transfection in pancreatic cancer cells. Furthermore, CDX2 inhibited exogenous nuclear factor kappaB-p65-induced luciferase gene expression in a dose-dependent manner. In addition, CDX2 inhibited pGL2HIVD1kappaB2-luciferase activity.. CDX2 might play a role in inhibiting cell proliferation and repressing cyclin D1 transcriptional activity through the proximal nuclear factor kappaB binding site in pancreatic cancer cells.

Topics: Carcinoma, Adenosquamous; Carcinoma, Islet Cell; Carcinoma, Pancreatic Ductal; CDX2 Transcription Factor; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Cyclooxygenase 2; Down-Regulation; Gene Expression Regulation, Neoplastic; Homeodomain Proteins; Humans; NF-kappa B; Pancreatic Neoplasms; Promoter Regions, Genetic; RNA, Messenger; Time Factors; Transcription, Genetic; Transfection

To investigate the expressions of Ep-CAM and cyclin D1 and their correlation with the clinicopathological factors and prognosis in gallbladder carcinoma.. Ep-CAM and cyclin D1 expressions were detected by PV6000 immunohistochemical staining in 60 gallbladder carcinoma and 15 para-cancerous mucosa specimens.. Ep-CAM and cyclin D1 expressions were detected in 56.7% and 48.3% of the cancer tissues, respectively, significantly higher than those in the normal mucosa (P < 0.05). Ep-CAM expression was not correlated with clinicopathological data, however cyclin D1 expression was correlated with pathological differentiation and necrosis (P < 0.05). Survival analysis showed that patients with positive Ep-CAM or cyclin D1 expression had a shorter survival time than that in the patients without (P < 0.05). Moreover, Ep-CAM and cyclin D1 expressions were positively correlated with each other (r = 0.307, P = 0.017).. Ep-CAM or cyclin D1 expression is a unfavorable prognostic factor in gallbladder carcinoma.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Cell Differentiation; Cyclin D1; Epithelial Cell Adhesion Molecule; Female; Gallbladder Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Survival Rate

Because the incidence of adenocarcinoma of the uterine cervix has recently risen, the evaluation of radiotherapy (RT) for this disease has become an increasingly urgent matter. We analyzed the expression of the cell cycle-associated proteins p53, p27, p21/waf1/cip1, and cyclin D1 in cervical adenocarcinomas in correlation with the prognostic significance in tumors treated with RT alone.. The expression of p53, p27, p21/waf1/cip1, and cyclin D1 was studied using an immunohistochemical method in 53 cases of cervical adenocarcinoma treated only with RT. Patients received RT alone between 1965 and 1994. The mean patient age was 61.8 +/- 12.6 years (range, 36-82 years). The number of patients with Stage I, II, III, and IVA disease was 6, 16, 28, and 3, respectively.. The number of patients with p53, p27, p21/waf1/cip1, and cyclin D1 positive tumors was 24, 18, 22, and 8, respectively; no statistically significant correlation was noted. The 5-year disease-free survival rate of p53-positive patients was 30%, significantly lower than the 62% for the p53-negative patients (p = 0.02); no statistically significant correlation was noted between disease-free survival and p27, p21/waf1/cip1, and cyclin D1 expression. No statistically significant correlation was observed between local control and expression of any of the proteins.. Expression of p53 protein has a statistically significant impact on disease-free survival in adenocarcinoma of the uterine cervix treated with RT alone. However, the clinical significance of p27, p21/waf1/cip1, and cyclin D1 protein expression was not obvious.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Adenosquamous; Cell Cycle Proteins; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclins; Female; Humans; Immunohistochemistry; Middle Aged; Multivariate Analysis; Neoplasm Proteins; Survival Rate; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Uterine Cervical Neoplasms

Alterations in expression of the p53 and cyclin D1 genes have been implicated in the development of esophageal carcinomas in both humans and animal models. We hypothesize that altered expression of cyclin D1 and p53 may be involved in the sequential development of esophageal carcinomas with glandular differentiation induced by the carcinogen, 2,6-dimethylnitrosomorpholine (DMNM) in rats with duodenal content reflux esophagitis. In the present study Sprague-Dawley rats were given DMNM 15 days after performing an esophago-jejunostomy in order to induce chronic duodenal content reflux esophagitis. Expression and localization of p53, cyclin D1 and Ki-67 were examined by immunohistochemical analyses. Twenty of 24 animals developed different types of esophageal carcinomas, including pure squamous carcinoma, adenosquamous carcinoma and pure adenocarcinoma. Undifferentiated basaloid areas were frequently observed in these tumors. Cyclin D1 overexpression was observed in hyperplastic lesions and increased through dysplasia and in undifferentiated areas of infiltrating carcinoma. Cyclin D1 expression coincided with increased Ki-67 expression and decreased along with cell differentiation. The p53 immunohistochemical pattern was parallel to that of cyclin D1, although the percentage of positive cells was usually smaller in all lesions and increased p53 expression started at the dysplastic stage. These findings suggest that overexpression of cyclin D1 may be an early event in DMNM-induced rat esophageal tumorigenesis, causing increased proliferation of esophageal stem cells. Abnormal p53 expression may then be required to promote the development of neoplastic transformation from dysplastic epithelium through invasive phenotype, being more evident in cancer cells with squamous differentiation.

Topics: Adenocarcinoma; Animals; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cell Division; Cyclin D1; Duodenogastric Reflux; Esophageal Neoplasms; Esophagectomy; Female; Immunoenzyme Techniques; Jejunostomy; Ki-67 Antigen; Male; Quinoxalines; Rats; Rats, Sprague-Dawley; Tumor Suppressor Protein p53

The purpose of the present study was to define the overexpression of cyclin D1 in superficial and advanced esophageal carcinomas and to investigate whether the expression of this molecule indicates a poor prognosis. This study included 41 patients with superficial esophageal carcinomas (Tis and T1) and 48 patients with advanced esophageal carcinomas (T2, T3, and T4). The expression of cyclin D1 in surgically resected specimens was evaluated immunohistochemically with a monoclonal antibody. Positive immunoreactivity was found in 31 of 89 cases (35%). Overexpression of cyclin D1 did not correlate with TNM classification or histologic type. Of the 48 patients with advanced esophageal carcinomas, 32 patients with cyclin D1-negative tumors survived longer than did 16 patients with cyclin D1-positive tumors (P = 0.0017). In contrast, we observed no survival difference between patients with cyclin D1-positive and -negative superficial esophageal carcinoma. These results suggest that cyclin D1 indicates a poor prognosis in cases of advanced esophageal carcinoma but not in cases of superficial esophageal carcinoma.

Topics: Biomarkers, Tumor; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Carcinosarcoma; Cyclin D1; Esophageal Neoplasms; Esophagus; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis