cyclin-d1 and Polyps

To assess cyclin D1 and PTEN immunoexpression in benign endometrial polyps (EPs) in asymptomatic postmenopausal women and its correlation with obesity.

Topics: Cross-Sectional Studies; Cyclin D1; Female; Humans; Middle Aged; Obesity; Polyps; Postmenopause; PTEN Phosphohydrolase; Uterine Diseases

Little is known about gastric neoplasms arising from hyperplastic polyps (HPs).. To investigate the risk factors associated with neoplasms within HPs and to evaluate the role of alterations of the p16-cyclin D1-pRb pathway in the malignant transformation of HPs.. Retrospective, case-control study.. Tertiary-care center.. Between May 1995 and January 2011, a total of 809 HPs >1 cm were investigated. Associated neoplasms were present in 30 HPs (case group); 30 HPs without neoplasms were selected as a control group.. Gastric polypectomy.. The risk factors associated with neoplasms within HPs and immunohistochemical expression of p16, cyclin D1, p53, and Ki-67 between case and control groups.. Of the 809 HPs, 15 had associated dysplasia, and 15 had carcinoma. Multivariate analysis showed that neoplasm was associated with patient age (odds ratio [OR] 1.159; 95% confidence interval [CI], 1.243-2.044; P < .001), polyp size (OR 1.103; 95% CI, 1.055-1.152; P < .001), and polyp lobulation (OR 4.549; 95% CI, 1.759-11.0766; P < .001) but not with location, multiplicity, intestinal metaplasia, growth pattern, or Helicobacter pylori infection. Loss of p16 expression and high Ki-67 expression were observed in dysplastic areas of HPs compared with the control group (p16 = 14.3% vs 60%; P = .001, Ki-67 = 60.7% vs 36.7%; P < .001). However, no significant differences were found in nondysplastic areas in both groups.. Single-center, retrospective study.. HPs >1 cm may indicate the presence of neoplasms. Loss of p16 and high Ki-67 expression may be markers of HP-associated dysplasia.

Topics: Age Factors; Aged; Carcinoma; Case-Control Studies; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Female; Helicobacter Infections; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Neoplasm Proteins; Polyps; Retrospective Studies; Risk Factors; Stomach Diseases; Stomach Neoplasms; Tumor Burden; Tumor Suppressor Protein p53

Syndromic and sporadic fundic gland polyps are morphologically indistinguishable but may arise via different pathogenetic mechanisms involving mutations of the adenomatous polyposis coli (APC) and its downstream target beta-catenin genes. Although a higher frequency of dysplasia has been reported in syndromic forms, the risk of developing invasive carcinoma is exceedingly low. The current study was designed to investigate whether syndromic and sporadic fundic gland polyps differ in protein expression of a number of genes that are thought to be important in the control of neoplastic transformation. A total of 262 fundic gland polyps, including 155 syndromic polyps obtained from 35 patients with familial adenomatous polyposis or Gardner's syndrome and 107 sporadic polyps randomly selected from 45 patients with gastroesophageal reflux disease or Barrett's esophagus, were included in this study. Immunohistochemical evaluation showed that loss of immunoreactivity to the antibody against the carboxyl terminus of the APC protein, presumably resulting from APC gene mutations, was more frequent in syndromic than in sporadic cases (40% versus 6.7%, P<0.001). However, immunostaining failed to show aberrant nuclear localization of beta-catenin, a protein regulated by APC, in any of the polyps, irrespective of syndromic or sporadic types. Instead, positive membranous staining for beta-catenin was observed in all the cases. In addition, the expression characteristics of 2 other proteins, c-Myc and cyclin D1, whose genes have been reported to be transcriptionally regulated by the APC/beta-catenin pathway, were similar in these two types of polyps. Furthermore, all cases, including those harboring dysplasia, showed negative nuclear staining for p53 and positive nuclear staining for retinoblastoma (RB). Taken together, these data show a lack of dysregulation in the APC/beta-catenin signaling pathway and in the expression of p53 and RB in fundic gland polyps despite a high frequency of somatic mutations of the APC and beta-catenin genes reported in these polyps. These findings may explain at least in part why fundic gland polyps show a negligible malignant potential even in the presence of dysplasia.

Topics: Adenomatous Polyposis Coli Protein; Adolescent; Adult; Aged; beta Catenin; Biomarkers, Tumor; Cell Nucleus; Cyclin D1; Cytoskeletal Proteins; Female; Gastric Fundus; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Proteins; Polyps; Proto-Oncogene Proteins c-myc; Retinoblastoma Protein; Stomach Neoplasms; Syndrome; Trans-Activators; Tumor Suppressor Protein p53

To investigate tumorigenesis in the gastric hyperplastic polyp (HP), we evaluated 19 HPs with and 50 HPs without dysplasia (including carcinoma in situ), as compared with normal mucosa and fundic gland polyps. Helicobacter pylori density was highest in HPs without dysplasia. Apoptotic activity and Ki-67 and p53 expression also were higher in dysplasia in HPs than in normal mucosa, fundic gland polyps, or HPs themselves. The p21WAF1/CIP1 and cyclin D1 levels, in contrast, were highest in HPs. In HPs without dysplasia, size was correlated positively with the degree of stromal inflammation and with p53 and cyclin D1 expression. p53 and c-Ki-ras mutations were detected in 41% (8/19) and 5% (1/19) of dysplasia (including carcinoma in situ) in HPs. Our results demonstrate that the HP enlarges with enhanced cell turnover and overexpression of p53, p21WAF1/CIP1, and cyclin D1, associated with H pylori-related inflammation, and that p53 but not c-Ki-ras mutations may have an important role in dysplastic change in HPs.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Carcinoma in Situ; Cell Transformation, Neoplastic; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; DNA, Neoplasm; Down-Regulation; Female; Helicobacter pylori; Humans; Hyperplasia; Immunoenzyme Techniques; Ki-67 Antigen; Male; Middle Aged; Mutation; Polymerase Chain Reaction; Polyps; Proto-Oncogene Proteins p21(ras); Stomach Neoplasms; Tumor Suppressor Protein p53

The tumor suppressor SMAD4, also known as DPC4, deleted in pancreatic cancer, is a central mediator of TGF-beta signaling. It was previously shown that mice homozygous for a null mutation of Smad4 (Smad4-/-) died prior to gastrulation displaying impaired extraembryonic membrane formation and endoderm differentiation. Here we show that Smad4+/- mice began to develop polyposis in the fundus and antrum when they were over 6 - 12 months old, and in the duodenum and cecum in older animals at a lower frequency. With increasing age, polyps in the antrum show sequential changes from hyperplasia, to dysplasia, in-situ carcinoma, and finally invasion. These alterations are initiated by a dramatic expansion of the gastric epithelium where Smad4 is expressed. However, loss of the remaining Smad4 wild-type allele was detected only in later stages of tumor progression, suggesting that haploinsufficiency of Smad4 is sufficient for tumor initiation. Our data also showed that overexpression of TGF-beta1 and Cyclin D1 was associated with increased proliferation of gastric polyps and tumors. These studies demonstrate that Smad4 functions as a tumor suppressor in the gastrointestinal tract and also provide a valuable model for screening factors that promote or prevent gastric tumorigenesis.

Topics: Age Factors; Animals; Cyclin D1; DNA-Binding Proteins; Genes, Tumor Suppressor; Haploidy; Loss of Heterozygosity; Mice; Polyps; Smad4 Protein; Stomach Neoplasms; Trans-Activators; Transforming Growth Factor beta

Lymphomatous polyposis (LP) is a subtype of non-Hodgkin's lymphoma manifested by numerous polyps affecting long segments of the gastrointestinal tract. The malignant cells of LP often share morphological and immunophenotypic similarity with cells of nodal-based mantle cell lymphoma. Recent genetic studies have shown that mantle cell lymphomas frequently possess a characteristic translocation of the JH/bcl-1 loci. In this study, polymerase chain reaction (PCR) and Southern blot analysis were used to show the presence of JH/bcl-1 translocation in a typical case of LP of the gastrointestinal tract. This provides strong molecular evidence for a biologic link between LP and mantle cell lymphoma. The findings also imply that detection of this translocation may be useful in the diagnosis of morphologically equivocal gastrointestinal biopsy specimens.

Topics: Base Sequence; Biopsy; Blotting, Southern; Cyclin D1; DNA Primers; DNA Probes; DNA, Neoplasm; Gastrointestinal Neoplasms; Humans; Immunoglobulin Heavy Chains; Immunophenotyping; Lymph Nodes; Lymphoma, Non-Hodgkin; Male; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; Polyps; Proto-Oncogene Proteins; Translocation, Genetic