cyclin-d1 and Papilloma--Inverted

Sinonasal inverted papilloma (IP) is a rare and benign epithelial tumor in the sinonasal tract. Recent study suggested the potential role of chronic inflammation in the pathogenesis of IP. This study aims to compare the inflammatory pattern, the capacity of epithelial cell proliferation and. Sixteen patients with unilateral IP and contralateral nasal polyps (NP) were identified through a retrospective chart review. The neutrophil and eosinophil infiltration in IP and NP were assessed by immunostaining for neutrophil elastase and major basic protein (MBP). Immunohistochemistry was also used to assess the expression of FoxM1, Ki67 and cyclin D1 in IP tissue and contralateral NP. Sanger sequencing was used to evaluate the. The neutrophil count in IP was significantly higher than contralateral NP and 68.8% patients presented with neutrophilic inflammation, whereas only 37.5% contralateral NP tissue showed neutrophilic inflammation. The percentage of positive FoxM1-staining cells was significantly increased in IP, and positively correlated with the percentage of cells with positive staining for cyclin D1 and ki67 as well as neutrophil counts.. Our study demonstrated distinct inflammatory pattern between IP and contralateral NP and implied the oncogenic role of neutrophils in the pathogenesis of IP.

Topics: Cell Proliferation; Cyclin D1; Humans; Inflammation; Ki-67 Antigen; Nasal Polyps; Neutrophil Infiltration; Nose Neoplasms; Papilloma, Inverted; Paranasal Sinus Neoplasms; Retrospective Studies

To better understand the pathogenesis of nasal polyps (NPs) and sinonasal inverted papillomas (SIPs), we aimed to establish cell lines from fresh tissues of NPs and SIPs and characterize them. Primary cell cultures were obtained from two NP tissues (NP2 and NP3) and one SIP tissue (IP4). All the cells were polygonal in shape, expressed cytokeratin 14, and had normal diploid chromosome status. HPV58 DNA was detected in NP3. To obtain immortal primary cells, NP2 and IP4 cells were transduced with a combination of mutant CDK4, cyclinD1 and TERT. These cells were thereafter named NP2/K4DT and IP4/K4DT, respectively. HPV58-positive NP3 cells were transduced with TERT alone, the resulting cells named NP3/T. Phenotypic and genotypic identity of original tissues and derived cells was investigated. All the cell cultures with transgenes were confirmed to be derived from their parental cells and primary tumor tissues by analysis of short tandem repeats (STR) and maintained in vitro growth, genetic profiles and gene expression characteristics of the primary cells. These virtually immortalized cells, as well as the primary cells, have potential as in vitro models for studying the pathogenesis of NPs and SIPs and for preclinical study to develop new therapeutic agents.

Topics: Adolescent; Aged; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Child; Cyclin D1; Cyclin-Dependent Kinase 4; Humans; Male; Microsatellite Repeats; Nasal Polyps; Nose Neoplasms; Papilloma, Inverted; Telomerase; Transduction, Genetic

The purpose of this study was to investigate roles of human papillomavirus (HPV) infection and stathmin in sinonasal inverted papilloma (SNIP).. HPV DNA detection was performed by the fluorescence-based polymerase chain reaction (PCR) method. Stathmin protein expression was investigated by the immunohistochemistry method and mRNA expression of stathmin, Kif2a, and cyclin D1 were assessed by real-time PCR in SNIP and control subjects.. The positive rate of HPV DNA detected in SNIP was about 53.6% (15 of 28). Recurrent cases showed a higher rate of HPV infection compared with initial cases and higher Krouse stage (T3 + T4) cases showed higher rate of HPV infection than lower Krouse stage (T1 + T2) cases. Stronger expression of stathmin, Kif2a, and cyclin D1 were observed in SNIP, especially HPV(+) SNIP.. HPV infection was closely associated with recurrence and progression of SNIP. Stathmin is a valuable prognostic marker and could be considered as a therapeutic target in patients with SNIP.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Cyclin D1; DNA, Viral; Female; Humans; Immunohistochemistry; Kinesins; Male; Middle Aged; Nasal Mucosa; Neoplasm Recurrence, Local; Nose Neoplasms; Papilloma, Inverted; Papillomaviridae; Papillomavirus Infections; Paranasal Sinus Neoplasms; Polymerase Chain Reaction; RNA, Messenger; Stathmin; Up-Regulation; Young Adult

The role of human papillomavirus (HPV) in sinonasal inverted papillomas (IPs) is controversial. Determining the prevalence of HPV infection and its impact on the molecular biology of these tumors is critical to characterizing its role in the pathogenesis of IPs.. A total of 112 paraffin-embedded IPs from 90 patients were studied. A tissue microarray was constructed and stained for p16, p53, epidermal growth factor receptor (EGFR), and cyclin D1. HPV presence and types were determined using PGMY 09/11 primers and integration using HPV 11 detection of integrated papillomavirus sequences by ligation-mediated polymerase chain reaction (DIPS-PCR).. HPV was detected in 11 of 90 (12%) patients. HPV 11 was found in 9 samples. HPV 6 and HPV 27 were found in 1 sample each. EGFR staining proportion was higher in HPV-positive IPs vs HPV-negative specimens (56.2% vs 23.6%; p = 0.009). Differences in p16, p53, and cyclin D1 staining were not significant. HPV-positive lesions tend to progress to malignancy (p = 0.064). Three samples were analyzed for integration. Viral integration was found in both malignant tumors but not in the precursor IP.. Degradation of p53 and p16/cyclin D1 dysregulation are not important mechanisms in low-risk HPV-related IP. The low prevalence of HPV in this series indicates it is not a main etiological factor for IPs; however, when present, low-risk HPV may contribute to the biology of IPs through an increase of EGFR expression and a predisposition for malignant progression by integration into the cellular genome.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Disease Progression; DNA, Viral; ErbB Receptors; Female; Human papillomavirus 11; Humans; Immunohistochemistry; Male; Neoplasm Proteins; Neoplasm Recurrence, Local; Papilloma, Inverted; Papillomavirus Infections; Paranasal Sinus Neoplasms; Polymerase Chain Reaction; Tumor Suppressor Protein p53

The aim of this study was better characterize the staining patterns of inverted papilloma (IP) with and without carcinoma by performing immunohistochemistry for p16, epidermal growth factor receptor (EGFR), p53, and cyclin D1 antibodies in a large patient cohort.. A total of 162 IP specimens were collected from 147 patients treated at the University of Michigan between 1996 and 2011. Twenty-two specimens contained carcinoma. Tumor was extracted for construction of 2 tissue microarrays and stained for p16, EGFR, p53, and cyclin D1. Tumor staining intensity and percentage staining were scored.. Benign disease was positive for p16 in 64%, EGFR in 50%, p53 in 30%, and cyclin D1 in 76%. IP with carcinomatous degeneration was positive for p16 in 14%, EGFR in 71%, p53 in 62%, and cyclin D1 in 76%. The differences in staining positivity between benign and malignant disease reached significance for p16 and p53 only. Mean percentage staining by tumor surface area for IP and IP with carcinoma was 12% vs 7% for p16 (no statistical significance [NS]), 20% vs 34% for EGFR (NS), 4% vs 24% for p53 (p < 0.001), and 17% vs 21% for cyclin D1 (NS).. Important characteristic staining pattern for IP with and without carcinoma are highlighted in this study. Unlike recent trends in human papilloma virus (HPV)-related head and neck malignancies, low expression of p16 is a marker for malignancy in this series. Positive staining for p53 correlates with the development of carcinoma in IP.

Topics: Cyclin D1; ErbB Receptors; Genes, p16; Genes, p53; Humans; Papilloma, Inverted; Paranasal Sinus Neoplasms

Human papilloma virus (HPV) was associated with sinonasal inverted papilloma (SIP) in 14/20 (70%) patients with a prevalence of HPV 6/11; alterations of the cell cycle proteins were statistically significant.. We investigated SIPs relationships between HPV infection and aberrant expression of cell cycle proteins.. Twenty SIPs were evaluated for p53, p16(INK4a), pRb, p21(WAF1), p27(Kip1), cyclin D1 and Ki-67 expression by immunohistochemistry. HPV was investigated by polymerase chain reaction (PCR).. HPV DNA was detected in 14/20 patients with inverted papillomas (IPs) (70%). The majority of tumours showed strong p16, p21, p27, pRb and cyclin D1 staining and little or no p53 expression. Tumours harbouring dysplasia were significantly more likely to be p53-positive and exhibit up-regulated p21 and p27, and showed altered intensity and distribution of reactive cells into and through the epithelium. Dysplastic epithelium was strongly reactive for p16 and the MIB 1 labelling index was almost 20%. These findings were associated with expression of p53 in the same zones. Comparing the p53 reactivity with the presence of HPV DNA, SIPs were stratified as follows: HPV + p53-, 12 (63.15%); HPV + p53+, 2 (10.52%); HPV - p53+, 3 (15.78%) and HPV - p53-, 2 (10.52%). Statistical analysis showed that HPV presence correlated with p53-positive immunostaining (p=0.045).

Topics: Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; DNA Probes, HPV; Gene Expression Regulation; Gene Expression Regulation, Viral; Humans; Intracellular Signaling Peptides and Proteins; Ki-67 Antigen; Nose Neoplasms; Papilloma, Inverted; Papillomaviridae; Papillomavirus Infections; Paranasal Sinus Neoplasms; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Salivary Proline-Rich Proteins; Tumor Suppressor Protein p53

It was the aim of this study to assess the expression of selected cell cycle regulation genes in urothelial and sinonasal inverted papillomas (IP).. Archived surgically resected specimens from 18 urothelial and 19 sinonasal IP were studied immunohistochemically for p16, p53, cyclin D1 and Ki67. Staining results were semiquantified and compared between IP and adjacent control mucosa (CM).. p53 expression did not differ between sinonasal and urothelial IP. Although there was a trend of higher p53 expression in IP compared with the adjacent CM in sinonasal and urothelial specimens, this trend failed to be statistically significant. p16 expression was significantly higher in urothelial IP and CM in comparison with their sinonasal counterparts, but did not differ significantly between IP and its adjacent CM either in urothelial or sinonasal specimens. There were no significant differences in the mean scores for cyclin D1 or Ki67.. The changes in p53 expression seen in both types of IP compared with adjacent CM suggest that sinonasal and urothelial IP may share some common ground in terms of their evolution. Although p16 appears not to be directly involved in the development of sinonasal or urothelial IP, the differing recurrence patterns of sinonasal versus urothelial IP may be attributable in part to different p16 expression.

Topics: Adult; Aged; Biomarkers, Tumor; Cell Cycle Proteins; Cyclin D1; Female; Humans; Ki-67 Antigen; Male; Middle Aged; Papilloma, Inverted; Paranasal Sinus Neoplasms; Retrospective Studies; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms; Urothelium

To investigate the clinicopathlogical significance of cyclinE, cyclinD1, P21WAF1/CIP1 and P27KIP1 expression in squamous cell carcinoma of maxillary sinus.. The expression of cyclinE, cyclinD1, P21WAF1/CIP1 and P27KIP1 was examined by the method of immunohistochemistry in inflammatory mucosa of maxillary sinus(10), inverting papilloma of maxillary sinus(20) and squamous cell carcinoma of maxillary sinus (50).. (1) In inflammatory mucosa, inverting papilloma and squamous cell carcinoma, the positive immunostaining rates of cyclinD1 protein were 10.0%, 25.0%, 48.0% respectively (P < 0.05); cyclinE protein was 20.0%, 35.0%, 58.0% respectively (P < 0.05); P21WAF1/CIP1 protein was 80.0%, 65.0%, 40.0% respectively (P < 0.05) and P27KIP1 protein was 70.0%, 75.0%, 40.0% respectively (P < 0.05). (2) There was no significance between the clinical type, T stage and clinical stage of carcinoma of maxillary sinus and the expression of cyclinD1, cyclinE, P21WAF1/CIP1 and P27KIP1 (P > 0.05). (3) P21WAF1/CIP1 positive expression in highly, moderately and poorly differtiated carcinomas were 73.2% (11/15), 58.9% (11/19), 25.0% (4/16) respectively (P < 0.05).. (1) With the development of the lesion, the positive immunostaining rate of cyclinE and cyclinD1 protein increases, while the rate of P21WAF1/CIP1 and P27KIP1 protein decreases. (2) P21WAF1/CIP1 expression is associated with tumour cell differentiation. (3) The mutual mechenism of cell cycle regulators plays an important role in the squamous cell carcinoma of maxillary sinus. The quantity and the frequency of four kinds of gene expression increase with the progression of maxillary sinus carcinogenesis.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Cell Cycle Proteins; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclins; Female; Humans; Immunohistochemistry; Male; Maxillary Sinus; Maxillary Sinus Neoplasms; Middle Aged; Papilloma, Inverted; Tumor Suppressor Proteins