Oncogenic human papillomavirus (HPV), a causative agent of uterine cervical cancer, has also been detected in head and neck squamous cell cancers, especially in squamous cell carcinomas of the tonsils. However, the true HPV prevalence in normal and neoplasic oropharyngeal mucosa remains uncertain. To determine the prevalence of HPV DNA in normal oropharyngeal mucosa of cancer-free individuals, a study was carried out on 50 Brazilian subjects. PCR was performed to identify HPV DNA in samples from four sites in the oropharynx (tonsils, soft palate, base of the tongue, and back wall of the pharynx). For amplification of the HPV DNA, MY09/11 consensus primers were used, and specific genotypes were identified by dot-blot hybridization or cloning and sequencing. HPV DNA was present in 14.0% of the individuals, and the identified genotypes were 16, 18, 52, and 61. All these types are considered high-risk (HR) HPV. The tonsils and the soft palate were the sites with the highest HPV prevalence. This study shows the prevalence of HR HPV in the oropharynx of normal individuals. However, the prevalence of HPV is still unclear, and if HPV infection in a healthy it is not known individual predisposes to HPV-associated disease such as oropharyngeal cancer. Thus, it is important to assess the prevalence of HPV in cancer-free individuals, in order to compare it with the HPV prevalence in oropharyngeal carcinomas and to attempt to determine the true role of HPV in the development of head and neck squamous cell cancers.
Giant cells tumors of bone (GCTB) are benign in nature but cause osteolytic destruction with a number of particular characteristics. These tumors can have uncertain biological behavior often contain a significant proportion of highly multinucleated cells, and may show aggressive behavior. We have studied differential gene expression in GCTB that may give a better understanding of their physiopathology, and might be helpful in prognosis and treatment. Rapid subtractive hybridization (RaSH) was used to identify and measure novel genes that appear to be differentially expressed, including KTN1, NEB, ROCK1, and ZAK using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry in the samples of GCTBs compared to normal bone tissue. Normal bone was used in the methodology RaSH for comparison with the GCTB in identification of differentially expressed genes. Functional annotation indicated that these genes are involved in cellular processes related to their tumor phenotype. The differential expression of KTN1, ROCK1, and ZAK was independently confirmed by qRT-PCR and immunohistochemistry. The expression of the KTN1 and ROCK1 genes were increased in samples by qRT-PCR and immunohistochemistry, and ZAK had reduced expression. Since ZAK have CpG islands in their promoter region and low expression in tumor tissue, their methylation pattern was analyzed by MSP-PCR. The genes identified KTN1, ROCK1, and ZAK may be responsible for loss of cellular homeostasis in GCTB since they are responsible for various functions related to tumorigenesis such as cell migration, cytoskeletal organization, apoptosis, and cell cycle control and thus may contribute at some stage in the process of formation and development of GCTB.
The incidence of penile cancer varies between populations but is rare in developed nations. Penile cancer is associated with a number of established risk factors and associated diseases including phimosis with chronic inflammation, human papillomavirus (HPV) infection, poor hygiene and smoking. The objective of this study was to identify genes related to this type of cancer. The detection of HPV was analyzed in 47 penile squamous cell carcinoma samples. HPV DNA was detected in 48.9% of penile squamous cell carcinoma cases. High-risk HPV were present in 42.5% of cases and low-risk HPV were detected in 10.6% of penile squamous cell carcinomas. The RaSH approach identified differential expression of Annexin A1 (ANXA1), p16, RPL6, PBEF1 and KIAA1033 in high-risk HPV positive penile carcinoma; ANXA1 and p16 were overexpressed in penile squamous cells positive for high-risk HPVs compared to normal penile samples by qPCR. ANXA1 and p16 proteins were significantly more expressed in the cells from high-risk HPV-positive penile carcinoma as compared to HPV-negative tumors (p<0.0001) independently of the subtype of the carcinoma. Overexpression of ANXA1 might be mediated by HPV E6 in penile squamous cell carcinoma of patients with high-risk HPVs, suggesting that this gene plays an important role in penile cancer.
In addition to improving the performance of the cytological diagnosis of the high-grade squamous intraepithelial lesion, the proposed quality control strategy allows a reflection on the causes of incorrect or conflicting scrutiny.
Abstract:Introduction: Cervical cancer is related to the Human Papillomavirus (HPV). The E7 viral DNA sequence induces the start of DNA synthesis of infected cell, releasing protein p16. The sequence E6 inhibits apoptosis, with prolonged survival of cells heavily damaged and changed, with inhibition of p53 protein and increasing of protein Ki-67. In those injured cells, the molecules are reduced to join the cell membrane, the type E-cadherin. Aim:To study the expression of p16 protein in: normal epithelium cervical, cervical lesions, pre-invasive (CIN) persistent and no persistent lesions and invasive carcinoma of the cervix and to correlate with the expression of Ki-67 and Ecadherin.Patients and Methods: 54 uterine cervix biopsies were selected and submitted to immunohistochemical study, with biomarkers p16, Ki-67 and E-cadherin.Results: 1 CIN I (27.9%) and CIN II (47.9%) had lower expression of p16 than in CIN III (73.5%) and invasive carcinoma (72.7%) (p < 0.0005). For Ki-67, invasive carcinoma (57.8%), had a higher expression when compared to CIN I (35.6%), CIN II (51.9%) and CIN III (40.9%) (p = 0.005). E-cadherin expression in invasive carcinoma (46.2%) was lower than in CIN III (56.0%), CIN II (77.4%) and CIN I (82.2%) (p < 0.0005) and, normal epithelium had the greatest E-cadherin expression (89.1%). In persistent and no persistent CIN there was no difference in the expression of the biomarkers, with p16 presenting p = 0.50, Ki-67, p = 0.91 and the E-cadherin a p = 0.43 value. Conclusions:The use of p16, Ki-67 and E-cadherin biomarkers in cervical biopsies with difficult diagnosis could help in the early diagnosis of malignant lesions and support adequate treatment, 2. There is no association between the diagnosis of the biopsy and the persistence of the cervical lesion and, 3. The used biomarkes don't differentiate between persistent CIN and no persistent lesions.
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