p16 expression in urothelial carcinoma: Experience from a tertiary care center in coastal South India.

Background: Urothelial carcinomas (UC) account for 6 and 2% of all cancers in men and women, respectively. Human papillomavirus (HPV) is one of the causative agents in cancers of the uterine cervix and head and neck. The role of HPV is also being studied in cancers of the urinary bladder, penis, and prostate. As p16-INK4a is a surrogate marker for high-risk HPVE7 oncoprotein, this study aims to highlight the utility of p16 immunohistochemistry (IHC) in the evaluation of HPV-associated UC. Materials and Methods: A retrospective study was conducted on UC of the bladder received in the Pathology department between January 2013 and December 2018. Bladder biopsies from non-neoplastic lesions served as controls. IHC was done for the detection of the p16 antigen. The p16 staining was recorded as positive, when there was strong staining in >50% of tumor nuclei. The p16 positive and negative tumors were compared based on age, gender, tumor size, grade, and muscle invasion. P value <0.05 was considered statistically significant. Results: The expression of p16 was analyzed in 72 UC and compared with 20 non-neoplastic cases, of which 26.4% of the cases showed p16 expression. The p16 expression was absent in the non-neoplastic lesions. While the majority (87.5%) of the low-grade tumors were negative for p16 expression, 43.8% high-grade tumors were positive. Similarly, a larger proportion of invasive carcinomas (38.8%) expressed p16 as compared to non-invasive carcinomas (13.8%). Thus, p16 expression showed a significant association with grade and stage in these malignancies (P < 0.05). Conclusion: The p16 expression was associated with high-grade and muscle-invasive UC. The p16 was absent in all non-neoplastic and precursor lesions. Thus, it can provide essential information not only about HPV association but also on the prognostic implications for the patients.

Protease inhibitor effects on prevalence of bacterial vaginosis and human papillomavirus-related lesions.

AIM: Antiretrovirals of the protease inhibitor (PI) class tend to achieve low concentrations in biological fluids. This study aimed to analyze possible changes in the vaginal microbiome and frequency of cervical human papillomavirus (HPV)-DNA and HPV-related lesions associated with the use of PI in antiretroviral therapy (ART). METHODS: Eighty-eight women with human immunodeficiency virus infection were divided in two groups: ART with PI and without PI. All the participants underwent anamnesis with demographic data collection. The total DNA, used as the template in the polymerase chain reaction-based assays for the detection of HPV-DNA, was extracted from cervical samples during cervical cytopathology. RESULTS: There were no differences between the groups with respect to HPV-related lesions. Despite the higher prevalence of bacterial vaginosis (BV) in the PI group (33.96% vs 17.14%), the difference was insignificant when considering all women (P = 0.066). When women with a detectable viral load and a CD4+ T-cell count <200 were excluded in both groups, BV was found to be more prevalent in the PI group (odds ratio, 3.349; 95% confidence interval, 1.113-11.41, P = 0.049). No associations were found between BV and age, condom use, cervical HPV, time with current ART regimen, unprotected receptive anal intercourse and cervical HPV-related lesions. CONCLUSION: The use of PI did not alter the frequencies of HPV-DNA and HPV-related lesions. However, an increased frequency of BV was found in women using PI after excluding women with a detectable viral load and a CD4+ T-cell count of <200.

Polymorphism in apoptotic BAX (-248G>A) gene but not in anti-apoptotic BCL2 (-938C>A) gene and its protein and mRNA expression are associated with cervical intraepithelial neoplasia.

HPV is associated with cervical cancer and plays a crucial role in tumor formation. Apoptosis is regulated by different pathways involving genes that either promote (BCL2 gene) or inhibit (BAX gene) cell death. Our goal was to determine whether the BCL2-938C>A (rs2279115) and BAX-248G>A (rs4645878) single nucleotide polymorphisms (SNPs) are associated with squamous intraepithelial neoplasia (SIL) risk, and whether their phenotypic expression was impaired in these lesions. Two hundred and thirty-one cases showing SIL were classified as low SIL (LSIL, n = 101) or high SIL (HSIL, n = 130), and control subjects (n = 266) with no gynecologically proven SIL were recruited. No statistical difference in the genotype and allelic frequency of the BCL-2-938C>A polymorphism was observed among the groups. BCL2-938C/A and A/A homozygotes carriers had higher distribution of BCL-2-expressing cells in stroma in the SIL group. BCL2 mRNA-expression was not correlated with BCL2-938C>A SNPs in both groups. We did find a strong association of the BAX GG genotype and risk for SIL. No difference was observed between LSIL and HSIL groups. In BAX-248G/A and A/A homozygote carriers, the number of BAX-expressing cells was lower the epithelium area in SIL. However, mRNA expression was higher in SIL patients than in the control group. In conclusion, our data provide evidence that allele G carriers in the BAX-248G>A promoter SNP may influence the development of SIL. However, this genotype does not influence the SIL outcome. Additionally, we suggest a possible role of HPV infection in the inhibition of the expression of BAX protein, decreasing cell death, and favoring cervical carcinogenesis.

Higher levels of salivary MUC5B and MUC7 in individuals with gastric diseases who harbor Helicobacter pylori.

OBJECTIVE: The aim of the present study was to assess the salivary levels of MUC5B and MUC7 in individuals with dyspeptic disease and Helicobacter pylori (H. pylori) in the stomach, compared to individuals without dyspeptic disease. METHODS: 30 individuals with dyspeptic disease, who underwent endoscopy for upper gastrointestinal complaints at Hospital Pedro Ernesto-RJ, Brasil and tested positive for H. pylori, and 23 controls with no dyspeptic disease, with mean age 53.5+/-4.4 years, were included in the study. Saliva samples and 3 antral biopsy were taken for PCR analysis and histologic examination. In addition, saliva samples were tested by ELISA with F2 monoclonal antibody and EU7A antibody against MUC7, to determine MUC5B and MUC7 levels, prior to endoscopic examination. The expression pattern of the proteins was quantified by comparison to a pooled saliva sample of 19 healthy volunteers. RESULTS: MUC5B and MUC7 salivary levels were higher in the individuals with dyspeptic disease than in controls (p<0.0001). 33.3% (9/30) of the dyspeptic individuals and 0% of the controls had H. pylori in the oral cavity. CONCLUSIONS: Individuals with gastric diseases, with H. pylori in the stomach, showed higher levels of salivary H. pylori receptors-MUC5B and MUC7-than individuals without gastric diseases. These results suggest that higher levels of specific salivary mucins could be useful as risk indicators for infection by H. pylori.