The Expression Patterns of p53 and p16 and an Analysis of a Possible Role of HPV in Primary Adenocarcinoma of the Urinary Bladder

Abstract

BackgroundPrimary adenocarcinoma of the urinary bladder is rare. The molecular and cellular events leading to its pathogenesis are not well delineated. The goal of this study was to investigate p53 and p16 expression, as well as HPV status, in a relatively large series of primary bladder adenocarcinomas.Materials and MethodsThirty six cases of urinary bladder adenocarcinoma were chosen from participating institutions. The diagnosis and available clinical history were reviewed in each case. Immunostains for p53, p16 and HPV and high-risk and low-risk HPV-ISH were performed on all tumors.ResultsPatients had an average age of 61 years with a male predominance (1.5∶1 male∶female ratio). The average tumor size in cystectomy specimens was 4.3 cm. Of the cases managed by transurethral resection, 40% were pT2 at the time of diagnosis. In cystectomy specimens, 77% were either pT3 or pT4. Strong nuclear p16 expression was seen in 67% of all cases and p53 expression was present in 58% of the cases. Expression of both markers was seen in 33% of cases. Expression of p16 or p53 alone was present in 12 (33%) and 9 (25%) cases, respectively. Neither marker was expressed in only 3 (8%) of the tumors. No significant correlation between clinical variables and any of the markers we studied was identified. No HPV infection was detected in any case.ConclusionsExpression of p53 and/or p16 is very common in urinary bladder adenocarcinoma. These findings implicate a high likelihood that alterations in these cell cycle proteins contribute to the pathogenesis of these tumors. Despite frequent immunohistochemical labeling for p16, no evidence of HPV infection was found.

Risk Stratification of Early Stage Oral Tongue Cancers Based on HPV Status and p16 Immunoexpression

“…Previous studies have shown p16 expression independent of HPV infection to be associated with epithelial to mesenchymal transitions mediated by MAPK pathway (Steinestel et al, 2013). Our report is also similar to recent studies showing the possibility of p16 overexpression without HPV presence in tumours concluding that it need not always be interpreted as a defacto HPV marker (Alexander et al, 2014;Kim et al, 2014). Our results are in contrast to findings reported by Konig et al, suggesting that p16 immunostaining is to be applied as a pre-screening method for HPV subtyping and that p16 IHC correlates with high risk HPV status (Konig et al, 2007).…”

p53 expression but not p16INK4A correlates with human papillomavirus-associated esophageal squamous cell carcinoma in Kazakh population

“…The use of p16 INK4A immunohistochemical analysis as a surrogate marker of HPV infection in squamous cell carcinoma of the cervix, vagina, and oropharynx has been supported by many studies in recent years [ 15 , 17 , 28 – 30 ]. The p16 INK4A expression is indicative of high risk HPV infection in cancers of squamous cell origin [ 31 ]. In our study, patients with p16 INK4A overexpression have a better prognosis, are correlated with less lymph node metastasis ( p = 0.038), and are frequently associated with lower-grade TNM stage ( p = 0.147), which are in accordance with previous studies [ 21 , 26 , 32 ].…”

Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot

“…Interestingly, p16INK4a overexpression is common in different histological subtypes of bladder cancer including adenocarcinoma (67 %), urothelial carcinoma with squamous differentiation (45.7 %), high-grade urothelial cancers (85.9 %) and urothelial CIS (92.6 %). However, contrary to gynecological tumors, p16INK4a is not a surrogate marker for evidence of HPV infection in bladder cancer [6,[16][17][18].…”