P16 Expression in Squamous Cell Carcinomas of Cervix and Bladder

Cioffi-Lavina, Maureen; Chapman-Fredricks, Jennifer R.; Gomez‐Fernandez, Carmen; Ganjei‐Azar, Parvin; Manoharan, Murigesan; Jordà, Mercè

doi:10.1097/pai.0b013e3181d2bbd7

Cited by 20 publications

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“…55,56 While strong and diffuse cytoplasmic and nuclear p16 expression has been shown to correlate well with HPV status in the cervix [57][58][59] and vulva, 60 it does not appear to have the same predictive value in bladder carcinomas. Cioffi-Lavina et al 61 have shown p16 overexpression in 14 out of 38 cases (37%) of bladder squamous cell carcinoma. It is likely that other, non-HPV-related mechanisms are responsible for upregulation of p16 in these cases.…”

Section: Discussionmentioning

confidence: 96%

Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection

et al. 2012

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Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries endemic to Schistosoma parasitic infections. Unlike squamous tumors of the uterine cervix or oropharynx, the human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. We report on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of selfcatheterization with tumors that tested positive for HPV by in situ hybridization. A retrospective review of our institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the setting of neurogenic bladder. Review of these cases showed the more common welldifferentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder; however, this is the first report of squamous tumors arising in the setting of concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas with a basaloid, poorly differentiated appearance and little to no keratin formation. Modern Pathology (2012) 25, 1534-1542; doi:10.1038/modpathol.2012.112; published online 6 July 2012 Keywords: HPV; neurogenic bladder; squamous cell carcinoma; urothelial cancerThe human papillomavirus (HPV) has an important role as a human carcinogen, with an estimated 10% of cancers worldwide attributed to it. 1 HPV is a small circular double-stranded DNA virus with more than 100 different types described to date. 2 The potential of the virus to cause malignant or benign lesions dictates its classification into low-risk (6,11,40,42, and so on) or high-risk (16,18,31,33,45,51, and so on) types. The prototypical model for carcinogenesis is squamous cell carcinoma of the uterine cervix, in which nearly all such carcinomas are associated with HPV infection. 3,4 The oncogenic role of HPV is also well established for a subset of squamous cell carcinomas in the vulva, 5 penis, 6 anus, 7 and oropharynx. 8 The possible role of HPV infection in bladder tumors has not been completely elucidated as HPV detection rates vary widely from 0 to 100%, depending on the study. 9,10 An intriguing issue has been the possible association of the virus with bladder squamous cell carcinoma. The few published studies 11-14 on this relationship have shown a low frequency of HPV detection, implying that HPV is not likely to have a major role in the development of bladd...

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Section: Discussionmentioning

confidence: 96%

Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection

et al. 2012

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“…3 Detection of HR-HPV by the in situ hybridization method was negative in all cases (0 of 14) ( Figure 1, C and D). The presence of HR-HPV DNA was detected, however, in 3 of 14 cases (21.4%) in which the Cervista HPV HR screening test was used (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…With these selection criteria, 38 cases of primary bladder SCC were identified. These cases were studied in our previous work, in which 14 (37%) were found to be diffusely positive for p16 (Dako M7247, 1:50; clone 484, Dako, Carpinteria, California) by immunohistochemical testing 3 ( Figure 1, B). Specimen types included transurethral resections and cystectomy specimens and were derived from both males (8 cases) and females (6 cases).…”

Section: Methodsmentioning

confidence: 99%

“…In a recent study, 3 we reported that more than one-third (37%) of primary SCCs of urinary bladder demonstrate diffuse p16 immunoreactivity independent of sex or tumor differentiation. From this study, we concluded that in tumors involving the pelvic cavity, the presence of p16 immunoreactivity alone cannot be used to distinguish between tumors of gynecologic or urothelial origin.…”

Section: Commentmentioning

confidence: 99%

“…3 The association between the presence of HPV oncoprotein E7 and the subsequent overexpression of the p16 protein by infected cells has led to the widespread use of immunohistochemical positivity for p16 as an indicator of HPV infection, particularly types 16 and 18. However, p16 overexpression has also been identified in other neoplasms that have not been shown to be HPV related, including dermatofibrosarcoma protuberans, gastric adenocarcinomas, serous endometrial carcinomas, and Hodgkin and non-Hodgkin lymphomas.…”

Section: Commentmentioning

confidence: 99%

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High-Risk Human Papillomavirus DNA Detected in Primary Squamous Cell Carcinoma of Urinary Bladder

Chapman-Fredricks

Cioffi-Lavina

Accola

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-We reported previously that more than onethird (37%) of primary bladder squamous cell carcinomas (SCCs) demonstrate diffuse p16 immunoreactivity independent of gender. This observation made us question whether p16 overexpression in bladder carcinoma is due to human papillomavirus (HPV)-dependent mechanisms.Objective.-To determine whether the presence of highrisk HPV (HR-HPV) DNA could be detected in these tumor cells.Design.-Fourteen cases of primary bladder SCC, which were positive for p16 by immunohistochemistry, were probed for the detection of HR-HPV by in situ hybridization and the signal amplification Invader assay. Samples positive for detection of HR-HPV by Invader assay were amplified by using HR-HPV type-specific primers, and amplification products were DNA sequenced.Results.-Detection of HR-HPV by the in situ hybridization method was negative in all cases (0 of 14). However, in 3 of 14 cases (21.4%), the presence of HR-HPV DNA was detected with the Cervista HPV HR Invader assay, which was followed by identification of genotype. All positive cases were confirmed by using HR-HPV typespecific amplification followed by DNA sequencing. Identified HR-HPV genotypes included HPV 16 (2 cases) and HPV 35 (1 case).Conclusions.-High-risk HPV DNA is detectable in a subset of primary bladder SCCs. Based on the welldocumented carcinogenic potential of HR-HPV, there is a necessity for additional studies to investigate the role of HR-HPV in bladder carcinogenesis.(Arch Pathol Lab Med. 2013;137:1088-1093; doi: 10.5858/arpa.2012-0122-OA) B ladder cancer is the second most common malignancy of the genitourinary tract diagnosed in the United States 1 with approximately 70 000 newly diagnosed cases and 14 000 deaths from disease annually. To date, wellestablished risk factors for the development of bladder squamous cell carcinoma (SCC) include increasing age (peak incidence at 50-70 years), male sex (male to female ratio, 3:1), smoking, exposure to carcinogenic chemicals, and chronic bladder inflammation and/or repeated urinary infections, and molecular/genetic factors. Although the oncogenic role of human papillomavirus (HPV) has been well documented in many epithelial cancers, including most cervical carcinomas, anogenital cancers, and carcinomas of the head and neck, its role in bladder carcinogenesis has been controversial throughout the literature.In gynecologic malignancies, the presence of high-risk HPV (HR-HPV) is often associated with overexpression of p16 protein. Immunohistochemistry for p16 is therefore used to screen for the presence of HR-HPV in primary cervical carcinomas.2 In a recent study, 3 we reported that more than-one third (37%) of primary bladder SCCs demonstrated diffuse p16 immunoreactivity independent of gender or tumor differentiation. From this study, we concluded that in tumors involving the pelvic cavity, the presence of p16 immunoreactivity alone cannot be used to distinguish tumors from gynecologic or urothelial origin. Our observed p16 overexpression in a significant proportion of...

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Urinary Bladder and Urachus

Wilkerson

Liu

2015

Handbook of Practical Immunohistochemistry

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P16 Expression in Squamous Cell Carcinomas of Cervix and Bladder

Cited by 20 publications

References 11 publications

Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection

Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection

High-Risk Human Papillomavirus DNA Detected in Primary Squamous Cell Carcinoma of Urinary Bladder

Urinary Bladder and Urachus

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