Detection of Human papillomavirus and cellular regulators p16INK4a, p53, and NF-κB in penile cancer cases in Kenya

Senba, Masachika; Buziba, Nathan; Mori, Nozomu; Wada, Akihiro; Irie, Sumiko; Toriyama, Kan

doi:10.4149/av_2009_01_43

Cited by 22 publications

(24 citation statements)

References 28 publications

(39 reference statements)

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“…Since p53 inactivating mutations have been observed in PC, the prognostic role of p53 expression in Chinese patients with PC was assessed 12 24 25. Considering the so far published different percentages of p53 overexpression among ethnically different PC study cohorts, it is tempting to speculate that in addition to possible differences in diagnostic criteria used for staining evaluation, geographical or ethnical disparities might be at play 12 26 27…”

Section: Discussionmentioning

confidence: 99%

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis

et al. 2011

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“…To the best of our knowledge, the immunohistochemical localization of NF-κB associated with HPV infection in penile cancer was previously reported using materials obtained from previous studies of Kenya, East Africa and Nagasaki, Japan (16,17). The purpose of this study was to determine the relationship among HPV infection, p16 INK4a , p53 and NF-κB in penile cancer in northern Thailand.…”

Section: Introductionmentioning

confidence: 96%

Relationship among human papillomavirus infection, p16INK4a, p53 and NF-κB activation in penile cancer from northern Thailand

Senba¹,

Mori²,

Fujita³

et al. 2010

Oncology Letters

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Abstract. Human papillomavirus (HPV) E6 and E7 oncoproteins are essential factors for HPV oncogenesis. These E6 and E7 gene products play a central role in the induction of malignant transformation by interacting with several cellular regulatory proteins such as p16 INK4a , p53 and nuclear factor κB (NF-κB). In the present study, conducted in northern Thailand, HPV-DNA was detected in penile cancer cases using an in situ hybridization procedure and p16 INK4a , p53 and NF-κB were detected by immunohistochemistry. Using the cell cycle regulatory proteins p16 INK4a (61.5%) and p53 (71.8%), it was found that of the 51 cases, 39 (76.5%) were HPV-DNApositive in penile cancer. On the other hand, 25% p16 INK4a and 75% p53, respectively, were found in HPV-negative cases. Prevalence of HPV infection (76.5%) was shown in penile cancer cases in northern Thailand. No difference was found between HPV-positive and HPV-negative cases with respect to the presence of the cell cycle regulatory protein p53. On the other hand, p16 INK4a was found to be different between HPV-positive and HPV-negative cases. Inactivation of tumor suppressor genes, such as p16 INK4a and p53, to genetic instability, cell immortalization, accumulation of mutations and cancer formation, with or without HPV and irrespective of HPV infection, is therefore suggested. Of the 39 HPV-positive cases, 35 (89.7%) were NF-κB-positive in the nucleus, 29 (74.4%) in the cytoplasm and 37 (94.9%) in the nucleus and/or cytoplasm. NF-κB was detected in 4 (33.3%) of the 12 HPV-negative cases. Therefore, we propose that penile cancer cases with HPV infection are more likely to activate NF-κB than those without HPV infection.

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“…However, the results vary greatly between 26% and 91% [8,32,36,38,39]. Moreover, correlations between p53 overexpression and HPV status or p53 mutations also display a very heterogenous picture.…”

Section: Discussionmentioning

confidence: 90%

“…Prowse et al detected p16 overexpression in 46% of penile SCCs, which was significantly associated with HPV infection [24]. In contrast, Senba et al described p16 overexpression in an equal amount of HPV-positive and HPV-negative penile carcinomas from Kenya [32].…”

Section: Discussionmentioning

confidence: 93%

Alterations in the tumor suppressor gene p16 INK4A are associated with aggressive behavior of penile carcinomas

Poetsch¹,

Hemmerich²,

Kakies

et al. 2010

Virchows Arch

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Alterations in the p16/cyclinD1/Rb and ARF/Mdm2/p53 pathways are frequent events in the pathogenesis of squamous cell carcinomas. Different mechanisms of p16 regulation have been described for penile carcinomas so far. Therefore, expression of p16 and p53 was immunohistochemically detected with monoclonal antibodies in 52 primary invasive penile squamous cell carcinomas. The carcinomas were analyzed for allelic loss (LOH) in p16(INK4A) and p53, as well as for mutations in the p16(INK4A) and the p53 gene. In addition, we examined the promoter status of p16(INK4A) by methylation-specific PCR. The presence of human papilloma virus (HPV) 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Data were compared to clinical data. Concerning p16, 26 (50%) tumors showed positive immunohistochemistry, 32 (62%) tumors showed allelic loss and 22 tumors (42%) showed promoter hypermethylation. All tumors with negative p16 immunohistochemistry showed LOH near the p16(INK4A) locus and/or hypermethylation of the p16(INK4A) promoter. HPV 16 DNA was detected in 17 tumors, ten of them with positive p16 immunostaining. The remaining seven tumors with negative p16 staining showed allelic loss and/or promoter hypermethylation. Evidence of lymph node metastasis was significantly associated with negative p16 immunohistochemistry as well as with combined LOH and promoter hypermethylation (p = 0.003 and p = 0.018, respectively). Allelic loss around p53 was found in 22 tumors (42%), and seven mutations of the p53 gene could be demonstrated in our tumors. No correlations could be found between any p53 alteration and clinical parameters.

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Detection of Human papillomavirus and cellular regulators p16INK4a, p53, and NF-κB in penile cancer cases in Kenya

Cited by 22 publications

References 28 publications

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis

Relationship among human papillomavirus infection, p16INK4a, p53 and NF-κB activation in penile cancer from northern Thailand

Alterations in the tumor suppressor gene p16 INK4A are associated with aggressive behavior of penile carcinomas

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