A comparative analysis of human papillomavirus types 16 and 18 and expression of p53 gene and Ki-67 in cervical, vaginal, and vulvar carcinomas

Koyamatsu, Yasuko; Yokoyama, Masatoshi; Nakao, Yasuo; Fukuda, Kouichi; Saito, Toshiaki; Matsukuma, Keita; Iwasaka, Tsuyoshi

doi:10.1016/s0090-8258(03)00401-3

Cited by 43 publications

(46 citation statements)

References 20 publications

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“…In this study, the percentage of overall positive samples for Ki67 and p53 was comparable, but Ki67 showed a higher level of intensity. The over-expression of Ki67 correlates with 75% of HPV positive carcinoma, confirming the data obtained on cervical carcinoma (33). Cellular gene modifications (such as p53 mutation and Ki67 over-expression) may be important cofactors for carcinogenesis in penile carcinoma especially associated with HPV infection.…”

Section: Discussionsupporting

confidence: 82%

Detection of Human Papillomavirus DNA, P53 and KI67 Expression in Penile Carcinomas

Gentile

Vicini

Giacomelli

et al. 2006

Int J Immunopathol Pharmacol

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Our study is aimed at evaluating the presence of p53 and Ki67 expression by immunohistochemistry in a series of 11 paraffin-embedded penile carcinomas. We also investigated the presence of Human Papillomavirus (HPV) DNA in these tumours and performed an accurate typing by DNA sequencing on positive samples. Immunohistochemistry (IHC) was performed with the anti-p53 and Ki67 mouse monoclonal antibodies. DNA extracted from small sections of each specimen was submitted to amplification with HPV specific general primers; PCR products ofthe proper length were purified and sequenced. IHC demonstrated nuclear accumulation of mutated p53 and Ki 67 expression in 10/11 tumour samples (90.9%). The prevalence of HPV DNA was 72.7%; the most prevalent type was HPV16. Sequencing analysis revealed the presence of HPV53 (12.5%), HPV18 (25%) and HPV16 (62.5%). Out of the p53 or Ki67 positive carcinomas the percentage ofHPV positives was 80% and 70% respectively. Our results indicate that penile carcinoma is frequently associated to high risk HPV and with diffuse p53 and Ki67 expression.Invasive cancer of the penis is a relatively uncommon disease in Western countries (0.I-0.9 per 100,000 males in Europe and0.7-0.9 per 100,000 males in the USA) whereas the highest incidence occurs in developing countries; in someareasofAsia, Africa and South America the incidence of penile carcinoma is significantly higher, reaching 19per 100,000 males. In these countries, penile carcinoma accounts for as much as 10-20% of male cancer(I). This carcinoma spreads locally to regional lymph nodes which are often surgically treated. This procedure has a high morbidity rate(30-90%) (2); thusthe majorissue in treating penile cancer involves the decision of which patient should or should not be submitted to lymph node. dissection. Many groups have identified prognostic factors for the incidence of lymph node metastases to avoid surgical morbidity such as: tumour thickness, histopathological grade, and venous and lymphatic embolization by neoplastic cells (3).In recent years human Papillomaviruses (HPVs) have been identified as possible etiological agents for the disease but thecorrelationbetweenthe viral DNA presence and the prognosis is stilluncertain (4 human papillomavirus (HPV) in cervical carcinomas and the association between HPV and cervical cancer has now been ascertained to reach 99.7% (5). The overall frequency of HPV DNA detection in carcinoma of the penis is far lower, nonetheless the reported prevalence of HPV is highly variable, from 15% to 70%, depending on the sensitivity of the detection method and on the tumour type (6-8). Moreover, only a few studies have analyzed penile carcinogenesis considering both the HPV status and the histological differentiation.The progress in molecular biology techniques makes it possible to analyse several neoplastic diseases by the identification of oncogene activation and/or tumour suppressor gene inactivation. The tumour suppressor gene p53 is located in the short arm of chromosome 17 and has been implicat...

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Section: Discussionsupporting

confidence: 82%

Detection of Human Papillomavirus DNA, P53 and KI67 Expression in Penile Carcinomas

Gentile

Vicini

Giacomelli

et al. 2006

Int J Immunopathol Pharmacol

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“…Daling JR et al (2002) 16 identified genotypes 6, 11, 16, 18 and 45 in the studied cases of invasive squamous cell carcinoma of the vagina, with HPV16 being the most common (58.3%); Koyamatsu Y et al (2003) 17 and Kiyahu MT et al (1989) 14 identified HPV16 and 18 (the only two genotypes studied), and the most common was also HPV16 (positive in 37.5 and 57% of cases, respectively).…”

Section: Discussionmentioning

confidence: 91%

“…18 These discrepant results allow two possibilities: some authors consider that squamous cell carcinoma of the vagina shares etiopathogenic features with vulvar squamous cell carcinoma 17 (in which one third of cases are related to HPV) and cervical squamous cell carcinoma (in which almost 100% of cases are related to HPV), while others consider that squamous cell carcinoma of the vagina is closely related to cervical squamous cell carcinoma. 19 Our results suggest that, like in vulvar invasive squamous cell carcinoma, invasive squamous cell carcinoma of the vagina occur in two different groups of patients: keratinizing squamous cell carcinoma, more common in older patients (mean age: 73.8 years), and non-keratinizing squamous cell carcinoma, affecting mainly younger patients (mean age: 61.5 years).…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7] In vulvar carcinoma, reflecting the dual pathogenesis of these neoplasms, HPV has been detected in 75-100% of basaloid and warty squamous cell carcinoma and in less than 23% of keratinizing squamous cell carcinoma. [8][9][10][11] There are very few detailed studies of the distribution of HPV in invasive and in situ squamous cell carcinoma of the vagina [12][13][14][15][16][17][18][19] Therefore, it is not known if HPV is implicated in most cases, like in cervical carcinoma, or if there are multiple pathways of carcinogenesis, like in vulvar carcinoma. The aims of our study were to determine the distribution of HPV types in 21 cases of primary invasive squamous cell carcinoma of the vagina and to correlate the presence of HPV with histological subtypes.…”

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confidence: 99%

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HPV DNA detection and genotyping in 21 cases of primary invasive squamous cell carcinoma of the vagina

Ferreira¹,

Martins²,

Félix³

2008

Modern Pathology

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Primary invasive squamous cell carcinoma of the vagina is rare, and the role of human papilloma virus in its pathogenesis remains unclear. The aims of our study were to determine the distribution of human papilloma virus genotypes in 21 cases of primary invasive squamous cell carcinoma of the vagina and to correlate human papilloma virus genotype with histological subtypes. Patients' clinical records were reviewed for demographic data and the stage of the disease. Tumors (n ¼ 21) were classified according to the World Health Organization criteria. Human papilloma virus genotyping (INNO-LiPA HPV Genotyping) was performed in the whole series, and statistical analysis was performed with Fisher's Exact Test and with Student's t-test. The patients' age ranged from 36 to 88 (mean 65) years. Six cases were keratinizing squamous cell carcinoma, and 15 cases were non-keratinizing squamous cell carcinoma (seven non-keratinizing not otherwise specified, three basaloid, and five warty types). The median age of patients with keratinizing squamous cell carcinoma was 73.8 years and that of non-keratinizing squamous cell carcinoma patients was 61.5 years (P ¼ 0.08). Human papilloma virus DNA was detected in 17 cases (81%): 13 non-keratinizing squamous cell carcinoma (87%) and four keratinizing squamous cell carcinoma (67%) (P ¼ 0.31). The human papilloma virus genotypes identified were: 6,11,16,18, 31, 33, 35, 40, and 58, with human papilloma virus 16 DNA the most prevalent (33%). Invasive squamous cell carcinoma of the vagina is frequently associated with human papilloma virus infection, and human papilloma virus 16 is the most common genotype. Although without statistical significance, keratinizing squamous cell carcinoma is more frequent in older patients, whereas non-keratinizing squamous cell carcinoma more frequently affects younger women. All studied histological subtypes are strongly associated with human papilloma virus infection. Keywords: vagina; squamous cell carcinoma; human papillomavirus Human papillomavirus (HPV) has been clearly implicated in the pathogenesis of anogenital tract cancer. It has been detected in 90-100% of cervical squamous cell carcinomas 1-3 and in 70-100% of anal squamous cell carcinoma. [4][5][6][7] In vulvar carcinoma, reflecting the dual pathogenesis of these neoplasms, HPV has been detected in 75-100% of basaloid and warty squamous cell carcinoma and in less than 23% of keratinizing squamous cell carcinoma. [8][9][10][11] There are very few detailed studies of the distribution of HPV in invasive and in situ squamous cell carcinoma of the vagina 12-19 Therefore, it is not known if HPV is implicated in most cases, like in cervical carcinoma, or if there are multiple pathways of carcinogenesis, like in vulvar carcinoma. The aims of our study were to determine the distribution of HPV types in 21 cases of primary invasive squamous cell carcinoma of the vagina and to correlate the presence of HPV with histological subtypes. Materials and methodsWe searched the Department of Pathology database f...

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“…34 We used clone DO-7 p53 antibody, which preferentially detects mutated p53 protein or high levels of wild-type protein. We detected p53 expression in 87% (13/15) of the penile verrucous carcinomas, which was similar to the usual type squamous cell carcinomas, but the percentage of stained cells was low (in most cases only 5-10% of cells stained).…”

Section: Discussionmentioning

confidence: 99%

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

et al. 2009

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Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16 INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16 INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique lowrisk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16 INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16 INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.

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A comparative analysis of human papillomavirus types 16 and 18 and expression of p53 gene and Ki-67 in cervical, vaginal, and vulvar carcinomas

Cited by 43 publications

References 20 publications

Detection of Human Papillomavirus DNA, P53 and KI67 Expression in Penile Carcinomas

Detection of Human Papillomavirus DNA, P53 and KI67 Expression in Penile Carcinomas

HPV DNA detection and genotyping in 21 cases of primary invasive squamous cell carcinoma of the vagina

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

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