p53 as a New Prognostic Factor for Lymph Node Metastasis in Penile Carcinoma: Analysis of 82 Patients Treated with Amputation and Bilateral Lymphadenectomy

Lopes, Ademar; Bezerra, Artur Lício Rocha; Pinto, Clóvis Antônio Lopes; Serrano, Sergio; Mello, Celso Lopes; Villa, Luisa L.

doi:10.1016/s0022-5347(05)64836-7

Cited by 122 publications

(36 citation statements)

References 22 publications

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“…The mutant protein accumulates in the nucleus of tumor cells and is identified by immunohistochemical reaction. The frequency of the overexpression of the p53 protein product was reported to be 41-89% in penile squamous cell carcinomas (8,26,27). Our data showed that overexpression of the p53 protein product was detected in 37 (72.5%) of 51 penile cancer cases with and without HPV infection.…”

Section: Discussionmentioning

confidence: 48%

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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Section: Discussionmentioning

confidence: 48%

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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“…The overall percentage of p53 positive carcinomas is remarkably high (91%) compared to reported values ranging from about 25% to 65% (26)(27)(28)(29)(30). In HPV positive tumours, p53 was detected in 100% of samples, 50% of them having a very strong (group II) estimated intensity.…”

Section: Discussionmentioning

confidence: 66%

“…This method has been used before for detection of mutated p53 in genital and bladder cancer (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

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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“…Therefore, reliable staging information can only be acquired through surgical procedures with subsequent histologic examination of the inguinal lymph nodes. The pathologic factors with known prognostic value, other than the presence of lymph node metastasis, include tumor thickness, grade, histologic type, lymphovascular embolization, presence of koilocytosis and stage (4)(5)(6). On the clinical nodal status there is a dilemma: a significant number of patients with palpable lymph nodes do not have metastasis, in the other hand, 20% of patients with clinically non-suspicious nodes present micrometastasis at pathological examination.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

Ornellas¹,

Ornellas²,

Chinello³

et al. 2012

Int. braz j urol.

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Purpose: To investigate the use of ClinProt technique to identify cancer markers in plasma of patients suffering from squamous cell carcinoma of the penis (SCCP). Materials and Methods: Plasma of 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment between June 2010 and June 2011 was collected and analyzed by the ClinProt/MALDI/ToF technique. Then the peptides were identifi ed from the C8 MB eluted fraction of patients' and control subjects' plasma by LIFT MS/MS. Results: A cluster of 2 peptides (A=m/z 1897.22 ± 9 Da and B=m/z 2021.99 ± 9 Da) was able to discriminate patients from control subjects. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% sensitivity and specifi city, respectively. The cluster also showed very high sensitivity (100%) and specifi city (97%) for SCCP patients that died due to the disease. Furthermore, patients with lymph node involvement presented sensitivity and specifi city of 80% and 97%, respectively. These two peptides were identifi ed by the proteomic approach based on a MALDI-TOF/TOF as fragments of C3 (m/z 1896.17) and C4a/b (m/z 2021.26) complement proteins. Conclusions:The results showed that as the disease progresses, the fragments C3 and C4 A/B are less expressed in comparison with healthy subjects. These results may be useful as prognostic tools.

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p53 as a New Prognostic Factor for Lymph Node Metastasis in Penile Carcinoma: Analysis of 82 Patients Treated with Amputation and Bilateral Lymphadenectomy

Abstract: Immunoreactivity of p53 is an independent factor for lymph node metastasis. The association of positive p53 with positive HPV DNA was related to a worse prognosis.

Cited by 122 publications

References 22 publications

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

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

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

Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

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