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  • Metastasis
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  • 1
    Language: English
    In: International Journal of Molecular Sciences, 01 September 2013, Vol.14(10), pp.19494-19505
    Description: Penile cancer is a rare tumor. There is a limited understanding of the biological mediators of prognostic and therapeutic importance in penile cancer. However, there exists some fundamental understanding of the major pathways involved in the development of penile pre-neoplastic lesions and neoplasms. The aim of the present review is to highlight our current state of molecular knowledge in penile cancer to foster the necessary tools for researchers to pave major advancements in our current treatment paradigms and cancer specific outcomes.
    Keywords: Penile Cancer ; Pathways ; Carcinogenesis ; Progression ; Metastasis ; Biology
    ISSN: 1422-0067
    E-ISSN: 1422-0067
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  • 2
    Language: English
    In: Therapeutic Advances in Urology, June 2012, Vol.4(3), pp.133-138
    Description: Penile cancer is an aggressive disease and after systemic progression it is virtually incurable. While this squamous cell cancer responds to chemotherapy, successful treatment of lymphatic metastases can only be achieved with aggressive surgical treatment in combination with chemotherapy. However, because penile carcinoma is relatively rare there is a paucity of clinical data on the chemotherapy for this aggressive disease. Recent advances have included the establishment of less toxic regimens incorporating taxanes, while cisplatinum remains central to all regimens. Multi-institutional studies are urgently needed to advance the multimodal care for patients with penile cancer.
    Keywords: Penis ; Neoplasm ; Penile Cancer ; Lymph Node ; Metastasis ; Chemotherapy ; Medicine
    ISSN: 1756-2872
    E-ISSN: 1756-2880
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  • 3
    Language: English
    In: Virchows Archiv : an international journal of pathology, February 2011, Vol.458(2), pp.221-9
    Description: 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.
    Keywords: Genes, P16 ; Carcinoma, Squamous Cell -- Genetics ; Penile Neoplasms -- Genetics
    ISSN: 09456317
    E-ISSN: 1432-2307
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  • 4
    Language: English
    In: European Urology, January 2015, Vol.67(1), pp.142-150
    Description: Penile cancer has high mortality once metastatic spread has occurred. Local treatment can be mutilating and devastating for the patient. Progress has been made in organ-preserving local treatment, lymph node management, and multimodal treatment of lymphatic metastases, requiring an update of the European Association of Urology guidelines. To provide an evidence-based update of treatment recommendations based on the literature published since 2008. A PubMed search covering the period from August 2008 to November 2013 was performed, and 352 full-text papers were reviewed. Levels of evidence were assessed and recommendations graded. Because there is a lack of controlled trials or large series, the levels of evidence and grades of recommendation are low compared with those for more common diseases. Penile squamous cell carcinoma occurs in distinct histologic variants, some of which are related to human papilloma virus infection; others are not. Primary local treatment should be organ preserving, if possible. There are no outcome differences between local treatment modes in superficial and T1 disease. Management of inguinal lymph nodes is crucial for prognosis. In impalpable nodes, invasive staging should be done depending on the risk factors of the primary tumour. Lymph node metastases should be treated by surgery and adjuvant chemotherapy in N2/N3 disease. Organ preservation has become the standard approach to low-stage penile cancer, whereas in lymphatic disease, it is recognised that multimodal treatment with radical inguinal node surgery and adjuvant chemotherapy improves outcome. Approximately 80% of penile cancer patients of all stages can be cured. With increasing experience in the management of penile cancer, it is recognized that organ-preserving treatment allows for better quality of life and sexual function and should be offered to all patients whenever feasible. Referral to centres with experience is recommended. Penile preservation should be offered as the primary treatment modality to men with localised penile cancer. Conservative surgery may improve quality of life; however, the risk of local recurrence is higher than after radical surgery (eg, partial penectomy). The management of regional lymph nodes is decisive for long-term patient survival.
    Keywords: Penile Cancer ; Squamous Cell Carcinoma ; Lymph Node ; Invasive Disease ; Metastasis ; Surgery ; Laser ; Chemotherapy ; Reconstruction ; Follow-Up ; Quality of Life ; Guidelines ; European Association of Urology ; Medicine
    ISSN: 0302-2838
    E-ISSN: 1873-7560
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  • 5
    Language: English
    In: Virchows Archiv, 2011, Vol.458(2), pp.221-229
    Description: 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.
    Keywords: Penile carcinoma ; Metastasis ; p16 ; HPV ; LOH
    ISSN: 0945-6317
    E-ISSN: 1432-2307
    Source: Springer Science & Business Media B.V.
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  • 6
    In: Modern Pathology, 2007, Vol.20(10), p.1069
    Description: Penile cancer, observed only rarely in the western world, represents a carcinoma that may be cured by resection of primary lesion and in case of lymph node metastasis by early lymph node dissection. This early inguinal lymphadenectomy bares a significant better survival even in cases of nonpalpable lymph nodes, but carries also a high risk of overtreatment, especially in lower tumor stages. Due to the low incidence, only few data are available on the molecular genetic background of this tumor, especially concerning tumor progression and metastasis. Therefore, we studied 62 microsatellite markers in 28 penile carcinomas searching for markers predicting progression or outcome. LOH in more than 25% of primary tumors was found on six different chromosomes, including 2q, 6p, 8q, 9p, 12q and 17p13. Statistically significant correlations could be established in D6S260 to clinical outcome and in markers from chromosomes 6, 9 and 12 to tumor stage and metastasis. These regions are worthy for further analysis concerning tumor suppressor genes and metastasis suppressor genes.
    Keywords: Medicine ; Biology;
    ISSN: 0893-3952
    E-ISSN: 15300285
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