The Impact of Cyclooxygenase-2 and Vascular Endothelial Growth Factor C Immunoexpression on the Prognosis of Penile Carcinoma

Paula, Adriano Augusto Peclat de; Motta, Eliane Duarte; Alencar, Rita de Cássia Gonçalves; Saddi, Vera Aparecida; Silva, Rosana Correa da; Caixeta, Gustavo Nogueira; Netto, J. C. Almeida; Carneiro, Megmar Aparecida dos Santos

doi:10.1016/j.juro.2011.09.027

Cited by 21 publications

(12 citation statements)

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“…In Brazil, the prevalence of HPV in penile carcinoma ranges from 30.5 to 63.1% in paraffin-embedded samples [ 25 – 27 , 46 , 47 , 48 ]. This difference observed in HPV-DNA positivity may be related to the methodology of the studies, the selection of samples (paraffin or cryopreserved), incidence of HPV in the geographical regions, methods of viral detection, and population studied [ 14 , 16 , 24 , 43 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…In Brazil, studies carried out in patients with PC found HPV prevalence ranging between 30.5% and 63.1% in the states of São Paulo and Maranhão, respectively [ 25 , 26 ]. In 2011, an investigation conducted in Goiânia, capital of the State of Goiás in Midwestern Brazil, HPV positivity was found in 43.3% of cases, where 50.9% were HPV16 and 25.5% were HPV-18 [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association with clinic pathological factors

Araújo

Paula

et al. 2018

PLoS ONE

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BackgroundPenile carcinoma (PC) is a rare, highly mutilating disease, common in developing countries. The evolution of penile cancer includes at least two independent carcinogenic pathways, related or unrelated to HPV infection.ObjectivesTo estimate the prevalence, identify HPV genotypes, and correlate with clinicopathological data on penile cancer.MethodsA retrospective cohort study involving 183 patients with PC undergoing treatment in a referral hospital in Goiânia, Goiás, in Midwestern Brazil, from 2003 to 2015. Samples containing paraffin embedded tumor fragments were subjected to detection and genotyping by INNO-LiPA HPV. The clinicopathological variables were subjected to analysis with respect to HPV positivity and used prevalence ratio (PR), adjusted prevalence ratio (PRa) and 95% confidence interval (CI) as statistical measures.ResultsThe prevalence of HPV DNA in PC was 30.6% (95% CI: 24.4 to 37.6), high-risk HPV 24.9% (95% CI: 18.9 to 31.3), and 62.5% were HPV 16. There was a statistical association between the endpoints HPV infection and HPV high risk, and the variable tumor grade II-III (p = 0.025) (p = 0.040), respectively. There was no statistical difference in disease specific survival at 10 years between the HPV positive and negative patients (p = 0.143), and high and low risk HPV (p = 0.325).ConclusionsThe prevalence of HPV infection was 30.6%, and 80.3% of the genotypes were identified as preventable by anti-HPV quadrivalent or nonavalent vaccine. HPV infections and high-risk HPV were not associated with penile carcinoma prognosis in this study.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association with clinic pathological factors

Araújo

Paula

et al. 2018

PLoS ONE

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“…Tumor-associated macrophages (TAMs) perform a major role in the tumor microenvironment by increasing angiogenesis, enhancing tumor cell mobility, and modulating immunotolerance. Both TAMs and TGF-B are found to be associated with VEGF, the expression of which has been demonstrated to be an independent prognostic factor for metastatic progression in penile carcinoma [ 39 ]. Moreover, TAMs have been implicated in establishing pre-metastatic niches, which may have a role as a tumor survival mechanism against systemic chemotherapy [ 35 , 40 ].…”

Section: Macrophage/mdsc Infiltration Patternsmentioning

confidence: 99%

The Immune Microenvironment in Penile Cancer and Rationale for Immunotherapy

Ahmed

Falasiri

Hajiran

et al. 2020

JCM

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Penile cancer is an extremely rare malignancy that accounts for approximately 1% of cancer deaths in the United States every year. While primary penile cancer can be managed surgically, advanced and metastatic forms of the disease require more aggressive management plans with systemic chemotherapy and/or radiotherapy. Despite the meaningful response to systemic treatments, the 2-year progression-free survival and disease-specific survival have shown disappointing results. Therefore, there is a crucial need for alternative treatment options with more favorable outcomes and a lower toxicity profile. There are currently extensive studies of tumor molecular biology and clinical trials with targeted molecular therapies, such as PD-1, PD-L1, and CTLA-4. In this review, we will describe the penile cancer microenvironment, and summarize the rationale for immunotherapy in penile cancer patients.

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“…22,23 The cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), and the epidermal growth factor receptor (EGFR) have been reported having a pivotal role in the establishment and maintenance of both acute and chronic inflammatory conditions, as well as in the etiology of the colorectal, vulva, and PeCa. [24][25][26] The overexpression of these proteins can directly lead to carcinogenesis through the promotion of angiogenesis, cell survival, and proliferation. [27][28][29] Considering the above information, our goal was to determine the genome-wide patterns of copy number alterations in the PeCa and the involvement of genes and specific pathways, likely associated with PeCa infected by high risk (hr) HPV: HPV (TP53 and RB1), inflammation (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes.…”

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Genomic profiling reveals the pivotal role of hrHPV driving copy number and gene expression alterations, including mRNA downregulation of TP53 and RB1 in penile cancer

Macedo

Silva

Nogueira³

et al. 2020

Molecular Carcinogenesis

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The incidence of penile cancer (PeCa) is increasing worldwide, however, the highest rates are reported in underdeveloped countries. The molecular mechanisms that underly the onset and progression of these tumors are still unclear. Therefore, our goal was to determine the genome-wide copy number alterations and the involvement of human papiloma virus (HPV) (TP53 and RB1), inflammatory (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes in patients with PeCa from a high incidence region in Brazil (Maranhão). HPV genotyping was performed by nest-PCR and genome sequencing, copy number alterations (CNAs) by array comparative genomic hybridization and gene copy number status, gene, and protein expression by quantitative polymerase chain reaction, reverse transcriptasequantitative polymerase chain reaction, and immunohistochemistry, respectively.HPV genotyping revealed one of the highest frequencies of HPV reported in PeCa, affecting 96.4% of the cases. The most common CNAs observed were located at the HPV integration sites, such as 2p12-p11.2 and 14q32.33, where Abbreviations: aCGH, array comparative genomic hybridization; CNA, copy number alteration; Cq, quantification cycle; FFPE, formalin-fixed paraffin-embedded; HPV, human papiloma virus;HrHPV, High risk HPV; IHCi, mmunohistochemistry; PCR, polymerase chain reaction; PeCa, penile cancer; qPCR, quantitative polymerase chain reaction; RT-qPCR, reverse transcriptase-quantitative polymerase chain reaction; TMA, tissue microarray. ADAM 6, KIAA0125, LINC00226, LINC00221, and miR7641-2, are mapped. Increased copy number of ERBB3 and EGFR genes were observed in association with COX2 and EGFR overexpression, reinforcing the role of the inflammatory pathway in PeCa, and suggesting anti-EGFR and anti-COX2 inhibitors as promising therapies for PeCa. Additionally, TP53 and RB1 messenger RNA downregulation was observed, suggesting the occurrence of other mechanisms for repression of these oncoproteins, in addition to the canonical HPV/TP53/RB1 signaling pathway. Our data reinforce the role of epigenetic events in abnormal gene expression in HPV-associated carcinomas and suggest the pivotal role of HPV driving CNAs and controlling gene expression in PeCa. K E Y W O R D Scarcinoma of the penis, genomic alterations, human papillomavirus, molecular markers

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The Impact of Cyclooxygenase-2 and Vascular Endothelial Growth Factor C Immunoexpression on the Prognosis of Penile Carcinoma

Cited by 21 publications

References 23 publications

Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association with clinic pathological factors

Human papillomavirus (HPV) genotype distribution in penile carcinoma: Association with clinic pathological factors

The Immune Microenvironment in Penile Cancer and Rationale for Immunotherapy

Genomic profiling reveals the pivotal role of hrHPV driving copy number and gene expression alterations, including mRNA downregulation of TP53 and RB1 in penile cancer

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