<i>PIK3CA, HRAS</i>
            and
            <i>KRAS</i>
            Gene Mutations in Human Penile Cancer

Andersson, Patiyan; Kolaric, Aleksandra; Windahl, Torgny; Kirrander, Peter; Söderkvist, Peter; Karlsson, Mats G.

doi:10.1016/j.juro.2007.12.040

Cited by 46 publications

(36 citation statements)

References 17 publications

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“…Andersson et al identified mutations of PIK3CA in 8/28 penile tumors (29%) (Andersson et al 2008). Lopez-Knowles identified PIK3CA mutations in 11/87 (13%) of bladder cancers (Lopez-Knowles et al 2006).…”

Section: Pik3ca Is Mutated In a Wide Variety Of Human Tumor Typesmentioning

confidence: 99%

Oncogenic Mutations of PIK3CA in Human Cancers

Samuels

Waldman

2010

Current Topics in Microbiology and Immunology

251

246

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The involvement of the PIK3CA gene product p110a, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), in human cancer has been suggested for over 15 years, and support for this proposal had been provided by both genetic and functional studies, including most recently the discovery of common activating missense mutations of PIK3CA in a wide variety of common human tumor types. This chapter will focus on the discovery of these mutations and describes their relevance to a wide range of common human tumor types. Of note, the identification and functional analysis of the PIK3CA gene are reviewed in other chapters in this book. However, a brief mention will be made here of its general properties as background to our focus on the discovery of its cancer-specific mutations.

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Section: Pik3ca Is Mutated In a Wide Variety Of Human Tumor Typesmentioning

confidence: 99%

Oncogenic Mutations of PIK3CA in Human Cancers

Samuels

Waldman

2010

Current Topics in Microbiology and Immunology

251

246

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“…Studies on small series of penile cancer show frequent overexpression of EGFR, but there is no data on other HER receptors in penile cancer [18], [19]. One study by Andersson et al [20] investigated the mutational status of PIK3CA and PTEN genes in PSCC but not protein expression. Therefore, we decided to investigate the role of this pathway in PSCC more fully, including all members of HER family, PTEN and Akt status and EGFR and PTEN gene copy number, using immunohistochemistry and fluorescent in situ hybridisation methods.…”

Section: Introductionmentioning

confidence: 99%

Alternative HER/PTEN/Akt Pathway Activation in HPV Positive and Negative Penile Carcinomas

Stankiewicz

Prowse

et al. 2011

PLoS ONE

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BackgroundThe pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog (PTEN) in HPV-positive and negative PSCC and its impact on Akt activation using immunohistochemistry and fluorescent in situ hybridisation (FISH).Methodology/Principal Findings148 PSCCs were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins. EGFR and PTEN gene status were also evaluated using FISH. HPV presence was assessed by PCR. pEGFR expression was detected significantly less frequently in HPV-positive than HPV-negative tumours (p = 0.0143). Conversely, HER3 expression was significantly more common in HPV-positive cases (p = 0.0128). HER4, pAkt, Akt and PTEN protein expression were not related to HPV. HER3 (p = 0.0054) and HER4 (p = 0.0002) receptors significantly correlated with cytoplasmic Akt1 immunostaining. All three proteins positively correlated with tumour grade (HER3, p = 0.0029; HER4, p = 0.0118; Akt1, p = 0.0001). pEGFR expression correlated with pAkt but not with tumour grade or stage. There was no EGFR gene amplification. HER2 was not detected. PTEN protein expression was reduced or absent in 62% of tumours but PTEN gene copy loss was present only in 4% of PSCCs.Conclusions/SignificanceEGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis. HPV-negative tumours tend to express significantly more pEGFR than HPV-positive cancers and this expression correlates with pAkt protein, indicating EGFR as an upstream regulator of Akt signalling in PSCC. Conversely, HER3 expression is significantly more common in HPV-positive cases and positively correlates with cytoplasmic Akt1 expression. HER4 and PTEN protein expression are not related to HPV infection. Our results suggest that PSCC patients could benefit from therapies developed to target HER receptors.

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“…25, 26 Dysregulation of these pathways have been associated with both penile cancer development and progression. 27 However, ours is the first study to analyze IGF1R expression in penile cancer.…”

Section: Discussionmentioning

confidence: 93%

Overexpression of Insulin-like Growth Factor-1 Receptor Is Associated With Penile Cancer Progression

Ball

Bezerra

Chaux

et al. 2016

Urology

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Objective To evaluate insulin-like growth factor-1 receptor (IGF1R) expression in penile cancer and its association with oncologic outcomes. Methods Tissue microarrays were constructed from 53 patients treated at our institution. Expression of IGF1R was evaluated using a Her2-like scoring system. Overexpression was defined as 1+ or greater membranous staining. Association of IGF1R expression with pathologic features was assessed with comparative statistics, and association with local recurrence, progression to nodal or distance metastases or death was assessed with Kaplan-Meier survival analysis and Cox proportional hazard regression models. Results Overall, IGF1R overexpression was seen in 33 (62%) cases. With a median follow-up of 27.8 months, IGF1R overexpression was associated with inferior progression-free survival (PFS) (p=0.003). In a multivariable model controlling for grade, T stage, PNI and lymphovascular invasion, IGF1R expression was independently associated with disease progression (HR 2.3, 95%CI 1.1–5.1, p = 0.03. Comparing patients without IGF1R over-expression to those with over-expression, 5 year PFS was 94.1% vs 45.8%. Conclusions IGF1R over-expression was associated with inferior PFS in penile cancer. Drugs that target IGF1R and downstream messengers may have a therapeutic benefit in patients that exhibit IGF1R over-expression.

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PIK3CA, HRAS and KRAS Gene Mutations in Human Penile Cancer

Abstract: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

Cited by 46 publications

References 17 publications

Oncogenic Mutations of PIK3CA in Human Cancers

Oncogenic Mutations of PIK3CA in Human Cancers

Alternative HER/PTEN/Akt Pathway Activation in HPV Positive and Negative Penile Carcinomas

Overexpression of Insulin-like Growth Factor-1 Receptor Is Associated With Penile Cancer Progression

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