PIK3CA copy number aberration and activation of the PI3K-AKT-mTOR pathway in varied disease states of penile cancer
BACKGROUND: Therapeutic targeting of the PI3K-AKT-mTOR pathway may benefit patients with advanced penile squamous cell carcinoma (PSCC).
OBJECTIVES: To determine the prevalence of PIK3CA copy number gain and correlate this with the activity status of PI3K-AKT-mTOR pathway in pre-malignant penile intraepithelial neoplasia (PeIN) and invasive PSCC.
MATERIALS AND METHODS: Archival tissue blocks were obtained from 58 PeIN and 244 primary PSCC patients treated at St George's Hospital. PIK3CA copy number status (CNS) was assessed by fluorescence in-situ hybridisation. High-risk HPV DNA was detected with INNO-LiPA assay. p16INK4A, p-AKT and p-mTOR protein expression were assessed using immunohistochemistry (IHC).
RESULTS: Increased prevalence of PIK3CA copy number gain was seen in PSCC in comparison to PeIN (84/199 (42%) vs. 10/58 (17%); p = 0.0009). Analysis of the p-AKT and p-mTOR revealed a tendency to a more common expression of cytoplasmic p-AKT (p = 0.1318), nuclear p-AKT (p<0.0001) and cytoplasmic mTOR (p = 0.0006) in PeIN than PSCC. A significant association between p-AKT cytoplasmic immunoexpression and PIK3CA CNS (p = 0.0404) was found in PeIN.
CONCLUSION: Overall, PIK3CA copy number gain correlated with activation of the PI3K-AKT-mTOR pathway in PeIN and activation of this pathway is primarily involved in early penile carcinogenesis. Based on these results therapeutic targeting of this pathway in advanced PSCC is unlikely to produce significant clinical benefit. Future studies will need to focus on alternative therapeutic targets.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
PloS one - 13(2018), 6 vom: 15., Seite e0198905 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Adimonye, Anthony [VerfasserIn] |
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| Links: |
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| Themen: |
Class I Phosphatidylinositol 3-Kinases |
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| Anmerkungen: |
Date Completed 31.12.2018 Date Revised 04.12.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0198905 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM285465589 |
|---|
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| 041 | |a eng | ||
| 100 | 1 | |a Adimonye, Anthony |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a PIK3CA copy number aberration and activation of the PI3K-AKT-mTOR pathway in varied disease states of penile cancer |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 31.12.2018 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Therapeutic targeting of the PI3K-AKT-mTOR pathway may benefit patients with advanced penile squamous cell carcinoma (PSCC) | ||
| 520 | |a OBJECTIVES: To determine the prevalence of PIK3CA copy number gain and correlate this with the activity status of PI3K-AKT-mTOR pathway in pre-malignant penile intraepithelial neoplasia (PeIN) and invasive PSCC | ||
| 520 | |a MATERIALS AND METHODS: Archival tissue blocks were obtained from 58 PeIN and 244 primary PSCC patients treated at St George's Hospital. PIK3CA copy number status (CNS) was assessed by fluorescence in-situ hybridisation. High-risk HPV DNA was detected with INNO-LiPA assay. p16INK4A, p-AKT and p-mTOR protein expression were assessed using immunohistochemistry (IHC) | ||
| 520 | |a RESULTS: Increased prevalence of PIK3CA copy number gain was seen in PSCC in comparison to PeIN (84/199 (42%) vs. 10/58 (17%); p = 0.0009). Analysis of the p-AKT and p-mTOR revealed a tendency to a more common expression of cytoplasmic p-AKT (p = 0.1318), nuclear p-AKT (p<0.0001) and cytoplasmic mTOR (p = 0.0006) in PeIN than PSCC. A significant association between p-AKT cytoplasmic immunoexpression and PIK3CA CNS (p = 0.0404) was found in PeIN | ||
| 520 | |a CONCLUSION: Overall, PIK3CA copy number gain correlated with activation of the PI3K-AKT-mTOR pathway in PeIN and activation of this pathway is primarily involved in early penile carcinogenesis. Based on these results therapeutic targeting of this pathway in advanced PSCC is unlikely to produce significant clinical benefit. Future studies will need to focus on alternative therapeutic targets | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Class I Phosphatidylinositol 3-Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.1.137 |2 NLM | |
| 650 | 7 | |a PIK3CA protein, human |2 NLM | |
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| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Stankiewicz, Elzbieta |e verfasserin |4 aut | |
| 700 | 1 | |a La-Touche, Susannah |e verfasserin |4 aut | |
| 700 | 1 | |a Kudahetti, Sakunthala |e verfasserin |4 aut | |
| 700 | 1 | |a Trevisan, Giorgia |e verfasserin |4 aut | |
| 700 | 1 | |a Tinwell, Brendan |e verfasserin |4 aut | |
| 700 | 1 | |a Corbishley, Cathy |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yong-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Watkin, Nick |e verfasserin |4 aut | |
| 700 | 1 | |a Berney, Daniel |e verfasserin |4 aut | |
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