Differential activation of ERK signaling in HPV-related oropharyngeal squamous cell carcinoma

• Verfasst von: Rong, Chao [VerfasserIn]
• Verfasst von: Flechtenmacher, Christa [VerfasserIn]
• Verfasst von: Dyckhoff, Gerhard [VerfasserIn]
• Verfasst von: Bulut, Cem [VerfasserIn]
• Verfasst von: Horn, Dominik [VerfasserIn]
• Verfasst von: Plinkert, Peter K. [VerfasserIn]
• Verfasst von: Heß, Jochen [VerfasserIn]
• Verfasst von: Affolter, Annette [VerfasserIn]
• Titel: Differential activation of ERK signaling in HPV-related oropharyngeal squamous cell carcinoma
• Verf.angabe: Chao Rong, Marie Muller, Christa Flechtenmacher, Dana Holzinger, Gerhard Dyckhoff, Olcay Cem Bulut, Dominik Horn, Peter Plinkert, Jochen Hess and Annette Affolter
• E-Jahr: 2019
• Jahr: 25 April 2019
• Umfang: 14 S.
• Fussnoten: Gesehen am 06.11.2019
• Titel Quelle: Enthalten in: Cancers
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2019
• Band/Heft Quelle: 11(2019,4) Artikel-Nr. 584, 14 Seiten
• ISSN Quelle: 2072-6694
• DOI: doi:10.3390/cancers11040584
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AKT
• Sach-SW: human papillomavirus
• Sach-SW: MAPK/ERK
• Sach-SW: oropharyngeal squamous cell carcinoma
• Sach-SW: prognostic biomarker
• Sach-SW: tissue microarray
• K10plus-PPN: 1681208881
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) forms a distinct tumor entity with better survival clinical outcome. Numerous underlying molecular mechanisms have been postulated for differences in treatment response, but the impact of MEK/ERK signaling, a main driver of carcinogenesis in various cancers including OPSCC and key player mediating therapy resistance remains elusive. In a retrospective experimental cohort study, primary tumor samples from OPSCC patients (n = 124) were available on tissue microarrays (TMAs) and expression levels of phosphorylated ERK1/2 (pERK1/2) were detected by immunohistochemical staining. Correlations of pERK1/2 expression patterns with clinicopathological features and clinical outcome were evaluated by statistical analysis. A low pERK1/2 expression was strongly associated with HPV-related OPSCC, while primary tumors with high pERK1/2 staining showed a distinctly worse survival outcome and were associated with higher cellular differentiation. Co-activation of both ERK1/2 and AKT was a common event and was associated with unfavorable prognosis in our cohort. However, the combinatorial analysis of pAKT (Ser473) and pERK1/2 did not strengthen the predictive power of pERK1/2, suggesting that pERK1/2 plays a more significant function in OPSCC. In summary, our data provide a compelling experimental and statistical evidence that low levels of tumor cell intrinsic ERK1/2 activation contribute at least in part to the favorable outcome of HPV-related OPSCC. On the other hand, presented findings indicate that non-HPV-related OPSCC with elevated ERK phosphorylation are at high risk for treatment failure and might benefit from targeted therapy of MEK/ERK signaling.