Phosphorylated mammalian target of rapamycin is associated with an adverse outcome in oral squamous cell carcinoma

Monteiro, Luís Silva; Delgado, L.; Ricardo, Sara; Garcez, Fernanda Rodrigues; Amaral, Barbas do; Warnakulasuriya, Saman; Lopes, Carlos

doi:10.1016/j.oooo.2013.01.022

Cited by 31 publications

(45 citation statements)

References 28 publications

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“…Rapamycin also suppresses angiogenesis by decreasing the production of vascular endothelial growth factor [29]. In accordance with our results, a recent study has shown that adverse outcomes are associated with high expression of mTOR in a subset of 72 oral SCCs [30]. Indeed, mTOR inhibitors have shown promising efficacy rates in patients with renal cell and gastric carcinomas [31,32].…”

Section: Discussionsupporting

confidence: 90%

Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis

et al. 2017

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Background: The development of oral cavity cancer is related to the accumulation of genetic alterations. The activation of AKT is associated with the proliferation and progression of many malignancies. It is thought that MAP kinases, together with the PI3K/AKT/mTOR signaling pathway, promote uncoordinated proliferation via inhibition of PTEN, thus increasing cell survival and mediating cancer progression. However, there are few studies regarding the expression of these proteins in oral squamous cell carcinoma (SCC).

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Section: Discussionsupporting

confidence: 90%

Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis

et al. 2017

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“…In a study by Monteiro et al. , p‐mTOR is observed in 46 (63.9%) oral squamous cell carcinoma (OSCC) cases, and an adverse independent prognostic value for high p‐mTOR expression occurs ( P = 0.043). Tumors with high p‐mTOR expression have lower OS.…”

Section: Resultsmentioning

confidence: 99%

mTOR pathway protein immunoexpression as a prognostic factor for survival in head and neck cancer patients: a systematic review and meta‐analysis

Marques

Elias

Porporatti

et al. 2015

J Oral Pathology Medicine

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“…For example, in a previous, independent analysis of 41 patients treated at MD Anderson Cancer Center, loss of PTEN expression in tongue cancer cells was associated with shorter overall survival and event-free survival. 11 Despite these various observations, a definitive prognostic role of PI3-kinase pathway activation in oral cavity squamous cell carcinomas is yet to be established. 12 Overexpression of p-Akt has been shown to be associated with shorter disease-free survival independently of classification and nodal status in a cohort of 52 patients with tongue cancer 10 and shorter overall survival in 2 cohorts of 84 9 and 191 8 patients with oral squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11][12] We therefore designed this study to investigate the hypothesis that PI3-kinase pathway dysregulation in head and neck cancer cells and/or tumor infiltrating immune cells would influence long-term outcomes of patients with oral tongue squamous cell carcinomas treated with surgical resection. [7][8][9][10][11][12] We therefore designed this study to investigate the hypothesis that PI3-kinase pathway dysregulation in head and neck cancer cells and/or tumor infiltrating immune cells would influence long-term outcomes of patients with oral tongue squamous cell carcinomas treated with surgical resection.…”

Section: Introductionmentioning

confidence: 99%

PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells

et al. 2018

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Background This study investigated the hypothesis that phosphoinositide 3‐kinase (PI3‐kinase) pathway dysregulation in either head and neck cancer cells and/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC). Methods We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3‐kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p‐Akt, mammalian target of rapamycin (mTOR), phosphorylated‐mammalian target of rapamycin (p‐mTOR), survivin, and Ki‐67). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes. Results Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence‐free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 0.23‐0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15‐0.76, P = .01) on univariate and multicovariate models. Conclusions We identified a novel, negative prognostic role of PI3‐kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI‐3 kinase inhibitors for this disease.

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Phosphorylated mammalian target of rapamycin is associated with an adverse outcome in oral squamous cell carcinoma

Cited by 31 publications

References 28 publications

Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis

Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis

mTOR pathway protein immunoexpression as a prognostic factor for survival in head and neck cancer patients: a systematic review and meta‐analysis

PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells

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