Impact of PI3K-AKT-mTOR Signaling Pathway Up-regulation on Prognosis of Penile Squamous-Cell Carcinoma: Results From a Tissue Microarray Study and Review of the Literature
| Autor: | Jun-Min Zhou, Jasreman Dhillon, Peter A.S. Johnstone, Philippe E. Spiess, Anna R. Giuliano, Zhigang Yuan, Dominic H. Tang, Mounsif Azizi, Daniel Verduzco, Braydon Schaible, Charles C. Peyton, Juan Chipollini |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Oncology medicine.medical_specialty Urology 030232 urology & nephrology Article Cohort Studies Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Internal medicine Biomarkers Tumor medicine Carcinoma Humans PTEN Penile Neoplasms PI3K/AKT/mTOR pathway Aged Tissue microarray biology Proportional hazards model business.industry TOR Serine-Threonine Kinases Hazard ratio Middle Aged Prognosis medicine.disease Up-Regulation Gene Expression Regulation Neoplastic Survival Rate Tissue Array Analysis 030220 oncology & carcinogenesis Cohort Carcinoma Squamous Cell biology.protein Biomarker (medicine) Neoplasm Recurrence Local business Proto-Oncogene Proteins c-akt Follow-Up Studies Signal Transduction |
| Zdroj: | Clin Genitourin Cancer |
| ISSN: | 1558-7673 |
| Popis: | PI3K-AKT-mTOR signaling pathway dysregulation has been linked to the development of various malignancies, with only limited and conflicting reports in penile squamous-cell carcinoma (PSCC). Tissue microarrays of 57 cases of invasive PSCC were immunohistochemically stained for 3 proteins of the mTOR pathway: PTEN, AKT, and S6. Up-regulation of PI3K-AKT-mTOR and human papillomavirus coinfection in PSCC were associated with favorable disease. PURPOSE: To assess the prognostic value of PI3K-AKT-mTOR signaling pathway up-regulation in a contemporary cohort of penile squamous-cell carcinoma (PSCC) patients. PATIENTS AND METHODS: Tissue microarrays were constructed for 57 patients with invasive PSCC treated at our institution between 2000 and 2013. Immunohistochemical staining was performed for PTEN, AKT, and S6. Human papillomavirus (HPV) in-situ hybridization for high-risk subtypes was also performed. Biomarker expression was evaluated by a semiquantitative H score. Overall survival, disease-specific survival and recurrence-free survival stratified by biomarker expression (low vs. high) were estimated by the Kaplan-Meier method. Multivariable Cox regression models were used to determine predictors of mortality and recurrence. RESULTS: HPV in-situ hybridization was positive in 23 patients (40%). PTEN was down-regulated in 43 patients (75%), while phosphorylated-AKT (p-AKT) and phosphorylated-S6 (p-S6) were up-regulated in 27 (47%) and 12 patients (21%), respectively. In multivariable Cox regression models, patients with low expression of p-AKT had an increased risk of recurrence (hazard ratio [HR] = 3.95; 95% confidence interval [CI], 1.47–10.59; P = .02), while those with low expression of p-S6 had an increased risk of overall mortality (HR = 6.15; 95% CI, 1.55–24.36; P = .01). HPV status was an independent predictor of overall survival (HR = 6.99; 95% CI, 2.42–20.16; P < .001) and disease-specific survival (HR = 6.74; 95% CI, 2.02–22.48; P = .002). CONCLUSION: PI3K-AKTmTOR signaling pathway up-regulation and HPV coinfection in PSCC are associated with favorable disease. mTOR pathway biomarkers along with HPV status may represent novel prognosticators for risk stratification of PSCC patients and may help guide treatment decisions and follow-up strategies. These findings require further investigation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect