Insulin-like growth factor 1 receptor (IGF1R) expression and survival in operable squamous-cell laryngeal cancer.
| Title | Insulin-like growth factor 1 receptor (IGF1R) expression and survival in operable squamous-cell laryngeal cancer. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Mountzios, G., Kostopoulos I., Kotoula V., Sfakianaki I., Fountzilas E., Markou K., Karasmanis I., Leva S., Angouridakis N., Vlachtsis K., Nikolaou A., Konstantinidis I., & Fountzilas G. |
| Journal | PLoS One |
| Volume | 8 |
| Issue | 1 |
| Pagination | e54048 |
| Date Published | 2013 |
| ISSN | 1932-6203 |
| Keywords | Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell, Female, Gene Expression, Humans, Insulin-Like Growth Factor Binding Protein 3, Laryngeal Neoplasms, Male, MAP Kinase Kinase 1, Middle Aged, Mitogen-Activated Protein Kinase 9, Neoplasm Staging, Phosphatidylinositol 3-Kinases, Protein Isoforms, Receptor, IGF Type 1, Receptor, IGF Type 2, Suppressor of Cytokine Signaling Proteins, Survival Analysis, Tumor Markers, Biological |
| Abstract | INTRODUCTION: Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression.PATIENTS AND METHODS: We identified all patients with localized TNM stage I-III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS).RESULTS: Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504).CONCLUSION: IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted. |
| DOI | 10.1371/journal.pone.0054048 |
| Alternate Journal | PLoS ONE |
| PubMed ID | 23365645 |
| PubMed Central ID | PMC3554755 |
