TY - JOUR
T1 - Immunohistochemical expression of cortactin and focal adhesion kinase predicts recurrence risk and laryngeal cancer risk beyond histologic grading
AU - Villaronga, M. Ángeles
AU - Hermida-Prado, Francisco
AU - Granda-Díaz, Rocío
AU - Menéndez, Sofía T.
AU - Álvarez-Teijeiro, Saúl
AU - Quer, Miquel
AU - Vilaseca, Isabel
AU - Allonca, Eva
AU - Garzón-Arango, Marta
AU - Sanz-Moreno, Victoria
AU - Astudillo, Aurora
AU - Rodrigo, Juan P.
AU - García-Pedrero, Juana M.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Background: Cortactin (CTTN) and the focal adhesion kinase (FAK) are two major candidate genes to, respectively, drive 11q13-and 8q24-associated aggressive behavior in various cancers. Recent evidence uncovered their clinical relevance in early stages of tumor-igenesis as promising biomarkers for cancer risk assessment. Methods: Using a multicenter validation study, CTTN and FAK expression was evaluated by immunohistochemistry (IHC) in a cohort of 109 patients with laryngeal precancerous lesions, and correlated with clinicopathologic parameters and laryngeal cancer risk. The pathophysiologic role of CTTN and FAK was further investigated using functional studies in cellular models. Results: Positive CTTN and FAK expression (scores 2 and 3) was detected in 49 (41%) and 35 (32%) laryngeal dysplasias, respectively. Univariate Cox analysis showed that CTTN and FAK expression but not histologic grading was significantly associated with both recurrence risk and laryngeal cancer risk. Patients carrying strong CTTN- or FAK-expressing lesions (score 3) experienced the highest laryngeal cancer incidence (log-rank P < 0.001). In multivariate stepwise analysis, FAK expression [HR = 13.91; 95% CI, 4.82-40.15; P < 0.001] and alcohol consumption (HR = 2.22; 95% confidence interval, 1.17-4.20; P = 0.014) were significant independent predictors of laryngeal cancer development. Targeting FAK by either RNAi or pharmacologic inhibitors effectively blocked cell growth, colony formation, and invasion into 3D collagen matrices. Conclusions: CTTN and FAK emerge as powerful predictors of laryngeal cancer risk and recurrence risk beyond histologic grading. Impact: Our work supports the applicability of IHC CTTN and FAK as complementary markers for risk stratification in patients with laryngeal precancerous lesions.
AB - Background: Cortactin (CTTN) and the focal adhesion kinase (FAK) are two major candidate genes to, respectively, drive 11q13-and 8q24-associated aggressive behavior in various cancers. Recent evidence uncovered their clinical relevance in early stages of tumor-igenesis as promising biomarkers for cancer risk assessment. Methods: Using a multicenter validation study, CTTN and FAK expression was evaluated by immunohistochemistry (IHC) in a cohort of 109 patients with laryngeal precancerous lesions, and correlated with clinicopathologic parameters and laryngeal cancer risk. The pathophysiologic role of CTTN and FAK was further investigated using functional studies in cellular models. Results: Positive CTTN and FAK expression (scores 2 and 3) was detected in 49 (41%) and 35 (32%) laryngeal dysplasias, respectively. Univariate Cox analysis showed that CTTN and FAK expression but not histologic grading was significantly associated with both recurrence risk and laryngeal cancer risk. Patients carrying strong CTTN- or FAK-expressing lesions (score 3) experienced the highest laryngeal cancer incidence (log-rank P < 0.001). In multivariate stepwise analysis, FAK expression [HR = 13.91; 95% CI, 4.82-40.15; P < 0.001] and alcohol consumption (HR = 2.22; 95% confidence interval, 1.17-4.20; P = 0.014) were significant independent predictors of laryngeal cancer development. Targeting FAK by either RNAi or pharmacologic inhibitors effectively blocked cell growth, colony formation, and invasion into 3D collagen matrices. Conclusions: CTTN and FAK emerge as powerful predictors of laryngeal cancer risk and recurrence risk beyond histologic grading. Impact: Our work supports the applicability of IHC CTTN and FAK as complementary markers for risk stratification in patients with laryngeal precancerous lesions.
UR - http://www.scopus.com/inward/record.url?scp=85049611461&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-17-1082
DO - 10.1158/1055-9965.EPI-17-1082
M3 - Article
AN - SCOPUS:85049611461
SN - 1055-9965
VL - 27
SP - 805
EP - 813
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -
