Abstract
Novel markers are needed to accurately predict the risk of malignant transformation in laryngeal premalignancies. We therefore investigated the clinical significance of cortactin (CTTN) and focal adhesion kinase (FAK) during laryngeal tumorigenesis and their potential utility as cancer risk markers. CTTN and FAK protein expression and gene amplification were assessed in 82 patients with laryngeal dysplasia and correlated with clinicopathologic parameters and laryngeal cancer risk. Increased CTTN and FAK expression was found respectively in 41 (50%) and 40 (49%) of 82 laryngeal dysplasias; protein expression was maintained or further augmented in the corresponding patient-matched invasive tumors subsequently developed. CTTN and FAK/PTK2 gene amplifications were respectively detected in 10 (12%) and 26 (32%) laryngeal dysplasias. Both CTTN and FAK protein expression increased with the grade of dysplasia; however, CTTN and FAK expression but not histology correlated significantly with increased laryngeal cancer risk (P = 0.009 and P = 0.002, respectively). Patients carrying strong CTTN- or FAK-expressing dysplastic lesions experienced a significantly higher cancer incidence (P = 0.006 and P = 0.001, respectively; log-rank test). Furthermore, FAK expression was an independent predictor of laryngeal cancer development (HR = 3.706, 95% CI: 1.735-7.916; P = 0.001) and the combination of FAK and CTTN showed superior predictive value (HR = 5.042, 95% CI: 2.255-11.274; P < 0.001). Taken together, our findings support the involvement of CTTN and FAK in malignant transformation and provide original evidence for their potential clinical utility as biomarkers for the risk of developing laryngeal cancer.
Highlights
Like other epithelial cancers, head and neck carcinogenesis seems to evolve through a multistep process that involves biomolecular changes caused by carcinogen exposure, ensuing premalignant lesions, and consequent invasive carcinoma [1,2,3]
This study is the first to investigate CTTN and focal adhesion kinase (FAK) protein expression and gene status in laryngeal tumorigenesis to ascertain their role in malignant transformation
Our findings show that CTTN and FAK are both frequently abnormally expressed in the early stages of laryngeal tumorigenesis and that patients carrying strong CTTN- or FAK-expressing dysplastic lesions exhibit a significantly higher cancer incidence than those with weak to moderate expression
Summary
Head and neck carcinogenesis seems to evolve through a multistep process that involves biomolecular changes caused by carcinogen exposure, ensuing premalignant lesions, and consequent invasive carcinoma [1,2,3]. The spectrum of histologic changes occurring in this process has been cumulatively designated squamous intraepithelial lesions (SIL), ranging from squa-. One of the most important issues of SILs is the risk of malignant transformation. In their evolution, some SILs are self-limiting and reversible, some persist, and some progress to squamous carcinoma despite careful follow-up and treatment. Lesions with dysplastic features are thought to be at a higher cancer risk, some cancers develop from lesions lacking dysplastic changes. Additional objective and reliable markers are needed to identify high-risk lesions to improve the prognostic evaluation of SILs beyond current clinical and histopathologic criteria [3]
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