Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review

Abstract

Some laryngeal epithelial precursor lesions progress to invasive carcinoma and others do not. Routine light microscopic classification has limited value in predicting the evolution of these lesions. This article reviews the experience to date with the use of molecular markers for the prognostic evaluation of laryngeal epithelial precursor lesions. We conducted a thorough review of the published literature to identify those studies using biomarkers to predict malignant progression of laryngeal epithelial precursor lesions. Of the 336 studies identified in this systematic search, 15 met the inclusion criteria and form the basis of this review. Limited studies suggest that certain biomarkers are potentially reliable predictors of malignant progression including various regulators of cell adhesion and invasion (e.g. FAK, cortactin, osteopontin, and CD44v6) and proliferation-associated markers such as TGF-βRII and Kv3.4. The predictive value of these markers, however, has yet to be confirmed in large-scale prospective studies. Although the cell cycle-related proteins are the most frequently studied markers, none have been consistently reliable across multiple studies. The absence of standardization in methodologies, test interpretation, and other parameters may contribute to study inconsistencies. Various biomarkers have proved to have potential prognostic value and could be clinically relevant. The utility and prognostic power of these biomarkers should be confirmed in large, well-designed, standardized prospective studies.

The Novel Role of SOX2 as an Early Predictor of Cancer Risk in Patients with Laryngeal Precancerous Lesions

“…This emphasizes the still limited value of histological grading to predict outcome, which is certainly affected by inter- and intra-observer variability [39]. Additional objective and reliable markers are therefore needed to improve patient stratification and to more accurately identify those carrying lesions at higher risk of progression who will require the most intense treatment and follow-up [40]. Our results clearly demonstrate that SOX2 protein analysis may provide valuable additional information beyond histological features.…”

Kv3.1 and Kv3.4, Are Involved in Cancer Cell Migration and Invasion

“…Therefore, according to the data, Kv3.1 and Kv3.4, which are specific targets of BDS-II, may be good biomarkers and therapeutic targets for cancer metastasis. In fact, Kv3.4 has already been suggested to be a strong biomarker candidate for predicting the malignant progression of laryngeal epithelial precursor lesions [ 36 ] or head and neck squamous cell carcinomas [ 37 ].…”

Evaluation of a new grading system for laryngeal squamous intraepithelial lesions—a proposed unified classification

“…[1][2][3][4][5][6] The aetiological, genetic, immunological and morphological parameters of the wide spectrum of epithelial changes, also called laryngeal squamous intraepithelial lesions (SILs), have been investigated for decades, in order to assign more reliable predictive values for malignant progression. [7][8][9][10][11][12][13][14][15][16] Despite extensive research in molecular genetics, reliable marker(s) with diagnostic and prognostic value are still lacking. Traditional light microscopic examination thus remains the mainstay of accurate diagnosis, in spite of the subjectivity in interpretation.…”

“…Laryngeal carcinogenesis is an incompletely understood, multistep process in which the progressive accumulation of genetic changes is followed by increasing architectural and cytological alterations of the laryngeal squamous epithelium . The aetiological, genetic, immunological and morphological parameters of the wide spectrum of epithelial changes, also called laryngeal squamous intraepithelial lesions (SILs), have been investigated for decades, in order to assign more reliable predictive values for malignant progression . Despite extensive research in molecular genetics, reliable marker(s) with diagnostic and prognostic value are still lacking.…”