OPN/CD44v6 overexpression in laryngeal dysplasia and correlation with clinical outcome

Abstract

Laryngeal dysplasia is a common clinical concern. Despite major advancements, a significant number of patients with this condition progress to invasive squamous cell carcinoma. Osteopontin (OPN) is a secreted glycoprotein, whose expression is markedly elevated in several types of cancers. We explored OPN as a candidate biomarker for laryngeal dysplasia. To this aim, we examined OPN expression in 82 cases of dysplasia and in hyperplastic and normal tissue samples. OPN expression was elevated in all severe dysplasia samples, but not hyperplastic samples, with respect to matched normal mucosa. OPN expression levels correlated positively with degree of dysplasia (P ¼ 0.0094) and negatively with disease-free survival (Po0.0001). OPN expression was paralleled by cell surface reactivity for CD44v6, an OPN functional receptor. CD44v6 expression correlated negatively with disease-free survival, as well (P ¼ 0.0007). Taken as a whole, our finding identify OPN and CD44v6 as predictive markers of recurrence or aggressiveness in laryngeal intraepithelial neoplasia, and overall, point out an important signalling complex in the evolution of laryngeal dysplasia.

CD44 Expression Is Predictive of Poor Prognosis in Pharyngolaryngeal Cancer: Systematic Review and Meta-Analysis

“…These reports demonstrated that CD44 was closely related with lymph node metastasis, which were well supported by our meta-analysis. CD44s,v3,v5,v6,and v9 have been reported to be expressed in the HNSCC of the head and neck (Piffko et al 1996;Ue et al 1998;Rodrigo et al 2003;Huang et al 2007;Staibano et al 2007). Studies have shown the distinct function of specific CD44 isoforms in cancer progression.…”

“…The features of the 19 eligible studies are listed in Table 1; 1 study was from each of the following countries: Spain (Esteban et al 2005),Turkey (Yuce et al 2011), Italy (Staibano et al 2007), Finland (Kokko et al 2011), and the USA (Janisiewicz et al 2012), two studies were from Japan (Kawano et al 2004;Uwa et al 2011), and 12 were from China (Song et al 1999;Wang et al 2000;Zhao et al 2003;Xu et al 2003;Wang et al 2004;Qiu et al 2006;Huang et al 2007;Lu et al 2008;Ma et al 2009;Gao 2009;Guo et al 2009;Lu et al 2011). Three studies focused on pharyngeal cancer, 14 focused on laryngeal cancer, and 2 studied both laryngeal and pharyngeal cancer.…”

“…Among the exons, ten exons are constitutively expressed to produce a 85-to 90-Kd isoform named as CD44 standard form (CD44s), whereas other isoforms called CD44 variants (CD44v), are generated by alternatively spliced transcripts (Zoller 2011). Up to date, CD44v6 was the most reported isoform in pharyngolaryngeal cancer (Song et al 1999;Wang et al 2000;Kawano et al 2004;Andratschke et al 2005;Staibano et al 2007;Huang et al 2007;Lu et al 2008;Guo et al 2009;Gao 2009). …”

Novel Markers for Diagnosis and Prognosis of Oral Intraepithelial Neoplasia

“…In cell culture, blockade of these CD44 isoforms with isoformspecific antibodies inhibited cellular proliferation, with the greatest inhibition seen with blockade of CD44 v6. Finally, increased expression of CD44 v6 and v10 was associated with shortened disease-free survival (Staibano et al 2007). These studies suggest that alteration in CSC phenotype through variation in CD44 isoform expression may alter the interaction of CSCs with the surrounding microenvironment.…”

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

“…CD44+CD24 CSCs play a critical role in tumor progression and metastasis [19] . Some of HNSCC with CD44s (standard form) and CD44 v6 (alternative splice variant) ex pressions are associated with a poorer diseasefree survival, in laryngeal cancers particularly [20] . Also, high levels of nuclear BMI1 were found in CD44+CD24 cells of the tumor population.…”