Prognostic implication of stromal hyaluronic acid protein expression in resected oropharynx and oral cavity cancer

Abstract

Background: Hyaluronic acid (HA) is a well-characterized component of extracellular matrix (ECM), which plays a critical role in a variety of cellular processes and regulates cell adhesion, migration, and proliferation associated with prognosis of various tumor types. However, the clinical prognostic significance in resected head and neck squamous cell carcinoma (HNSCC) is not well identified. Methods: The resected tissues from oropharynx or oral cavity cancer patients undergoing surgery were made for tissue microarray (TMA) divided into stroma and cancer panels. Including HA protein expression, HA synthases (HAS) and hyaluronidases (HYAL1) was also assessed by immunohistochemistry. Results: A total of 160 resected oropharynx or oral cavity cancer tissues between 1994 and 2012 were analyzed in this study. Stromal HA expression, positive in 31 (19.4%) of patients, showed a trend favoring for HPV negative tumor. Other clinicopathological characteristics did not differ according to stromal HA protein expression. However, the HA expression in stroma were statistically associated with clinical outcomes. In the multivariate analysis for clinical outcomes, stromal HA expression was found to be an independent indicator for disease recurrence. (HR, 2.716; 95 % CI, 1.323 - 5.575, P = 0.007), and the combined analysis of tumoral and stromal expression of HA showed that patients with a cancer and stroma-positive HA expression showed a significantly worse outcome than those with other combinations (RFS, P = 0.023, OS, P = 0.082). In addition, when using stratification of HPV stastus, the stromal HA expression remained an independent indicator for disease recurrence and survival(HR, 2.712; 95% CI, 1.323 - 5.56; P = 0.006). Conclusions: The HA expression in stroma could be related with poor prognosis independently in surgically resected HNSCC. Thus, the finding suggested that HA in stroma may serve not only as a prognostic marker but also as a supposed target for HNSCC treatment.