Prognostic implications of stromal hyaluronic acid protein expression in resected oropharyngeal and oral cavity cancers
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Background/Aims: Hyaluronic acid (HA) regulates cell adhesion, migration and proliferation in various cancers. The clinical implications of HA in resected head and neck squamous cell carcinoma have not been elucidated. We investigated the clinical significance and prognostic value of the expression of tumoral and stromal HA and its related proteins in oropharyngeal and oral cavity cancer. Methods: Resected tissues from oropharyngeal or oral cavity cancer patients undergoing surgery were analysed in tissue microarrays divided into stroma and cancer panels. The expression levels of HA, HA synthases and hyaluronidases were also assessed by immunohistochemistry. Results: A total of 160 resected oropharyngeal or oral cavity cancer tissues were analysed. Stromal HA expression was observed more frequently in human papilloma virus (HPV)-negative tumors, but other clinicopathological characteristics did not differ. In patients with HPV-negative oral cavity cancers, high stromal HA expression was associated with significantly shorter recurrence-free survival and overall survival compared with low stromal HA expression. The expression of HA in both tumors and stroma was significantly correlated with poorer outcomes than other combinations in patients with HPV-negative oral cavity cancers. However, these prognostic roles of HA were not observed in patients with HPV-negative oropharyngeal cancers. In the HPV-stratified multivariate analysis, high stromal HA expression remained an independent indicator of poor prognosis in terms of recurrence-free survival. Conclusions: High stromal HA and expression of HA in both tumors and stroma were correlated with poor prognosis in HPV-negative oral cavity cancer, but not in HPV-negative oropharyngeal cancers.
Abstract
Background/Aims: Hyaluronic acid (HA) regulates cell adhesion, migration and proliferation in various cancers. The clinical implications of HA in resected head and neck squamous cell carcinoma have not been elucidated. We investigated the clinical significance and prognostic value of the expression of tumoral and stromal HA and its related proteins in oropharyngeal and oral cavity cancer. Methods: Resected tissues from oropharyngeal or oral cavity cancer patients undergoing surgery were analysed in tissue microarrays divided into stroma and cancer panels. The expression levels of HA, HA synthases and hyaluronidases were also assessed by immunohistochemistry. Results: A total of 160 resected oropharyngeal or oral cavity cancer tissues were analysed. Stromal HA expression was observed more frequently in human papilloma virus (HPV)-negative tumors, but other clinicopathological characteristics did not differ. In patients with HPV-negative oral cavity cancers, high stromal HA expression was associated with significantly shorter recurrence-free survival and overall survival compared with low stromal HA expression. The expression of HA in both tumors and stroma was significantly correlated with poorer outcomes than other combinations in patients with HPV-negative oral cavity cancers. However, these prognostic roles of HA were not observed in patients with HPV-negative oropharyngeal cancers. In the HPV-stratified multivariate analysis, high stromal HA expression remained an independent indicator of poor prognosis in terms of recurrence-free survival. Conclusions: High stromal HA and expression of HA in both tumors and stroma were correlated with poor prognosis in HPV-negative oral cavity cancer, but not in HPV-negative oropharyngeal cancers.
참고문헌 (30)
- Warnakulasuriya S, "Global epidemiology of oral and oropharyngeal cancer", Oral Oncol, 45, pp.309~316 (2009)
- Markovic A, "Current role of EGF receptor monoclonal antibodies and tyrosine kinase inhibitors in the management of head and neck squamous cell carcinoma", Expert Rev Anticancer Ther, 12, pp.1149~1159 (2012)
- Carinci F, "CD44 as prognostic factor in oral and oropharyngeal squamous cell carcinoma", J Craniofac Surg, 13, pp.85~89 (2002)
- McDonald JA, "Hyaluronan : genetic insights into the complex biology of a simple polysaccharide", Glycoconj J, 19, pp.331~339 (2002)
- Itano N, "Mammalian hyaluronan synthases", IUBMB Life, 54, pp.195~199 (2002)
- Stern R, "Hyaluronan catabolism : a new metabolic pathway", Eur J Cell Biol, 83, pp.317~325 (2004)
- Wang C, "Hyaluronan distribution in the normal epithelium of esophagus, stomach, and colon and their cancers", Am J Pathol, 148, pp.1861~1869 (1996)
- Ropponen K, "Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer", Cancer Res, 58, pp.342~347 (1998)
- Setala LP, "Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate", Br J Cancer, 79, pp.1133~1138 (1999)
- Auvinen P, "Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival", Am J Pathol, 156, pp.529~536 (2000)
- Byers LA, "An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance", Clin Cancer Res, 19, pp.279~290 (2013)
- Lassen P, "Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer", Radiother Oncol, 113, pp.310~316 (2014)
- Li L, "Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts : importance of hyaluronan for the mitogenic response of PDGF-BB", Biochem J, 404, pp.327~336 (2007)
- Toole BP, "Hyaluronan : from extracellular glue to pericellular cue", Nat Rev Cancer, 4, pp.528~539 (2004)
- Lokeshwar VB, "Stromal and epithelial expression of tumor markers hyaluronic acid and HYAL1 hyaluronidase in prostate cancer", J Biol Chem, 276, pp.11922~11932 (2001)
- Kosunen A, "Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma", Oral Oncol, 40, pp.257~263 (2004)
- Hirvikoski P, "Irregular expression of hyaluronan and its CD44 receptor is associated with metastatic phenotype in laryngeal squamous cell carcinoma", Virchows Arch, 434, pp.37~44 (1999)
- Kramer MW, "Association of hyaluronic acid family members(HAS1, HAS2, and HYAL-1)with bladder cancer diagnosis and prognosis", Cancer, 117, pp.1197~1209 (2011)
- Tan JX, "Upregulation of HYAL1expression in breast cancer promoted tumor cell proliferation, migration, invasion and angiogenesis", PLoS One, 6, pp.e22836~ (2011)
- McAtee CO, "Emerging roles for hyaluronidase in cancer metastasis and therapy", Adv Cancer Res, 123, pp.1~34 (2014)
- Okuda H, "Hyaluronan synthase HAS2 promotes tumor progression in bone by stimulating the interaction of breast cancer stem-like cells with macrophages and stromal cells", Cancer Res, 72, pp.537~547 (2012)
- Lien HC, "Differential expression of hyaluronan synthase 2 in breast carcinoma and its biological significance", Histopathology, 65, pp.328~339 (2014)
- Zhang Z, "Hyaluronan synthase 2expressed by cancer-associated fibroblasts promotes oral cancer invasion", J Exp Clin Cancer Res, 35, pp.181~ (2016)
- Kang H, "Emerging biomarkers in head and neck cancer in the era of genomics", Nat Rev Clin Oncol, 12, pp.11~26 (2015)
- Cancer Genome Atlas Network, "Comprehensive genomic characterization of head and neck squamous cell carcinomas", Nature, 517, pp.576~582 (2015)
- Chung CH, "Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression", Cancer Cell, 5, pp.489~500 (2004)
- Provenzano PP, "Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma", Cancer Cell, 21, pp.418~429 (2012)
- Thompson CB, "Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models", Mol Cancer Ther, 9, pp.3052~3064 (2010)
- Sato N, "Targeting hyaluronan for the treatment of pancreatic ductal adenocarcinoma", Acta Pharm Sin B, 6, pp.101~105 (2016)
- Hingorani SR, "HALO 202 : randomized phase II study of PEGPH20 plus nab-paclitaxel", gemcitabine versus nab-paclitaxel, J Clin Oncol, pp.2018, 36[DOI]