title: High stromal carbonic anhydrase IX expression is associated with nodal metastasis and decreased survival in patients with surgically-treated oral cavity squamous cell carcinoma.
abstract: Every year, approximately 25,000 patients are diagnosed with oral cavity squamous cell carcinoma (OCSCC) in the USA. The 5-year survival rate for OCSCC is approximately 40%. Intratumoral hypoxia confers poor prognosis and treatment failure but direct tumor oxygen measurement is challenging. Carbonic anhydrase IX (CAIX) is a marker of tissue hypoxia and we have recently shown that stromal CAIX is associated with reduced survival in patients with HPV-negative head and neck cancer. We examined the importance of this observation in OCSCC patients. We identified patients diagnosed and treated with OCSCC in Calgary (Alberta, Canada) between 1998 and 2005. Clinical and pathologic data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of archived tumor tissue. Stromal CAIX expression was assessed by quantitative immunohistochemistry (AQUA-HistoRx). The primary endpoint was disease-specific survival. We identified 102 patients with OCSCC; 87 patients had surgery as their primary treatment and adequate tumor tissue for TMA construction was available for all patients. CAIX expression was evaluable for 61 patients. High (top quartile) stromal CAIX expression was associated with significantly reduced 5-year disease-specific survival compared to low stromal CAIX expression (p<0.006). This study confirms our previously reported association between high stromal CAIX expression and significantly reduced overall survival in an independent, predominantly p16-negative, cohort of surgically treated OCSCC. Assessment of stromal CAIX expression could identify patients with the least favorable prognosis and inform therapeutic strategies in OCSCC.
authors.affiliation: Division of Preventive Oncology, Department of Oncology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Nigel T
authors.initials: NT
authors.lastname: Brockton
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Klimowicz
authors.forename: Pinaki
authors.initials: P
authors.lastname: Bose
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Petrillo
authors.forename: Mie
authors.initials: M
authors.lastname: Konno
authors.forename: Luke
authors.initials: L
authors.lastname: Rudmik
authors.forename: Michelle
authors.initials: M
authors.lastname: Dean
authors.forename: Steven C
authors.initials: SC
authors.lastname: Nakoneshny
authors.forename: T Wayne
authors.initials: TW
authors.lastname: Matthews
authors.forename: Shamir
authors.initials: S
authors.lastname: Chandarana
authors.forename: Harold Y
authors.initials: HY
authors.lastname: Lau
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Dort
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases