The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma

• Published in: British journal of cancer Vol. 109; no. 7; pp. 1859 - 1866
• Main Authors: KLIMOWICZ, A. C, BOSE, P, PETRILLO, S. K, MAGLIOCCO, A. M, DORT, J. C, BROCKTON, N. T
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.10.2013
• Subjects: Antigens, Neoplasm - metabolism; Apoptosis; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cancer therapies; Carbonic Anhydrase IX; Carbonic Anhydrases - metabolism; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Cell Hypoxia; Drug Resistance, Neoplasm; Female; Humans; Hypoxia; Ki-67 Antigen - metabolism; Male; Medical prognosis; Medical research; Medical sciences; Middle Aged; Molecular Diagnostics; Mouth Neoplasms - metabolism; Mouth Neoplasms - mortality; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Otorhinolaryngology. Stomatology; Prognosis; Survival; Treatment Outcome; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Canada; Calgary Alberta Canada; Alberta Canada; United States > US; Oxygen; AQUA; Prognosis; Oral cancer; Enzyme; Stomatology; Biological marker; Lyases; Malignant tumor; Oral squamous cell carcinoma; CAIX; Cancerology; Ki67 antigen; ENT disease; Head and neck cancer; Head and neck squamous cell carcinoma; Hypoxia; Oral cavity disease; Carbonate dehydratase; Ki67; Carbon-oxygen lyases; Cancer; Hydro-lyases
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.533

Tumour hypoxia is associated with impaired apoptosis, resistance to therapy and poor prognosis. We previously reported that high stromal expression of the endogenous marker of hypoxia, carbonic anhydrase IX (CAIX), is associated with significantly reduced survival in oral squamous cell carcinoma (OSCC). In addition to hypoxia, CAIX expression is regulated by proliferation-associated signalling. We hypothesised that incorporating Ki67, a proliferation marker, into our existing CAIX-based stratification of OSCC would identify patients with the least favourable prognosis. Surgically resected tumours from 60 OSCC patients were analysed for CAIX, Ki67 and BAX expression using fluorescence immunohistochemistry and automated quantitative analysis (AQUA). In patients expressing high stromal CAIX (sCAIX), stratification by tumour Ki67 expression revealed significantly distinct survival outcomes (P=0.005). In our OSCC cohort, below-median Ki67 and top-quartile sCAIX expression (Ki67(lo)sCAIX(hi)) were associated with significantly worse disease-specific survival in univariate (HR 7.2 (2.5-20.4), P=0.001) and multivariate (HR 4.2 (1.4-12.8), P=0.011) analyses. Hypoxia is associated with decreased BAX expression; the Ki67(lo)sCAIX(hi) group was more strongly associated with low BAX expression than high sCAIX alone. These data suggest that combined analysis of tumour Ki67 and sCAIX expression may provide a more clinically relevant assessment of tumour hypoxia in OSCC.