Impact of tumoral carbonic anhydrase IX and Ki‑67 expression on survival in oral squamous cell carcinoma patients

Brockton,Nigel  T.; Lohavanichbutr,Pawadee; Enwere,Emeka K.; Upton,Melissa  P.; Kornaga,Elizabeth  N.; Nakoneshny,Steven  C.; Bose,Pinaki; Chen,Chu; Dort,Joseph  C.

doi:10.3892/ol.2017.6829

Impact of tumoral carbonic anhydrase IX and Ki‑67 expression on survival in oral squamous cell carcinoma patients

Authors:
- Nigel T. Brockton
- Pawadee Lohavanichbutr
- Emeka K. Enwere
- Melissa P. Upton
- Elizabeth N. Kornaga
- Steven C. Nakoneshny
- Pinaki Bose
- Chu Chen
- Joseph C. Dort
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Affiliations: Department of Cancer Epidemiology and Prevention Research, Cancer Control Alberta, Alberta Health Services, Calgary, AB T2S 3C3, Canada, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109‑1024, USA, Functional Tissue Imaging Unit, Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada, Department of Pathology, University of Washington, Seattle, WA 98195, USA, Ohlson Research Initiative, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada, Division of Otolaryngology‑Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, AB T2N 1N4, Canada
Published online on: August 25, 2017 https://doi.org/10.3892/ol.2017.6829
Pages: 5434-5442
Copyright: © Brockton et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oral squamous cell carcinoma (OSCC) is the most commonly diagnosed type of head and neck cancer, accounting for ~300,000 new cases worldwide annually. Carbonic anhydrase IX (CAIX) and Ki‑67 have been associated with reduced disease‑specific survival (DSS) in patients with OSCC. We previously proposed a combined CAIX and Ki‑67 signature of ‘functional hypoxia’ and sought to replicate this association in a larger independent cohort of patients with OSCC at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle. The study population included patients with incident primary OSCC treated at the University of Washington Medical Center and the Harborview Medical Center in Seattle between December 2003 and February 2012. Archived tumor blocks were obtained with tissue samples from 189 patients, and triplicate 0.6 mm cores were assembled into tissue microarrays (TMAs). Fluorescence immunohistochemistry and AQUAnalysis® were used to quantify the expression of tumoral CAIX (tCAIX) and stromal CAIX (sCAIX) and tumoral Ki‑67 for each TMA core. Hazard ratios for DSS were calculated using Cox proportional hazards analysis. High tCAIX and sCAIX expression levels were associated with reduced DSS (aHR=1.003, 95% CI:1.00‑1.01 and aHR=1.010, 95% CI:1.001‑1.019, per AQUA score unit, respectively). Ki‑67 expression was not associated with survival (aHR=1.01, 95% CI:0.99‑1.02) in the FHCRC cohort. DSS for patients with high sCAIX and low Ki‑67 did not differ from that of other patient groups. Elevated tCAIX was associated with reduced DSS as a continuous and as a dichotomized (75%) variable. sCAIX was associated with DSS as a continuous variable but not when dichotomized (75%). However, the previously proposed ‘functional hypoxia’ signature was not replicated in the current FHCRC study. The failure to replicate our prior observation of poorer survival in patients with combined high sCAIX and low tumoral Ki‑67 was likely due to the absence of an association between tumoral Ki‑67 and DSS in this cohort. However, the association between DSS and tCAIX and sCAIX supports a role for CAIX in OSCC clinical outcomes.

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