Basal Ki67 expression measured by digital image analysis is optimal for prognostication in oral squamous cell carcinoma.
OBJECTIVE
The prognostic significance of Ki67 expression in cancers, including oral squamous cell carcinoma (OSCC), is unclear. This may be partly attributed to the lack of consensus surrounding the optimal approach for measuring tumour Ki67 expression. The aim of this study was to evaluate the association between different measures of Ki67 expression and disease-specific survival (DSS) in OSCC.


METHODS
Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded (FFPE) pre-treatment tumour tissue obtained from 121 OSCC patients diagnosed between 1998 and 2006. Ki67 expression was quantified using fluorescence immunohistochemistry (IHC) and AQUAnalysis® in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Intensity and percentage-based approaches for Ki67 scoring were tested for their association with survival.


RESULTS
Ki67 scores obtained from intensity and percentage-based approaches had similar associations with prognosis. We also found that high basal (lowest observed in triplicate cores) Ki67 expression was more strongly associated with improved 5-year disease-specific survival than hot-spot and average Ki67 measurements. The association of high basal Ki67 expression with improved prognosis was most pronounced in patients who received postoperative radiation. Cox proportional hazards analysis showed that the basal Ki67 expression is an independent prognostic marker in our OSCC cohort when adjusted for pathological T-stage, nodal status and treatment.


CONCLUSIONS
Our study provides a framework for reaching a consensus on the optimal approach for measuring Ki67 expression in cancers. Our results suggest that rigorous comparisons of measurement approaches should be applied in a tumour-type and treatment-specific manner to enhance the clinical application of Ki67 assessment.
Department of Oncology, University of Calgary, Calgary, Canada.
Alexander C
AC
Klimowicz
Pinaki
P
Bose
Steven C
SC
Nakoneshny
Michelle
M
Dean
Longlong
L
Huang
Shamir
S
Chandarana
Anthony M
AM
Magliocco
T
T
Wayne Matthews
Nigel T
NT
Brockton
Joseph C
JC
Dort
D000368:Aged; D000416:Alberta; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis / Q000379:methods*; D016896:Treatment Outcome
D019394:Ki-67 Antigen