Immunohistochemical assessment of cellular proliferation marker Ki67 in relation to prostate radiotherapy fractionation and prognosis in Trans-CHHiP.


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Anna Wilkins1
1Institute of Cancer Research, LONDON

Abstract

Background

External beam radiotherapy is delivered using a uniform fractionation schedule for localised prostate tumours, individualising fractionation according to tumour biology could improve outcomes. Additionally recurrence rates following radiotherapy vary considerably, better prognostic markers could allow modulation of treatment according to risk.  The Trans-CHHiP sample collection (CRUKA12518) comprises blocks from over 2000 prostate patients who participated in CHHiP, a randomised trial of 3 radiotherapy fractionation schedules (CRUK/06/016). This study aimed to determine if the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiotherapy fractionation.

Method

A matched case:control study design was used, patients with biochemical or clinical failure >2 years after radiotherapy (BCR) were matched to patients without recurrence using established prognostic factors (Gleason score, presenting PSA, tumour-stage) and fractionation schedule.  Immunohistochemical staining of diagnostic biopsy sections was carried out using the MIB1 Ki67 antibody. Two independent investigators scored Ki67 using the unweighted global method to derive a mean and maximum percentage of cells staining positive. Conditional logistic regression models were fitted to estimate the prognostic value of Ki67 on the risk of BCR. Biomarker x fractionation interaction terms were included to determine whether Ki67 was predictive of BCR by fractionation.

Results

Ki67 results were available for 173 cases matched to 173 controls. The median(IQR) for mean and maximum Ki67 were 6.6(3.9-9.8) and 11.0(7.0-15.0) respectively. Both scores were significant prognostic markers for BCR in models adjusted for established prognostic factors. Conditioning on the matching variables and age, the odds of BCR is estimated to increase by 9% per 1 point increase in mean Ki67 score (OR=1.09, 95%CI:1.04–1.15, p=0.001). 

Interaction terms between Ki67 and fractionation schedules were not statistically significant.

Conclusion

Ki67 did not predict BCR according to fractionation schedule in the CHHiP trial, however it was strongly prognostic of BCR risk independent of established prognostic factors.