%0 Journal Article
%T Quantifying the Ki-67 Heterogeneity Profile in Prostate Cancer
%A Shane Mesko
%A Patrick Kupelian
%A D. Jeffrey Demanes
%A Jaoti Huang
%A Pin-Chieh Wang
%A Mitchell Kamrava
%J Prostate Cancer
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/717080
%X Background: Ki-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied. Methods: Using an MRI/US fusion device, biopsy cores were obtained systematically and by targeting when indicated by MRI. Prostate cores containing cancer from 77 consecutive men were analyzed. The highest Ki-67 was used to determine interprostatic variation. Ki-67 range (highest minus lowest) was used to determine intraprostatic and intralesion variation. Apparent diffusion coefficient (ADC) values were evaluated in relation to Ki-67. Results: Interprostatic Ki-67 mean ¡À standard deviation (SD) values for NCCN low (L), intermediate (I), and high (H) risk patients were 5.1 ¡À 3.8%, 7.4 ¡À 6.8%, and 12.0 ¡À 12.4% (ANOVA ). Intraprostatic mean ¡À SD Ki-67 ranges in L, I, and H risk patients were 2.6 ¡À 3.6%, 5.3 ¡À 6.8%, and 10.9 ¡À 12.3% (ANOVA ). Intralesion mean ¡À SD Ki-67 ranges in L, I, and H risk patients were 1.1 ¡À 0.9%, 5.2 ¡À 7.9%, and 8.1 ¡À 10.8% (ANOVA ). ADC values at Ki-67 > and <7.1% were 860 ¡À 203 and 1036 ¡À 217, respectively ( ). Conclusions: High risk patients have significantly higher inter- and intraprostatic Ki-67 heterogeneity. This needs to be considered when utilizing Ki-67 clinically. 1. Introduction Progress in multiparametric MRI imaging has improved our ability to visualize specific target lesions within the prostate. Ultrasound/MRI fusion devices allow for targeted biopsies of these specific MRI defined lesions. These advances create an opportunity to evaluate biomarkers from specific target lesions for integration into radiation treatment stratification. The Ki-67 protein functions as a nuclear antigen that is only expressed in proliferating cells. It is a marker of the growth fraction in malignant tissue [1¨C3]. It is determined via immunohistochemistry and expressed as a percentage of cells showing activity in a given tissue sample (e.g., Ki-67 of 10% equates to 10% of the cells expressing the antigen). It is a promising biomarker in prostate cancer with independent predictive/prognostic value following radiotherapy [4¨C6]. A range of percentage cut points has correlated with outcomes but has not been prospectively validated [7¨C11]. One limitation to integrating biomarkers into clinical practice is being able to account for tumor heterogeneity. Ki-67 heterogeneity has been acknowledged in liver, breast, and several other cancers but has not been well studied in prostate cancer [12¨C14]. Previous studies have used the highest Ki-67 level found on routine systematic prostate biopsy
%U http://www.hindawi.com/journals/pc/2013/717080/