Abstract 4355: Prognostic significance of RUNX2 protein expression in carcinomas of the prostate (PAC), colon (CRC), and breast (BC)

Abstract

Abstract Background: RUNX2, a member of the RUNX family of transcription factors, regulates normal bone, cartilage and skeletal muscle morphogenesis. Aberrant RUNX2 expression has correlated with malignant cell migration, invasion and bone metastases. In the following study, we evaluated the prognostic significance of RUNX2 protein expression in a large cohort of tumors from each of three sites of origin - prostate, colon and breast. Design: Formalin-fixed paraffin-embedded tissue sections from 121 PAC, 104 CRC and 82 invasive BC [64 ductal (IDC); 18 lobular (ILC)] were immunostained by a manual method (DAKO LSAB+ System-HRP) using mouse monoclonal RUNX2 (Santa Cruz). Nuclear and/or cytoplasmic immunoreactivity was scored based on intensity and percentage of positive cells in both the tumor (T) and adjacent benign (B) epithelium in each case. Cases were assessed as tumor>benign (T>B), tumor = benign (T = B), tumor<benign (T<B) or negative (N). Results were correlated with clinicopathologic variables. Results: RUNX2 immunoreactivity was predominately nuclear in PAC, CRC and BC and noted as follows: in PACs: T>B 58%, T = B 31%, T<B 3% N 8%; and correlated with high [> = Gleason grade 7] vs low [< = Gleason grade 6] tumor grade (p = 0.001), advanced [stage III, IV] vs early [stage I, II] tumor stage (p = 0.039) and biochemical disease recurrence (p = 0.008). In CRCs, immunoreactivity was noted as: T>B 61%, T = B 22%, T<B 15% N 2%; and correlated with advanced [stage III, IV] vs early [stage I, II] tumor stage (p<0.0001); positive lymph node status (p = 0.001); high [grade 3 vs grade 2 vs grade 1] tumor grade (p = 0.012); and on Cox univariate analysis with shortened overall survival (p = 0.05). While in BCs: T>B 65% and T = B 35%; and correlated overall with early [stage I, II] vs advanced [stage III, IV] tumor stage (p = 0.05); ER positive status (p = 0.028); and on Cox univariate analysis, correlated with both lengthened recurrence free (p = 0.033) and overall (p = 0.042) survival; and showed a trend toward association with PR positive status (p = 0.075). Within the ER negative BC subgroup, RUNX2 immunoreactivity correlated with early tumor stage (p = 0.008) and PR positive status (p = 0.033). Conclusion: While RUNX2 protein expression correlates with adverse prognostic variables in prostate and colon cancers, RUNX2 immunoreactivity portends favorable prognosis in breast cancer. Further study of RUNX2 expression and its potential role as a therapeutic target particularly in PAC and CRC appear warranted. Citation Format: Bhaskar V.S. Kallakury, Albert Huho, Ann B. Boguniewicz, David M. Jones, Tipu Nazeer, Hwa Jeong Lee, Christine E. Sheehan, Jeffrey S. Ross. Prognostic significance of RUNX2 protein expression in carcinomas of the prostate (PAC), colon (CRC), and breast (BC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4355. doi:10.1158/1538-7445.AM2015-4355