Abstract 4923: Expression of class III beta-tubulin (TUBB3) in 3580 colorectal cancers (CRCs) and correlation with clinico-pathological and molecular features
Authors: Joanne Xiu, Sandeep Reddy, Wafik S. El-Deiry
Journal: Cancer Research (2016)

Abstract Class III beta-tubulin plays a crucial role in intracellular transport, meiosis and mitosis. High expression of TUBB3 has been shown to associate with poor prognosis and taxane resistance in various cancer types. CRC is known to be generally resistant to taxane therapy. We investigated expression of TUBB3 in 3580 CRCs and made correlations with clinicopathological and molecular parameters. 3580 CRC samples were evaluated by tumor profiling (Caris Life Sciences, Phoenix, AZ). Tests included Sanger or next generation sequencing (NGS), protein expression by immunohistochemistry (IHC) and gene amplification by in situ hybridization (ISH). TUBB3 expression was evaluated by immunohistochemistry (Ab: POLY, Covance) and expression higher than 2+, 30% was scored as positive. TUBB3 positive expression was observed in 37% (1320/3580) of the complete CRC cohort, specifically 27% in mucinous histology (164/617) and 17% in signet ring histology (29/171). While the expression was not associated with average patient age (59 years old) or gender (53% vs. 50% male), TUBB3 was more frequently expressed in tumors that originated from the left colon (370/1016 or 36%) than from the right colon (235/790 or 30%, p = 0.003). In the 1847 tumors taken from metastatic sites, 40% (746) overexpressed TUBB3 while in 1629 CRCs taken from primary tumors, only 34% (547) overexpressed TUBB3 (p&amp;lt;0.0001). Interestingly, in tumors that overexpressed TUBB3, 65% also overexpressed cMET (828/1275) and 33% also overexpressed TLE3 (431/1299). This compares to 50% cMET expression (1096/2207, p&amp;lt;0.0001) and 23% TLE3 expression (517/2225, p&amp;lt;0.0001) in tumors that were negative for TUBB3. Microsatellite instability detected by fragment analysis was more prevalent in the TUBB3-negative cohort than the TUBB3-positive cohort (7.4% or 77/1046 vs. 2.9% or 16/558, p = 0.0002). Mutations in APC (62% vs. 56%, p = 0.0003) and KRAS (55% vs. 46%, p&amp;lt;0.0001) were more frequent in TUBB3-positive tumors, while GNAS (2% vs. 5%, p&amp;lt;0.0001) and SMAD4 (10.1% vs. 14.6%, p = 0.0005) mutations were significantly more frequent in tumors that were negative for TUBB3 expression. Thus, high expression of TUBB3 was found in 37% of CRCs, and was significantly associated with tumors that originated from the left colon and with tumors taken from metastatic sites. Distinct biomarker features detected by IHC and sequencing suggest that TUBB3 expression may carry theranostic importance which warrants further investigation in clinical trials. Citation Format: Joanne Xiu, Sandeep Reddy, Wafik S. El-Deiry. Expression of class III beta-tubulin (TUBB3) in 3580 colorectal cancers (CRCs) and correlation with clinico-pathological and molecular features. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4923.