Abstract 3971
Background
Colorectal cancer (CRC) also has various genetic backgrounds and diversity. In addition to the RAS gene, a lot of new knowledge about molecules playing an important role in the process of carcinogenesis or drug resistance, and emerging molecules as targets for new treatments have been reported recently. In this research, we aim to clarify correlation between emerging molecules and differences through clinical stages in CRC usig tissue array.
Methods
Consecutive patients who underwent sugery in our hospital from June 2003 to March 2011 were enrolled in this study. Tissue array based profiling of emerging molecules was performed on archival samples using immunohistochemistry for MLH1/MSH2/MSH6/PMS2, CDX2, HER2 and PD-L1, and fluorescence in situ hybridization for ERBB2. We analyzed the correlation among molecular profile, overall survival, pathological findings and location of CRC.
Results
A total of 1122 CRC from stage 0 to IV were analyzed; details in Table. In dMMR population, the proportion of PD-L1 expression (19.2%) was increased significantly compared to those in pMMR population (2.5%). In the univariate analysis, CDX2 negative, BRAF mutation and poorly differentiated histology and in the multivariate analysis, CDX2 negative, dMMR and poorly differentiated histology were idnetified as predictive factors for OS in whole population.Table:
570P
| All patients (n = 1122) | |
|---|---|
| Median age (±SD) | 65±11.5 |
| Sex, n (%) | |
| −Male | 586(52.2) |
| −Female | 536(47.8) |
| Stage of disease at time of presentation, n (%) | |
| −0 | 26(2.3) |
| −I | 215(19.1) |
| −II | 318(28.3) |
| −III | 348(30.9) |
| −IV | 212(18.8) |
| −Unknown | 3(0.2) |
| Pathology of primary tumor, n (%) | |
| −differentiated | 1024(91.4) |
| −poorly differentiated | 86(7.6) |
| −unknown | 13(1.1) |
| Site of primary tumor, n (%) | |
| −Right sided | 346(30.8) |
| −Left sided | 757(7.6) |
| −Unknown | 22(1.9) |
| Molecular status, n (%) | |
| −dMMR | 78(6.9) |
| −CDX2 negative | 43(3.8) |
| −BRAF V600E mutation by IHC | 35(3.1) |
| −HER2 3+ | 34(3.0) |
| −ERBB2 amplification | 26(2.2) |
| −HER2 3+ and ERBB2 amplification | 23(2.0) |
| −PD-L1 positive | 41(3.6) |
Conclusions
Our data comprehensively summarized the significance of the recent emerging molecules in CRC over the clinical stages. These are considered to contribute to precision medicince in near future.
Clinical trial identification
Legal entity responsible for the study
Ethical Guidelines for Medical Research on Humans
Funding
None
Disclosure
E. Shinozaki: Honoraria from Taiho, Merck Serono, Chugai, Yakult, Ono, Takeda, Bayer and Lilly. All other authors have declared no conflicts of interest.