Abstract LB-171: Concordance between protein expression and mRNA expression in the large cohort of cancer patients
Authors: Ghazalpour Anatole , Chen Wangjuh Sting , Wen Wenhsiang , Gatalica Zoran , Bender Ryan 
Published: May 2015

Introduction: Immunohistochemical (IHC) analysis of protein expression in clinical specimens has been invaluable in diagnosing, monitoring and guiding treatment in cancer patients. This approach, however, has its limitations including the difficulty to obtain robust and reliable antibodies, the semi quantitative nature of the assay, subjectivity of intensity call, and the lack of specificity to detect clinically relevant isoform expression in tumor specimen. In light of these limitations, RNA expression may be a useful replacement or a complementary approach to IHC in clinical settings. In this study, we compared the concordance between IHC and mRNA expression levels as measured by microarray using a large cohort of cancer patients spanning multiple lineages.

Methods: 10246 patient samples that included 40 tumor types were utilized in this study. Transcript and protein expression levels were measured for ESR1, AR, KIT, ERBB2 (Her2), RRM1, and ERCC1. Transcript levels were measured by Illumina's HumanHT-12 microarray (v4), and IHC was performed using the following antibodies: SP1 (ESR1), AR27 (AR), 4B5 (Her2), 8F1 (ERCC1), anti-CD117 polyclonal (KIT), and 10526-1-AP (RRM1).

Results: We observed a significant correlation between ERBB2, ESR1, and KIT with IHC data. Of the 3 probes on the microarray measuring ERBB2, only one probe mapping to the 3’ end of the two ERBB2 isoforms showed significant association with IHC data. For KIT, IHC and mRNA expression correlated well across, thymic carcinomas, poorly differentiated neuroendocrine tumors, melanoma, GIST, and head and neck cancer. For ESR1, significant correlations were observed for uterine sarcoma, endometrial carcinoma, and breast adenocarcinoma. Cervical cancers and ovarian surface epithelial carcinomas showed diminished association, and there was a lack of association in NSCLC and neuroendocrine carcinoid tumors. For AR, we observed strong correlation only in prostate tumors. ERCC1 and RRM1 mRNA expressions did not correlate well with protein expression in any of the tumor lineages examined.

Conclusion: These observations suggest that measuring mRNA via microarray has the potential to serve as a surrogate for IHC in clinical setting. The mixed associations observed for some of the genes exhibited lineage specificity suggesting that the relation between microarray results and IHC may be driven by the tissue-specific expression of isoforms, differential expression of genes in the stromal cells, and the technical limitations of each platform including the specificity of either the probes used to measure mRNA or antibodies used to measure protein expression. As such, combining the two platforms in the clinical setting may provide a more complete assessment of gene expression in tumor samples.

Citation Format: Anatole Ghazalpour, Wangjuh Sting Chen, Wenhsiang Wen, Zoran Gatalica, Ryan Bender. Concordance between protein expression and mRNA expression in the large cohort of cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-171. doi:10.1158/1538-7445.AM2014-LB-171