Abstract 1201: PTEN null expression is concordant in colorectal cancer primaries and metastases and associates with poor survival.
Authors: Atreya Chloe E. , Sangale Zaina , Xu Nafei , Matli Mary R. , Tikishvili Eliso , Welbourn William , Stone Steve , Shokat Kevan M. , Warren Robert S. 
Published: August 2014

Background: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a negative regulator of the phosphoinositide-3-kinase (PI3K) survival pathway. In colorectal cancer, the method of detection is relevant in determining the frequency of loss of PTEN and the association of PTEN status with outcome. Earlier studies reported discordant PTEN expression in an average of 1 in 3 matched colorectal primaries and metastases. Ours is the first investigation of PTEN concordance using a standardized immunohistochemistry assay.

Objectives: Our primary aim was to determine the level of concordant PTEN expression in matched human colorectal primaries and liver metastases using a robust assay. Secondary aims were to relate PTEN status to oncogenic mutations in the RAS and PI3K pathways, and to overall survival.

Experimental Design: We used a standardized immunohistochemistry assay and a reproducible method of interpretation to characterize PTEN expression in paired colorectal primaries and liver metastases collected from 70 patients. Mutational hotspots in KRAS, NRAS, BRAF and PIK3CA were sequenced.

Results: 7 patients were excluded due to insufficient primary tumor. PTEN null expression was found in 7 of 62 assessable colorectal primaries (12.3%) and 6 of 58 assessable liver metastases (10.3%). PTEN expression (positive or null) was concordant in 98% of matched primaries and liver metastases. There was no significant association between PTEN status and RAS family or PIK3CA mutations. The median overall survival of patients with PTEN null tumors was 9 months, compared to 49 months with PTEN expressing tumors (HR=6.25, 95% CI (1.98, 15.42), p = 0.0017). The association of increased risk of death with PTEN null expression remained significant in multivariate analysis (HR=6.31, 95% CI (2.03, 17.93), p = 0.0023).

Conclusion: PTEN status was highly concordant in matched colorectal primaries and liver metastases. Loss of PTEN expression predicted poor overall survival.

Concordance of PTEN, PIK3CA, RAS, and BRAF in paired colorectal primaries and liver metastases PRIMARIES PTEN PIK3CA RAS/BRAF (−),(+),equivocal WT, Mut WT, Mut METASTASES PTEN null (−) 6, 0, 0 PIK3CA wild-type 54, 0 RAS/BRAF wild-type 29, 1 PTEN positive (+) 1, 43, 5 PIK3CA mutant 2, 5 RAS/BRAF mutant 0, 31 PTEN equivocal 0, 2, 0 CONCORDANCE 98%(86% including equivocal) 96.7% 98.4%

Citation Format: Chloe E. Atreya, Zaina Sangale, Nafei Xu, Mary R. Matli, Eliso Tikishvili, William Welbourn, Steve Stone, Kevan M. Shokat, Robert S. Warren. PTEN null expression is concordant in colorectal cancer primaries and metastases and associates with poor survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1201. doi:10.1158/1538-7445.AM2013-1201