title: PTEN expression is consistent in colorectal cancer primaries and metastases and associates with patient survival.
abstract: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates the phosphoinositide-3-kinase (PI3K) signaling pathway. In colorectal cancer (CRC), observed frequencies of loss of PTEN expression, concordant expression in primary tumors and metastases, and the association of PTEN status with outcome vary markedly by detection method. We determined the degree to which PTEN expression is consistent in 70 matched human CRC primaries and liver metastases using a validated immunohistochemistry assay. We found loss of PTEN expression in 12.3% of assessable CRC primaries and 10.3% of assessable liver metastases. PTEN expression (positive or negative) was concordant in 98% of matched colorectal primaries and liver metastases. Next we related PTEN status to mutations in RAS and PI3K pathway genes (KRAS, NRAS, BRAF , and PIK3CA) and to overall survival (OS). PTEN expression was not significantly associated with the presence or absence of mutations in RAS or PI3K pathway genes. The median OS of patients whose tumors did not express PTEN was 9 months, compared to 49 months for patients whose tumors did express PTEN (HR = 6.25, 95% confidence intervals (CI) (1.98, 15.42), P = 0.0017). The association of absent PTEN expression with increased risk of death remained significant in multivariate analysis (HR = 6.31, 95% CI (2.03, 17.93), P = 0.0023). In summary, PTEN expression was consistent in matched CRC primaries and in liver metastases. Therefore, future investigations of PTEN in metastatic CRC can use primary tumor tissue. In patients with liver-only metastases, loss of PTEN expression predicted poor OS.
authors.affiliation: Department of Internal Medicine Division of Hematology/Oncology Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, California, USA.
authors.forename: Chloe E
authors.initials: CE
authors.lastname: Atreya
authors.forename: Zaina
authors.initials: Z
authors.lastname: Sangale
authors.forename: Nafei
authors.initials: N
authors.lastname: Xu
authors.forename: Mary R
authors.initials: MR
authors.lastname: Matli
authors.forename: Eliso
authors.initials: E
authors.lastname: Tikishvili
authors.forename: William
authors.initials: W
authors.lastname: Welbourn
authors.forename: Steven
authors.initials: S
authors.lastname: Stone
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.forename: Robert S
authors.initials: RS
authors.lastname: Warren
mesh_terms: D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Biomarker; PTEN; colorectal cancer; concordance; survival