Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance

Folate receptor alpha (FR alpha), encoded by folate receptor 1 (adult) gene, has emerged as a cancer biomarker and potential therapeutic target. In addition, its expression in tumors may offer prognostic information. The aim of this study was to assess the prognostic value of FR alpha expression and other common molecular markers in resected liver metastases from colorectal cancer. To maximize potential biological differences, we selected two groups of patients with markedly different outcomes as study subjects. Immunohistochemical analysis of FR alpha expression and other common markers (thymidylate synthase, p53, p27, BCL2, ki67, MLH1, MSH2 and MGMT) on tissue microarrays was carried out on samples from 160 patients; 56 patients survived at least 10 years following liver resection, and 104 died within 2 years of surgery. These markers were evaluated and compared with standard clinical predictors of outcome including a previously validated clinical risk score. Our results showed that in addition to known clinical risk factors, FR alpha positivity was significantly associated with the early death group (32% compared with 13%; P=0.03). None of the other common molecular markers were differentially expressed between the two groups. On multivariate analysis, clinical risk score, margin status and FR alpha expression were independently associated with outcome. Specific multivariate comparisons confirmed that FR alpha expression was associated with outcome independent of the clinical risk score and margin. These data demonstrate that FR alpha expression is present in a subset of resected hepatic colorectal cancer metastases, and this marker is independently associated with survival after hepatic resection. The prognostic value of FR alpha expression and the utility of FR alpha-targeted therapies in stage-IV colorectal cancer patients deserve further exploration. Modern Pathology (2011) 24, 1221-1228; doi:10.1038/modpathol.2011.82; published online 13 May 2011