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BACKGROUND: OncoBEAM TM RAS CRC kit using BEAMing technology is a circulating tumour DNA (ctDNA) test for detecting plasma RAS mutational status in metastatic colorectal cancer (mCRC). We conducted a multicentre, prospective study to investigate the concordance of the RAS mutational status between plasma ctDNA and tumour tissue DNA. METHODS: mCRC patients without prior anti-EGFR antibodies or regorafenib treatment were enroled. Plasma-and tissue-based RAS mutational status were determined by BEAMing, respectively. RESULTS: A total of 280 patients from eight institutions were eligible. The overall agreement between plasma-and tissue-based analyses was 86.4%, with a positive percent agreement of 82.1% and negative percent agreement of 90.4%. From logistic regression analysis, lung metastasis alone indicated the most significant factor associated with discordance. The agreement between plasma-and tissue-based analyses was 64.5% in patients with lung metastasis alone (n = 31) indicating lower amount of ctDNA. Among the cases with lung metastasis alone, all plasma-and tissue-based analyses were perfectly concordant in cases with ≥20 mm of maximum lesion diameter or ≥10 lesions. CONCLUSION: The clinical validity of OncoBEAM TM RAS CRC kit was confirmed. Careful attention should be paid for mCRC patients with lung metastases alone having fewer metastases or smaller diameter lesions.

Abstract. Phosphatase of regenerating liver (PRL)-3 was identified as a molecule associated with liver metastasis in colorectal cancer (CRC), although its precise causative role in distant metastasis remains elusive from a clinical point of view. The aim of this study was to promote the mechanistic insight of PRL-3 involvement in liver metastasis in CRC. One hundred and seven CRC patients with resection of the primary lesions were studied for clinicopathological and prognostic association with PRL-3 and were evaluated by immunohistochemistry in univariate and multivariate analyses. Intense immunostaining of PRL-3 was found in Dukes' A (0/26), Dukes' B (0/30), Dukes' C (18/30) and Duke's D (20/21) although the PRL-3 expression could not predict metachronous liver metastasis (MLM) in Dukes' C patients. PRL-3 expression showed an inverse correlation of prognosis in a univariate prognostic analysis (P<0.0001), though a multivariate assay failed to demonstrate PRL-3 relevance as an independent prognostic factor. PRL-3 expression was closely associated with classic prognostic factors such as the pN factor (P<0.0001), H factor-synchronous liver metastasis (SLM) (P<0.0001), pT factor (P=0.0002), preoperative CEA (P<0.0001) and preoperative CA19-9 (P<0.0001). Multivariate logistic regression analysis of PRL-3 expression revealed that the pN factor (P<0.0001), CEA (P<0.0001) and CA19-9 (P<0.0001) were finally remnant as an independent association with PRL-3. However, the H factor (SLM) was eliminated. Our data suggested that liver metastasis by PRL-3 is putatively mediated through lymph node metastasis and elevated tumor markers in the serum and the PRL-3 expression may not represent a direct causative mechanism of liver metastasis.

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