title: Liver metastasis of colorectal cancer by protein-tyrosine phosphatase type 4A, 3 (PRL-3) is mediated through lymph node metastasis and elevated serum tumor markers such as CEA and CA19-9.
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.
authors.affiliation: Department of Surgery, Kitasato University, Kanagawa, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hatate
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hirai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Sato
authors.forename: Heita
authors.initials: H
authors.lastname: Ozawa
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Wataru
authors.initials: W
authors.lastname: Onozato
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Kokuba
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ihara
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases