title: Assessment of SMAD4, p53, and Ki-67 alterations as a predictor of liver metastasis in human colorectal cancer.
abstract: OBJECTIVE
  The liver is the most common site of metastasis in patients with colorectal cancer (CRC), and this is a determinant of the prognosis. However, no reliable molecular predictors of liver metastasis have yet been identified.
  
  
  METHODS
  Sixty-two surgical specimens of colorectal cancer were studied. The first group included 25 patients who achieved a disease-free survival period of at least 6 years (CRC-M0), and the second group included 37 patients with synchronous (n = 22) or metachronous (n = 15) liver metastasis (CRC-M1). SMAD4, p53, and Ki-67 expression levels were assessed immunohistochemically.
  
  
  RESULTS
  The loss of SMAD4 expression and elevated Ki-67 expression were found significantly more frequently in CRC-M1 patients than in CRC-M0 patients (P = 0.0047 and P = 0.013, respectively). Statistically significant differences were also observed between the CRC-M0 group and the metachronous metastasis group. No difference was seen in the overexpression of p53 between the groups. A combination analysis of SMAD4 and Ki-67 revealed no cases with maintained levels of SMAD4 and a low Ki-67 expression had or developed liver metastasis.
  
  
  CONCLUSIONS
  The loss of SMAD4 expression and elevated Ki-67 expression was therefore found to significantly correlate with liver metastasis, regardless of the time of occurrence, thus indicating these factors to be predictive markers for liver metastasis in patients with CRC.
authors.affiliation: Department of Surgery, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Kawakami
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Michiya
authors.initials: M
authors.lastname: Yasutome
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Funata
authors.forename: Takeo
authors.initials: T
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D051901:Smad4 Protein / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D051901:Smad4 Protein; D016159:Tumor Suppressor Protein p53