title: Prognostic value of Ki-67 expression in conversion therapy for colorectal liver-limited metastases.
abstract: BACKGROUND
  The objective of this study was to examine the prognostic value of Ki-67 expression in conversion therapy for colorectal liver-confined metastases.
  
  
  METHODS
  We enrolled a total of 96 patients including 54 patients who received oxaliplatin- or irinotecan-based chemotherapy and curative hepatectomy for initially unresectable metastases (conversion group) and 42 patients with initially resectable liver metastases (straight hepatectomy group). Ki-67 expression was examined in 96 resected specimens but excluded the 2 specimens that revealed no residual cancer cells in conversion group.
  
  
  RESULTS
  Conversion therapy leads to greater survival that is equivalent to that straight hepatectomy group. In conversion group, high Ki-67 expression (> 30%) levels were detectable in 33 patients (64%) after chemotherapy prior to conversion therapy. High Ki-67 expression was significantly associated with shorter disease-free survival and worse overall survival (P < 0.01 in both), and was an independent worse prognostic factor of disease-free survival and overall survival (hazard ratio [HR] and P-values were 5.608, 0.001 and 5.366, 0.04, respectively) in patients with conversion therapy. Interestingly, even in the patients with RECIST PR (n = 32), high Ki-67 expression was significantly shorter disease-free survival compared to low Ki-67 expression (P < 0.001). In contrast to conversion group, there was no significant difference in disease free survival and overall survival between low (n = 14, 33%) and high (n = 28, 67%) Ki-67 expressions in patients with straight hepatectomy (P = 0.14 and 0.74, respectively).
  
  
  CONCLUSIONS
  Residual Ki-67 expression is a useful biomarker for worse prognostic outcomes after conversion therapy. High Ki-67 expression may be a biomarker of micrometastases containing aggressive cancer cells.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Beppu
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nitta
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Chikamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
keywords: Colorectal cancer; Ki-67 index; conversion therapy; liver metastasis