title: Predictive markers of chemoradiotherapy for rectal cancer: comparison of biopsy specimens taken before and about 1 week after the start of chemoradiotherapy.
abstract: BACKGROUND
  Preoperative chemoradiotherapy (CRT) significantly decreases local recurrence in patients with rectal cancer. Although various biomarkers in biopsy specimens obtained before starting CRT have been examined, reliable prognostic factors have yet to be established. We tested the hypothesis that biopsy specimens obtained soon after the start of CRT can be used as prognostic factors.
  
  
  METHODS
  Preoperative CRT was given to 70 consecutive patients with rectal cancer. Biopsies were taken before and about 7 days after starting CRT. The specimens were stained with hematoxylin and eosin (HE), and the expressions of Ki67, p53, and p21 and apoptosis were evaluated immunohistochemically.
  
  
  RESULTS
  The expressions of Ki67, p53, and p21 and apoptosis before treatment were not significantly related to histologic response or tumor shrinkage. In specimens obtained about 7 days after CRT began, marked histologic regression was significantly higher in p21-positive, apoptosis-positive cases, and in cases with moderate changes on HE specimens (p = 0.017, p = 0.010, and p = 0.004, respectively). The tumor shrinkage was significantly higher in apoptosis-positive cases and cases with moderate changes on HE specimens (p = 0.002 and p < 0.001, respectively). Disease-free survival (DFS) was significantly higher in patients who had marked regression than in those who did not (p = 0.019). DFS was also significantly higher in patients with moderate changes on HE specimens than in those with mild changes (p = 0.016).
  
  
  CONCLUSIONS
  Changes on HE-stained biopsy specimens obtained about 1 week after starting CRT are a reliable prognostic factor, similar to histologic marked regression in resected specimens; a major advantage is that the former results are available at an early phase.
authors.affiliation: Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. tsuzuki@is.icc.u-tokai.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Sadahiro
authors.affiliation: Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Kazutake
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Gota
authors.initials: G
authors.lastname: Saito
authors.affiliation: Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Kamijo
authors.affiliation: Department of Radiology, Tokai University, Isehara, Kanagawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akiba
authors.affiliation: Department of Radiology, Tokai University, Isehara, Kanagawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kawada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001706:Biopsy; D059186:Chemoradiotherapy, Adjuvant; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012004:Rectal Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000628:therapy; D012007:Rectum / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53
keywords: Chemoradiotherapy; Prognostic factor; Rectal cancer
references.citation: J Clin Oncol. 2004 May 1;22(9):1572-82
references.pmid: 15117979
references.citation: J Clin Oncol. 2006 Oct 1;24(28):4620-5
references.pmid: 17008704
references.citation: J Clin Oncol. 2012 Jun 1;30(16):1926-33
references.pmid: 22529255
references.citation: Cancer Res. 1994 Mar 1;54(5):1169-74
references.pmid: 8118801
references.citation: Colorectal Dis. 2012 May;14(5):555-61
references.pmid: 21689364
references.citation: N Engl J Med. 2006 Sep 14;355(11):1114-23
references.pmid: 16971718
references.citation: Jpn J Clin Oncol. 2004 Dec;34(12):740-6
references.pmid: 15640505
references.citation: Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):673-88
references.pmid: 19480968
references.citation: Int J Radiat Oncol Biol Phys. 2002 Feb 1;52(2):294-303
references.pmid: 11872273
references.citation: Ann Surg. 2007 Nov;246(5):693-701
references.pmid: 17968156
references.citation: Cell. 1993 Sep 24;74(6):957-67
references.pmid: 8402885
references.citation: Hum Pathol. 2005 Apr;36(4):364-71
references.pmid: 15891997
references.citation: J Cell Physiol. 2000 Mar;182(3):311-22
references.pmid: 10653597
references.citation: J Clin Oncol. 1995 Jun;13(6):1417-24
references.pmid: 7751887
references.citation: World J Gastroenterol. 2008 Feb 21;14(7):1060-6
references.pmid: 18286688
references.citation: Cancers (Basel). 2011 Apr 26;3(2):2176-94
references.pmid: 24212803
references.citation: Int J Radiat Oncol Biol Phys. 1997 Feb 1;37(3):619-27
references.pmid: 9112461
references.citation: Cancer Res. 1995 May 15;55(10):2075-80
references.pmid: 7743505
references.citation: Ann Surg Oncol. 2001 Jun;8(5):418-24
references.pmid: 11407516
references.citation: Br J Cancer. 2009 Jul 7;101(1):116-23
references.pmid: 19491899
references.citation: Anticancer Res. 2004 Mar-Apr;24(2C):1217-21
references.pmid: 15154650
references.citation: Dis Colon Rectum. 2001 Nov;44(11):1689-95
references.pmid: 11711743
references.citation: J Clin Oncol. 2012 May 20;30(15):1770-6
references.pmid: 22493423
references.citation: Ann Surg Oncol. 2010 Jul;17(7):1758-66
references.pmid: 20131015
references.citation: Cancer. 1991 Aug 1;68(3):517-23
references.pmid: 2065270
references.citation: Anticancer Res. 2004 Sep-Oct;24(5B):3161-7
references.pmid: 15510606
references.citation: Surg Oncol. 2006 Dec;15(4):211-6
references.pmid: 17360176
references.citation: Cancer. 1994 Jun 1;73(11):2680-6
references.pmid: 8194005
references.citation: Int J Oncol. 2002 Oct;21(4):787-93
references.pmid: 12239617
references.citation: Dig Liver Dis. 2010 Oct;42(10):679-84
references.pmid: 20227932
references.citation: Lancet Oncol. 2010 Sep;11(9):835-44
references.pmid: 20692872
references.citation: Eur J Surg Oncol. 2004 Sep;30(7):750-8
references.pmid: 15296989
references.citation: Br J Cancer. 2008 Jan 15;98(1):143-7
references.pmid: 18087284
references.citation: Br J Cancer. 2002 Mar 4;86(5):744-9
references.pmid: 11875737
references.citation: J Clin Oncol. 2003 Sep 15;21(18):3391-401
references.pmid: 12885834
references.citation: Cancer Res. 1994 Nov 15;54(22):5824-30
references.pmid: 7954409
references.citation: Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1455-61
references.pmid: 17445998