title: Clinical significance of fibroblast growth factor receptor 2 expression in patients with residual rectal cancer after preoperative chemoradiotherapy: relationship with KRAS or BRAF mutations and MSI status.
abstract: This study was designed to determine the prognostic impact and clinical significance of FGFR2 in residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were analyzed. To evaluate FGFR2 expression, immunohistochemistry was performed on whole section tissues. KRAS exon 2 (codon 12 and 13), BRAF V600E mutational status, and microsatellite instability (MSI) were determined using polymerase chain reactions. Of the eligible 141 patients, FGFR2 over-expression was observed in 75.9 % (n = 107) and was correlated with perineural invasion (P = 0.005) and inferior tumor regression grading (TRG) (P = 0.009). However, FGFR2 expression had no relationship with KRAS and BRAF mutation results or with MSI results. On univariate analysis, FGFR2 over-expression was significantly associated with worse rectal cancer-specific survival (RCSS) (P = 0.005) and disease-free survival (DFS) (P = 0.035). However, multivariate analysis revealed that FGFR2 over-expression was not independently associated with RCSS and DFS (all P > 0.05). Although FGFR2 over-expression did not independently influence patient outcome, FGFR2 over-expression was associated with worse prognosis and inferior TRG. Our data may aid in understanding the therapeutic approaches targeting FGFR2 in patients with residual rectal cancer after preoperative CRT.
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea.|Department of Pathology, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea.
authors.forename: Ghilsuk
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea.
authors.forename: Hwayoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Pathology, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Keun
authors.initials: K
authors.lastname: Hur
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea. san_0729@naver.com.|Department of Pathology, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea. san_0729@naver.com.|Department of Pathology, Kyungpook National University Hospital, Daegu, Republic of Korea. san_0729@naver.com.
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D059186:Chemoradiotherapy, Adjuvant; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis*; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Fibroblast growth factor receptor 2; KRAS; Microsatellite instability; Preoperative chemoradiotherapy; Prognosis; Rectal cancer
references.citation: J Clin Oncol. 2012 Jun 1;30(16):1926-33
references.pmid: 22529255
references.citation: Eur J Cancer. 2007 Nov;43(17):2612-20
references.pmid: 17949968
references.citation: Mol Cancer Ther. 2015 Oct;14(10):2292-302
references.pmid: 26294741
references.citation: Cancer. 2008 Jul 1;113(1):57-64
references.pmid: 18442099
references.citation: Mod Pathol. 2011 Nov;24(11):1500-10
references.pmid: 21725289
references.citation: Ann Surg Oncol. 2015 Feb;22(2):513-9
references.pmid: 25145505
references.citation: J Clin Oncol. 2005 Dec 1;23(34):8688-96
references.pmid: 16246976
references.citation: Patholog Res Int. 2012;2012:574768
references.pmid: 22701813
references.citation: Nature. 2007 Jun 28;447(7148):1087-93
references.pmid: 17529967
references.citation: Clin Cancer Res. 2013 May 1;19(9):2572-83
references.pmid: 23493349
references.citation: Ann Surg Oncol. 2007 Oct;14(10):2766-72
references.pmid: 17551794
references.citation: Tumour Biol. 2016 Mar;37(3):3571-80
references.pmid: 26456957
references.citation: Lancet Oncol. 2015 Jun;16(6):686-94
references.pmid: 25981814
references.citation: Eur J Cancer. 2013 Jan;49(1):82-9
references.pmid: 22909998
references.citation: Virchows Arch. 2014 Nov;465(5):547-58
references.pmid: 25086725
references.citation: Nat Rev Cancer. 2010 Feb;10(2):116-29
references.pmid: 20094046
references.citation: Mol Cancer Ther. 2012 Sep;11(9):2010-20
references.pmid: 22778155
references.citation: Future Oncol. 2009 Feb;5(1):27-32
references.pmid: 19243295
references.citation: Cancer Lett. 2011 Aug 1;307(1):47-52
references.pmid: 21482024
references.citation: Virchows Arch. 2015 Jun;466(6):645-54
references.pmid: 25739551
references.citation: N Engl J Med. 2004 Oct 21;351(17):1731-40
references.pmid: 15496622
references.citation: Cancer Lett. 2011 Oct 28;309(2):209-19
references.pmid: 21745712
references.citation: Ann Surg Oncol. 2014 May;21(5):1561-8
references.pmid: 24385208
references.citation: Oncogene. 1997 Dec 18;15(25):3059-65
references.pmid: 9444954
references.citation: PLoS One. 2012;7(2):e30801
references.pmid: 22383975
references.citation: J Clin Pathol. 2014 Dec;67(12):1056-61
references.pmid: 25271212
references.citation: Korean J Pathol. 2014 Aug;48(4):276-82
references.pmid: 25214859
references.citation: Pathol Res Pract. 2011 Dec 15;207 (12 ):762-8
references.pmid: 22070922