title: Nuclear Maspin expression is associated with response to adjuvant 5-fluorouracil based chemotherapy in patients with stage III colon cancer.
abstract: Maspin, a member of the Serpin protease inhibitor family, is overexpressed in poorly differentiated colorectal tumors and more frequently found in tumors with microsatellite instability. Immunohistochemical nuclear Maspin staining is predominantly seen in tumor cells at the invasion front of such cancers, suggesting that this molecule is associated with local tumor cell infiltration and aggressiveness. In a retrospective study, we studied nuclear Maspin expression as a potential prognostic tool in a total of 172 primary stage III colon cancers by immunohistochemistry. Of those 172 patients, 76 were treated by surgery only, and 96 patients received additional adjuvant 5-fluorouracil (5-FU) based chemotherapy. Nuclear Maspin expression was an independent adverse prognostic factor for overall survival in our patient cohort (hazard ratio 2.08; 95% CI, 1.13-3.81; p = 0.018). However, patients with primary tumors expressing Maspin in the nucleus showed a significant treatment benefit from 5-FU chemotherapy (hazard ratio 0.384; 95% CI, 0.188-0.784; p = 0.009) compared to adjuvantly treated patients whose tumors did not express this molecule. Nuclear Maspin expression is highly predictive of 5-FU chemotherapy response in patients with advanced stage colon cancer. Patients with negative immunohistochemical Maspin expression do not benefit from 5-FU treatment and may be candidates for an alternative (non-5-FU based) adjuvant therapy regime.
authors.affiliation: Department of Pathology and Molecular Diagnostics, University of Regensburg, Germany. wolfgang.dietmaier@klinik.uni-regensburg.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Marcus
authors.initials: M
authors.lastname: Bettstetter
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.forename: Matthias
authors.initials: M
authors.lastname: Woenckhaus
authors.forename: Petra
authors.initials: P
authors.lastname: Rümmele
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Dechant
authors.forename: Hagen
authors.initials: H
authors.lastname: Blaszyk
authors.forename: Armin
authors.initials: A
authors.lastname: Pauer
authors.forename: Monika
authors.initials: M
authors.lastname: Klinkhammer-Schalke
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstädter
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002467:Cell Nucleus; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015843:Serpins / Q000032:analysis / Q000096:biosynthesis*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C085344:SERPIN-B5; D015843:Serpins; D005472:Fluorouracil