title: Rho GDP dissociation inhibitor alpha expression correlates with the outcome of CMF treatment in invasive ductal breast cancer.
abstract: Rho-GDIalpha is an inhibitor of Rho-GTPases, which is involved in cancer progression. Little is known about its role in breast cancer progression. There is evidence, that Rho-GDIalpha may modulate drug resistance of breast cancer cells. To assess the importance of Rho-GDIalpha as a risk factor in invasive ductal breast cancer, cancer specimens of three groups of patients were analyzed for Rho-GDIalpha RNA (group 1, N=72 and group 2, N=73) or protein expression (group 3, N=90). In group 1, patients did not receive any adjuvant treatment, whereas, in groups 2 and 3, patients were treated with anti-estrogens and/or with chemotherapeutical drugs. Rho-GDIalpha RNA levels, measured by RT-PCR from fresh-frozen material, did not correlate with relapse-free survival in Kaplan-Meier analysis, except in a subgroup of CMF-only treated patients. In this subgroup, higher Rho-GDIalpha RNA levels were significantly associated with more favorable prognosis. Immunohistochemical analysis (group 3) confirmed the link between higher Rho-GDIalpha expression and better outcome. This was again particularly true for the CMF-only treated patients. Cox regression analysis revealed that high Rho-GDIalpha protein expression reduced the risk for a relapse by approximately 3-fold, even if adjusted for grading, tumor size, nodal and estrogen receptor (ER) status. The data suggest that Rho-GDIalpha is beneficial to patients who received adjuvant chemotherapy. Rho-GDIalpha is possibly a useful biomarker to predict the response of breast cancer patients to CMF treatment.
authors.affiliation: Klinik für Gynäkologie, Universität Halle, Halle, Saale, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Ronneburg
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Eva
authors.initials: E
authors.lastname: Kantelhardt
authors.forename: Angela
authors.initials: A
authors.lastname: Dittmer
authors.forename: Dario
authors.initials: D
authors.lastname: Schunke
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Holzhausen
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dittmer
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016896:Treatment Outcome; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: D014408:Biomarkers, Tumor; D020730:Guanine Nucleotide Dissociation Inhibitors; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate