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: Henrike Ronneburg, Paul N Span, Eva Kantelhardt, Angela Dittmer, Dario Schunke, Hans-Jürgen Holzhausen, Fred C G J Sweep, Jürgen Dittmer
• Journal: International journal of oncology (Int J Oncol) Vol. 36 Issue 2 Pg. 379-86 (Feb 2010) ISSN: 1791-2423 [Electronic] Greece
• PMID: 20043072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Guanine Nucleotide Dissociation Inhibitors
• rho-Specific Guanine Nucleotide Dissociation Inhibitors
• Cisplatin
• Fluorouracil
• Methotrexate

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Carcinoma, Ductal, Breast (drug therapy, genetics, metabolism)
• Chemotherapy, Adjuvant
• Cisplatin (therapeutic use)
• Drug Resistance, Neoplasm (genetics)
• Female
• Fluorouracil (therapeutic use)
• Guanine Nucleotide Dissociation Inhibitors (biosynthesis)
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Methotrexate (therapeutic use)
• Middle Aged
• Neoplasm Staging
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Treatment Outcome
• rho-Specific Guanine Nucleotide Dissociation Inhibitors