MyD88 predicts chemoresistance to paclitaxel in epithelial ovarian cancer.
BACKGROUND
Early identification of chemoresistance in patients with ovarian cancer is of utmost importance in order to provide them with the most appropriate therapy. Recently, we described the expression of MyD88 in ovarian cancer cells that were resistant to the cytotoxic agent paclitaxel. In addition to chemoresistance, in MyD88 positive ovarian cancer cells, paclitaxel stimulates growth and production of proinflammatory cytokines. The objective of this study was to determine the correlation of MyD88 expression in primary and recurrent epithelial ovarian cancers with the response to carboplatin and paclitaxel combination chemotherapy.


METHODS
Tumors are heterogeneous structures that contain different cell populations, thus rendering the identification of specific tumor markers difficult. Using laser capture microdissection, pure cancer cells were isolated from ovarian malignant tumors that were obtained from 20 patients at the time of surgery. The microdissected cells were evaluated for the expression of MyD88, FasL, and XIAP by western blot analysis.


RESULTS
Protein expression was observed in samples containing as low as 500 cells. The results were correlated with the clinical course of those patients. It was evident that MyD88 expression in ovarian cancer cells accurately predicts a poor response to paclitaxel chemotherapy as shown by a short progression-free interval and overall survival.


CONCLUSIONS
We describe for the first time a molecular approach to identify paclitaxel chemoresistance. Toxicity from agents without therapeutic benefit can be avoided by identifying those patients who will not respond to a specific agent. Molecular markers will enable us to design individualized treatments and improve overall survival.
Silasi
Dan-Arin
DA
Department of Obstetrics, Gynecology, and Reproductive Services, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Alvero
Ayesha B
AB
Illuzzi
Jessica
J
Kelly
Michael
M
Chen
Rui
R
Fu
Han-Hsuan
HH
Schwartz
Peter
P
Rutherford
Thomas
T
Azodi
Masoud
M
Mor
Gil
G
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007834:Lasers; D042282:Microdissection; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D017239:Paclitaxel