BACKGROUND: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo is not well understood. MATERIALS AND METHODS: hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). RESULTS: No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p < 0.001) in partially responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p = 0.059) in tumors treated with four or more courses of Pt-chemo. CONCLUSION: A change in hMLH1 MET is a major molecular cause of acquired resistance to Pt-chemo in EOC.
BACKGROUND: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo is not well understood. MATERIALS AND METHODS:hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). RESULTS: No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p < 0.001) in partially responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p = 0.059) in tumors treated with four or more courses of Pt-chemo. CONCLUSION: A change in hMLH1 MET is a major molecular cause of acquired resistance to Pt-chemo in EOC.
Authors: Bryan J Schneider; Manish A Shah; Kelsey Klute; Allyson Ocean; Elizabeta Popa; Nasser Altorki; Michael Lieberman; Andrew Schreiner; Rhonda Yantiss; Paul J Christos; Romae Palmer; Daoqi You; Agnes Viale; Pouneh Kermani; Joseph M Scandura Journal: Clin Cancer Res Date: 2016-11-10 Impact factor: 12.531
Authors: Siqing Fu; Wei Hu; Revathy Iyer; John J Kavanagh; Robert L Coleman; Charles F Levenback; Anil K Sood; Judith K Wolf; David M Gershenson; Maurie Markman; Bryan T Hennessy; Razelle Kurzrock; Robert C Bast Journal: Cancer Date: 2010-11-08 Impact factor: 6.860
Authors: Robert Brown; Edward Curry; Luca Magnani; Charlotte S Wilhelm-Benartzi; Jane Borley Journal: Nat Rev Cancer Date: 2014-09-25 Impact factor: 60.716