title: Microsatellite instability is not related to response to cisplatin-based chemotherapy in cervical cancer.
abstract: This study investigates whether microsatellite instability (MSI) due to defects of the mismatch repair (MMR) system could be associated with response to cisplatin-based neoadjuvant chemotherapy (NACT) and if cisplatin exposure could select MSI-positive cell clones in cervical cancer. Microsatellite analysis was performed by polymerase chain reactions using six microsatellite markers, while hMLH1 protein expression was investigated by immunohistochemistry. We found that 1 tumor out of 20 (5%) NACT-responding patients and 1 tumor out of 18 (6%) nonresponding patients showed MSI. The analysis of tumor specimens collected after NACT revealed no change in the banding pattern as compared to each corresponding pre-NACT tumor at each locus tested. hMLH1 staining was observed in at least > or =80% of cells in all tumors examined except the two exhibiting MSI. Our data showed that MSI due to defects of the MMR system seems not to play a crucial role in the biology of human cervical cancer cells and that MSI seems not to be related to response to chemotherapy. Moreover, cisplatin exposure did not seem to select for MMR-deficient tumor clones in cervical cancer.
authors.affiliation: Department of Gynecology, Catholic University, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ercoli
authors.forename: G
authors.initials: G
authors.lastname: Ferrandina
authors.forename: M
authors.initials: M
authors.lastname: Genuardi
authors.forename: G F
authors.initials: GF
authors.lastname: Zannoni
authors.forename: L
authors.initials: L
authors.lastname: Cicchillitti
authors.forename: G
authors.initials: G
authors.lastname: Raspaglio
authors.forename: S
authors.initials: S
authors.lastname: Carrara
authors.forename: S
authors.initials: S
authors.lastname: Mancuso
authors.forename: G
authors.initials: G
authors.lastname: Scambia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D016022:Case-Control Studies; D043171:Chromosomal Instability; D002945:Cisplatin / Q000494:pharmacology*; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1; D002945:Cisplatin