title: FANCD2 expression in advanced non-small-cell lung cancer and response to platinum-based chemotherapy.
abstract: Fanconi's anemia (FA) is a genetically heterogeneous disease characterized by cancer susceptibility and hypersensitivity to cross-linking agents such as cisplatin. Recently, inactivation of the FA pathway has been proposed to contribute to genomic instability and an increased sensitivity to cisplatin-based therapy in a subset of ovarian tumors. Platinum-based chemotherapy constitutes standard systemic therapy for advanced non-small-cell lung cancer (NSCLC), but resistance to platinum chemotherapy is common. In this study, we evaluated the status of the FA pathway in tumor samples derived from patients with NSCLC in relation to their response to platinum-based chemotherapy. For this purpose, we assessed the expression of FANCD2 protein (a marker for FA pathway functioning) by immunohistochemistry in tumor specimens from 47 patients treated with platinum-based chemotherapy. FANCD2 expression could be detected in 32% of the cases (15 of 47). Expression of FANCD2 was not correlated with any patient or tumor characteristics, and FANCD2 expression was not a predictor of response to chemotherapy or patient survival. In conclusion, the activation status of the FA pathway had no value in predicting sensitivity to platinum-based chemotherapy in patients with advanced NSCLC.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ferrer
authors.forename: Simone W
authors.initials: SW
authors.lastname: Span
authors.forename: Barbara
authors.initials: B
authors.lastname: Vischioni
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Johan P
authors.initials: JP
authors.lastname: de Winter
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Frank A E
authors.initials: FA
authors.lastname: Kruyt
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D052236:Fanconi Anemia Complementation Group D2 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins; D002945:Cisplatin