title: Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with increased risk of treatment failure using standard chemotherapy protocols.
abstract: BACKGROUND
  The mechanisms responsible for chemoresistance in patients with refractory classical Hodgkin lymphoma (CHL) are unknown. ATP-binding cassette (ABC) transporters confer multidrug resistance in various cancers and ABCC1 overexpression has been shown to contribute to drug resistance in the CHL cell line, KMH2.
  
  
  RESULTS
  We analyzed for expression of five ABC transporters ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2 using immunohistochemistry in 103 pre-treatment tumor specimens obtained from patients with CHL. All patients received first-line standard chemotherapy with doxorubicin (Adriamycin®), bleomycin, vinblastine, and dacarbazine (ABVD) or equivalent regimens. ABCC1 was expressed in Hodgkin and Reed-Sternberg (HRS) cells in 16 of 82 cases (19.5%) and ABCG2 was expressed by HRS cells in 25 of 77 cases (32.5%). All tumors were negative for ABCB1, ABCC2 and ABCC3. ABCC1 expression was associated with refractory disease (p = 0.01) and was marginally associated with poorer failure-free survival (p = 0.06). Multivariate analysis after adjusting for hemoglobin and albumin levels and age showed that patients with CHL with HRS cells positive for ABCC1 had a higher risk of not responding to treatment (HR = 2.84, 95%, CI: 1.12-7.19 p = 0.028).
  
  
  CONCLUSIONS
  Expression of ABCC1 by HRS cells in CHL patients predicts a higher risk of treatment failure and is marginally associated with poorer failure-free survival using standard frontline chemotherapy regimens.
authors.affiliation: Department of Hematopathology, Unit 72, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Greaves
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sanchez-Espiridion
authors.forename: Kranthi
authors.initials: K
authors.lastname: Kunkalla
authors.forename: Kunal S
authors.initials: KS
authors.lastname: Dave
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Liang
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Singh
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Francisco
authors.initials: F
authors.lastname: Vega
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D017211:Treatment Failure; D014747:Vinblastine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001761:Bleomycin; D003606:Dacarbazine; D004317:Doxorubicin; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014747:Vinblastine; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1