Detection of ABCC1 expression in classical Hodgkin
lymphoma is associated with increased risk of
treatment failure using standard chemotherapy
protocols
The mechanisms responsible for chemoresistance in patients with refractory classicalHodgkin lymphoma (CHL) are unknown. ATP-binding cassette (ABC) transporters confermultidrug resistance in various cancers and ABCC1 overexpression has been shown tocontribute to drug resistance in the CHL cell line, KMH2.FindingsWe analyzed for expression of five ABC transporters ABCB1, ABCC1, ABCC2, ABCC3and ABCG2 using immunohistochemistry in 103 pre-treatment tumor specimens obtainedfrom patients with CHL.
All patients received first-line standard chemotherapy withdoxorubicin (Adriamycin(R)), bleomycin, vinblastine, and dacarbazine (ABVD) or equivalentregimens. ABCC1 was expressed in Hodgkin and Reed-Sternberg (HRS) cells in 16 of 82cases (19.5%) and ABCG2 was expressed by HRS cells in 25 of 77 cases (32.5%),respectively.
All tumors were negative for ABCB1, ABCC2 and ABCC3. ABCC1 expressionwas associated with refractory disease (p = 0.01) and was marginally associated with poorerfailure-free survival (p = 0.06).
Multivariate analysis after adjusting for hemoglobin andalbumin levels and age showed that patients with CHL with HRS cells positive for ABCC1had 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 treatmentfailure and is marginally associated with poorer failure-free survival using standard frontlinechemotherapy regimens.
Author: Wesley GreavesLianchun XiaoBeatriz Sanchez-EspiridionKranthi KunkallaKunal S DaveCynthia S LiangRajesh R SinghAnas YounesL Jeffrey MedeirosFrancisco Vega Credits/Source: Journal of Hematology &Oncology 2012, 5:47
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