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Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with increased risk of treatment failure using standard chemotherapy protocols

Wesley Greaves1, Lianchun Xiao2, Beatriz Sanchez-Espiridion1, Kranthi Kunkalla1, Kunal S Dave1, Cynthia S Liang1, Rajesh R Singh1, Anas Younes3, L Jeffrey Medeiros1 and Francisco Vega1*

Author Affiliations

1 Department of Hematopathology, Unit 72, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

2 Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

3 Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

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Journal of Hematology & Oncology 2012, 5:47  doi:10.1186/1756-8722-5-47

Published: 7 August 2012

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.

Findings

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.

Keywords:
Classical Hodgkin lymphoma; ABCC1; ATP binding cassettes; Immunohistochemistry