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. 2012 Aug 7:5:47.
doi: 10.1186/1756-8722-5-47.

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

Wesley Greaves  1 , Lianchun Xiao, Beatriz Sanchez-Espiridion, Kranthi Kunkalla, Kunal S Dave, Cynthia S Liang, Rajesh R Singh, Anas Younes, L Jeffrey Medeiros, Francisco Vega
Affiliations

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

Wesley Greaves et al. J Hematol Oncol. .

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.

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Figures

Figure 1
Figure 1
Immunohistochemical expression of ABC proteins in positive controls and CHL tumors.A. ABCC1 is expressed by gastric glands (positive control). B. CHL with negative expression of ABCC1 by HRS cells; scattered histiocytes are weakly positive. C. CHL with HRS cells positive for cytoplasmic expression of ABCC1. D. Placenta with ABCG2 expression in trophoblastic cells (positive control). E. CHL with HRS cells negative for ABCG2; endothelial cells and scattered inflammatory cells are positive. F. CHL with HRS cells positive for cytoplasmic expression of ABCG2.
Figure 2
Figure 2
Immunohistochemical expression of ABC proteins in positive controls and call tumors. A. Canalicular staining pattern of MDR1 in liver (positive control). B. MDR1 is not expressed in the HRS cells of CHL (white arrows); endothelial cells are positive (black arrow). C. Canalicular staining pattern of ABCC2 in liver (positive control). D. HRS cells are negative for ABCC2; endothelial cells and scattered lymphocytes are positive. E. Hepatocytes show cytoplasmic expression of ABCC3 (positive control). F. HRS cells are negative for ABCC3.
Figure 3
Figure 3
ABCC1 expression was marginally associated with failure-free survival (p = 0.06).
See this image and copyright information in PMC

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