TY - JOUR
T1 - Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with increased risk of treatment failure using standard chemotherapy protocols
AU - Greaves, Wesley
AU - Xiao, Lianchun
AU - Sanchez-Espiridion, Beatriz
AU - Kunkalla, Kranthi
AU - Dave, Kunal S.
AU - Liang, Cynthia S.
AU - Singh, Rajesh R.
AU - Younes, Anas
AU - Medeiros, L. Jeffrey
AU - Vega, Francisco
N1 - Funding Information:
This work was supported by funds from the K08 Physician-Scientist Award 1 K08 CA143151-01 (NIH) (to FV) SPORE Lymphoma grant UT M.D. Anderson Cancer Center Lymphoma SPORE 1P50CA136411-01A1 (to FV). A subset of patient samples were provided with assistance from the Biospecimens Core of the Lymphoma SPORE. *Dr Beatriz Sanchez-Espiridion collaborated in this work as a visiting scientist supported by the Department of Pathology, M.D. Anderson España and by Centro Nacional de Investigationes Oncologicas (CNIO), Madrid (Spain).
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - ABCC1
KW - ATP binding cassettes
KW - Classical Hodgkin lymphoma
KW - Immunohistochemistry
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U2 - 10.1186/1756-8722-5-47
DO - 10.1186/1756-8722-5-47
M3 - Article
C2 - 22871336
AN - SCOPUS:84864762788
SN - 1756-8722
VL - 5
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
M1 - 47
ER -