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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number47
JournalJournal of Hematology and Oncology
Volume5
DOIs
StatePublished - Aug 9 2012
Externally publishedYes

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Treatment Failure
Hodgkin Disease
Drug Therapy
Reed-Sternberg Cells
ATP-Binding Cassette Transporters
Doxorubicin
Neoplasms
Dacarbazine
Survival
Vinblastine
Bleomycin
Multiple Drug Resistance
Drug Resistance
Albumins
Hemoglobins
Multivariate Analysis
Immunohistochemistry
Cell Line
Therapeutics

Keywords

  • ABCC1
  • ATP binding cassettes
  • Classical Hodgkin lymphoma
  • Immunohistochemistry

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Molecular Biology

Cite this

Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with increased risk of treatment failure using standard chemotherapy protocols. / Greaves, Wesley; Xiao, Lianchun; Sanchez-Espiridion, Beatriz; Kunkalla, Kranthi; Dave, Kunal S.; Liang, Cynthia S.; Singh, Rajesh R.; Younes, Anas; Medeiros, L. Jeffrey; Vega, Francisco.

In: Journal of Hematology and Oncology, Vol. 5, 47, 09.08.2012.

Research output: Contribution to journalArticle

Greaves, Wesley ; Xiao, Lianchun ; Sanchez-Espiridion, Beatriz ; Kunkalla, Kranthi ; Dave, Kunal S. ; Liang, Cynthia S. ; Singh, Rajesh R. ; Younes, Anas ; Medeiros, L. Jeffrey ; Vega, Francisco. / Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with increased risk of treatment failure using standard chemotherapy protocols. In: Journal of Hematology and Oncology. 2012 ; Vol. 5.
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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{\circledR}), 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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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

PY - 2012/8/9

Y1 - 2012/8/9

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.

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KW - ATP binding cassettes

KW - Classical Hodgkin lymphoma

KW - Immunohistochemistry

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