TY - JOUR
T1 - Apoptosis stimulating protein of p53 (ASPP2) expression differs in diffuse large B-cel and follicular center lymphoma
T2 - Correlation with clinical outcome
AU - Lossos, Izidore S.
AU - Natkunam, Yasodha
AU - Levy, Ronald
AU - Lopez, Charles D.
N1 - Funding Information:
We thank Yi-Ching Hsieh of the Oregon Cancer Center Biostatistics Resource Facility for help with the statistical analysis. Supported by USPHS-NIH grants CA33399 and CA34233 to RL, and CA85773 to CL. RL is an American Cancer Society Clinical Research Professor.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - ASPP2 interacts with the tumor suppressor protein p53, promotes damage-induced apoptosis, and can specifically stimulate p53 apoptotic function. Thus, ASPP2 may function as a tumor suppressor and/or play a role in the cellular response to cytotoxic injury. To explore the role of ASPP2 in human cancer, we determined ASPP2 expression in two lymphoma subtypes with differing clinical outcomes: diffuse large B-cell lymphoma (DLBCL) and follicular center lymphoma (FCL). A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to detect ASPP2 mRNA. Sixty-one DLBCL and twenty-three FCL cases were analyzed and normalized ASPP2 levels were expressed relative to an mRNA standard. We found that ASPP2 mean expression strongly correlated with lymphoma subtype: DLBCL = 11.74 and FCL = 4.99 (p = 0.029, unpaired 2-tailed t-test). Importantly, ASPP2 expression was variable in DLBCL but not FCL (DLBCL-range, 0.04-94.6; FCL-range, 1.2-15.0). In these DLBCL cases, serum lactate dehydrogenase (LDH) was an independent predictor of survival with median survival in the high LDH group of 24 months and median survival not achieved in the normal-low LDH group (p = 0.014, Log-Rank Test). Mean ASPP2 levels trended toward an inverse correlation with LDH levels: High LDH, ASPP2 = 6.2; Normal-low LDH, ASPP2 = 18.2 (p = 0.074, unpaired 2-tailed t-test). In the DLBCL cases with ASPP2 levels > 7.8, only 10% (1/10) had a high LDH, in contrast to cases with ASPP2 levels < 7.8 in which 59% (26/44) had a high LDH (p = 0.011, Fisher Exact Test). Thus, low ASPP2 mRNA levels may correlate with poor clinical outcome in lymphoma which is consistent with the hypothesis that ASPP2 may play a role in tumor formation and/or sensitivity to cytotoxic agents. Larger studies as well as analysis of different tumor types are warranted.
AB - ASPP2 interacts with the tumor suppressor protein p53, promotes damage-induced apoptosis, and can specifically stimulate p53 apoptotic function. Thus, ASPP2 may function as a tumor suppressor and/or play a role in the cellular response to cytotoxic injury. To explore the role of ASPP2 in human cancer, we determined ASPP2 expression in two lymphoma subtypes with differing clinical outcomes: diffuse large B-cell lymphoma (DLBCL) and follicular center lymphoma (FCL). A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to detect ASPP2 mRNA. Sixty-one DLBCL and twenty-three FCL cases were analyzed and normalized ASPP2 levels were expressed relative to an mRNA standard. We found that ASPP2 mean expression strongly correlated with lymphoma subtype: DLBCL = 11.74 and FCL = 4.99 (p = 0.029, unpaired 2-tailed t-test). Importantly, ASPP2 expression was variable in DLBCL but not FCL (DLBCL-range, 0.04-94.6; FCL-range, 1.2-15.0). In these DLBCL cases, serum lactate dehydrogenase (LDH) was an independent predictor of survival with median survival in the high LDH group of 24 months and median survival not achieved in the normal-low LDH group (p = 0.014, Log-Rank Test). Mean ASPP2 levels trended toward an inverse correlation with LDH levels: High LDH, ASPP2 = 6.2; Normal-low LDH, ASPP2 = 18.2 (p = 0.074, unpaired 2-tailed t-test). In the DLBCL cases with ASPP2 levels > 7.8, only 10% (1/10) had a high LDH, in contrast to cases with ASPP2 levels < 7.8 in which 59% (26/44) had a high LDH (p = 0.011, Fisher Exact Test). Thus, low ASPP2 mRNA levels may correlate with poor clinical outcome in lymphoma which is consistent with the hypothesis that ASPP2 may play a role in tumor formation and/or sensitivity to cytotoxic agents. Larger studies as well as analysis of different tumor types are warranted.
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U2 - 10.1080/1042819021000040017
DO - 10.1080/1042819021000040017
M3 - Article
C2 - 12613517
AN - SCOPUS:1842854235
SN - 1042-8194
VL - 43
SP - 2309
EP - 2317
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 12
ER -