Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients

被引:35
作者
Culpin, Rachel E. [1 ]
Sieniawski, Michal [1 ]
Angus, Brian [2 ]
Menon, Geetha K. [2 ]
Proctor, Stephen J. [1 ]
Milne, Paul [1 ]
McCabe, Kate [1 ]
Mainou-Fowler, Tryfonia [1 ]
机构
[1] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
关键词
diffuse large B cell lymphoma; immunohistochemistry; N-HL; predictive algorithms; prognosis; survival; NON-HODGKINS-LYMPHOMA; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; GERMINAL CENTER PHENOTYPE; R-CHOP; PROTEIN EXPRESSION; TISSUE MICROARRAY; BIOMARKER CONSORTIUM; RISK STRATIFICATION; BCL-2; EXPRESSION; STRONG PREDICTOR;
D O I
10.1111/his.12223
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
AimsTo reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients. Methods and resultsThe prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (80%) predicted shorter overall survival (OS; P=0.033, P=0.010 and P=0.008, respectively). High Bcl-2 (80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival (PFS; P=0.001, P=0.048, P=0.045 and P=0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS (P=0.022, P=0.037 and P=0.011) and PFS (P=0.021, P=0.020 and P=0.004). The Choi, Choi* and Tally were associated with PFS (P=0.049, P=0.009 and P=0.023). In multivariate analysis, the International Prognostic Index (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P<0.001 and PFS; HR: 2.91, P<0.001). ConclusionsResults highlight the controversy surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized.
引用
收藏
页码:788 / 801
页数:14
相关论文
共 52 条
[1]  
Alas S, 2001, CLIN CANCER RES, V7, P709
[2]   Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].
Alizadeh, AA ;
Eisen, MB ;
Davis, RE ;
Ma, C ;
Lossos, IS ;
Rosenwald, A ;
Boldrick, JG ;
Sabet, H ;
Tran, T ;
Yu, X ;
Powell, JI ;
Yang, LM ;
Marti, GE ;
Moore, T ;
Hudson, J ;
Lu, LS ;
Lewis, DB ;
Tibshirani, R ;
Sherlock, G ;
Chan, WC ;
Greiner, TC ;
Weisenburger, DD ;
Armitage, JO ;
Warnke, R ;
Levy, R ;
Wilson, W ;
Grever, MR ;
Byrd, JC ;
Botstein, D ;
Brown, PO ;
Staudt, LM .
NATURE, 2000, 403 (6769) :503-511
[3]  
[Anonymous], 1993, N ENGL J MED, V329, P987
[4]  
Banham AH, 2005, CLIN CANCER RES, V11, P1065
[5]   Rearrangement of MYC Is Associated With Poor Prognosis in Patients With Diffuse Large B-Cell Lymphoma Treated in the Era of Rituximab [J].
Barrans, Sharon ;
Crouch, Simon ;
Smith, Alex ;
Turner, Kathryn ;
Owen, Roger ;
Patmore, Russell ;
Roman, Eve ;
Jack, Andrew .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (20) :3360-3365
[6]   Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome [J].
Barrans, SL ;
Fenton, JAL ;
Banham, A ;
Owen, RG ;
Jack, AS .
BLOOD, 2004, 104 (09) :2933-2935
[7]  
Barrans SL, 2003, CLIN CANCER RES, V9, P2133
[8]   Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma [J].
Barrans, SL ;
Carter, I ;
Owen, RG ;
Davies, FE ;
Patmore, RD ;
Haynes, AP ;
Morgan, GJ ;
Jack, AS .
BLOOD, 2002, 99 (04) :1136-1143
[9]   Evaluation of intra- and interobserver agreement and its clinical significance for scoring bcl-2 immunohistochemical expression in diffuse large B-cell lymphoma [J].
Borlot, Vinicius Freitas ;
Biasoli, Irene ;
Schaffel, Rony ;
Azambuja, Denize ;
Milito, Cristiane ;
Luiz, Ronir Raggio ;
Scheliga, Adriana ;
Spector, Nelson ;
Morais, Jose Carlos .
PATHOLOGY INTERNATIONAL, 2008, 58 (09) :596-600
[10]  
CARBONE PP, 1971, CANCER RES, V31, P1860