Table 2

Clinical features and IHC score for CD8 and GrzB staining of the 80 FL cases

VariableImmunohistochemical analysis
P
Group A
Group B
High GrzB
Low GrzB
% [95% CI], N = 48% [95% CI], N = 32
Median age (range), y 57.5 (26-83) 58 (33-78) .8742* 
Sex   .121 
    Male 58 (n = 28) [43-72] 41 (n = 13) (24-59]  
    Female 42 (n = 20) [28-57] 59 (n = 19) [41-76]  
Stage   .628 
    I 4 (n = 2) [1-14] 0 (0-11]  
    II 8 (n = 4) [1-20] 9 (n = 3) [2-25]  
    III 17 (n = 8) [7-30] 25 (n = 8) [11-43]  
    IV 71 (n = 34) [56-83] 66 (n = 21) [47-81]  
FLIPI   .183 
    Low risk (0-1) 26 (n = 12) [14-40] 9 (n = 3) [2-25]  
    intermediate risk (2) 32 (n = 15) [19-47] 35 (n = 11) [19-53]  
    High (≥ 3) 42 (n = 20) [28-58] 56 (n = 18) [38-74]  
GELF   .109* 
    GELF = 0 23 (n = 11) [12-38] 9 (n = 3) [2-25]  
    GELF > 0 77 (n = 36) [62-88] 91 (n = 29) [75-98]  
BM involvement 58 (n = 28) [43-72] 63 (n = 20) [44-79] .748* 
Treatment   .592 
    R-CHOP 65 (n = 31) [49-78] 50 (n = 16) [32-68]  
    R-CVP 17 (n = 8) [7-30] 22 (n = 7) [9-40]  
    R Fludarabine-mitoxantrone 6 (n = 3) [13-17] 9 (n = 3) [2-25]  
    R-CHOP + R 10 (n = 5) [3-23] 19 (n = 6) [7-36]  
    R Fludarabine-mitoxantrone + R 2 (n = 1) [0-11] 0 (0-11)  
Immunochemistry    
    % of CD8-positive cells   .001 
        1: < 10% 0 (0-7) 12 (n = 4) [4-29]  
        2: 10%-30% 37 (n = 18) [24-53] 66 (n = 21) [47-81]  
        3: 30%-40% 44 (n = 21) [29-59] 16 (n = 5) [5-33]  
        4: > 40% 19 (n = 9) [9-33] 6 (n = 2) [8-21]  
Score GrzB    
    % of GrzB-positive cells   NC 
        1: < 10% 8 (n = 4) [2-20] 66 (n = 21) [47-81]  
        2: 10%-30% 48 (n = 23) [33-63] 34 (n = 11) [19-53]  
        3: > 30% 44 (n = 21) [29-59] 0 (0-11)  
Intensity of GrzB staining   NC 
    1: + 6 (n = 3) [1-17] 75 (n = 24) [57-89]  
    2: ++ 44 (n = 21) [29-59] 25 (n = 8) [11-43]  
    3: +++ 50 (n = 24) [35-65] 0 (0-15)  
VariableImmunohistochemical analysis
P
Group A
Group B
High GrzB
Low GrzB
% [95% CI], N = 48% [95% CI], N = 32
Median age (range), y 57.5 (26-83) 58 (33-78) .8742* 
Sex   .121 
    Male 58 (n = 28) [43-72] 41 (n = 13) (24-59]  
    Female 42 (n = 20) [28-57] 59 (n = 19) [41-76]  
Stage   .628 
    I 4 (n = 2) [1-14] 0 (0-11]  
    II 8 (n = 4) [1-20] 9 (n = 3) [2-25]  
    III 17 (n = 8) [7-30] 25 (n = 8) [11-43]  
    IV 71 (n = 34) [56-83] 66 (n = 21) [47-81]  
FLIPI   .183 
    Low risk (0-1) 26 (n = 12) [14-40] 9 (n = 3) [2-25]  
    intermediate risk (2) 32 (n = 15) [19-47] 35 (n = 11) [19-53]  
    High (≥ 3) 42 (n = 20) [28-58] 56 (n = 18) [38-74]  
GELF   .109* 
    GELF = 0 23 (n = 11) [12-38] 9 (n = 3) [2-25]  
    GELF > 0 77 (n = 36) [62-88] 91 (n = 29) [75-98]  
BM involvement 58 (n = 28) [43-72] 63 (n = 20) [44-79] .748* 
Treatment   .592 
    R-CHOP 65 (n = 31) [49-78] 50 (n = 16) [32-68]  
    R-CVP 17 (n = 8) [7-30] 22 (n = 7) [9-40]  
    R Fludarabine-mitoxantrone 6 (n = 3) [13-17] 9 (n = 3) [2-25]  
    R-CHOP + R 10 (n = 5) [3-23] 19 (n = 6) [7-36]  
    R Fludarabine-mitoxantrone + R 2 (n = 1) [0-11] 0 (0-11)  
Immunochemistry    
    % of CD8-positive cells   .001 
        1: < 10% 0 (0-7) 12 (n = 4) [4-29]  
        2: 10%-30% 37 (n = 18) [24-53] 66 (n = 21) [47-81]  
        3: 30%-40% 44 (n = 21) [29-59] 16 (n = 5) [5-33]  
        4: > 40% 19 (n = 9) [9-33] 6 (n = 2) [8-21]  
Score GrzB    
    % of GrzB-positive cells   NC 
        1: < 10% 8 (n = 4) [2-20] 66 (n = 21) [47-81]  
        2: 10%-30% 48 (n = 23) [33-63] 34 (n = 11) [19-53]  
        3: > 30% 44 (n = 21) [29-59] 0 (0-11)  
Intensity of GrzB staining   NC 
    1: + 6 (n = 3) [1-17] 75 (n = 24) [57-89]  
    2: ++ 44 (n = 21) [29-59] 25 (n = 8) [11-43]  
    3: +++ 50 (n = 24) [35-65] 0 (0-15)  

On the basis of GrzB staining patients were classified in two groups: group A (high GrzB score) and group B (low GrzB score). Group A (high GrzB score) includes patients having score 4, 5, or 6. Group B (low GrzB score) includes patients having score 1, 2, or 3. Scores were calculated by adding values corresponding to: (i) the number of GrzB+ cells (ranging from 1 to 3: with 1 = < 10% GrzB+ cells; 2 = 10%-30% GrzB+ cells; 3 = > 30% GrzB+ cells out of the CD8+ cells) and (ii) values corresponding to the intensity of GrzB staining (ranging from 1 to 3: with 1 = +; 2 = ++; 3 = +++, as shown in supplemental Figure 1).

FL indicates follicular lymphoma; IHC, immunohistochemistry; CI, confidence interval; NC, not calculated; NR, not reached; FLIPI, Follicular Lymphoma International Prognostic Index; GELF, Groupe d'Etude des Lymphomes Folliculaires; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CVP, rituximab, cyclophosphamide, vincristine, and prednisone; R-CHOP + R, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and rituximab maintenance; R-Fludarabine-mitoxantrone + R, rituximab, fludarabine, mitoxantrone, rituximab maintenance; and GrzB, granzyme B.

*

Student test.

χ2 test.

Fischer exact test.

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