Table 1. Frequencies of MYC, BCL2 and BCL6 gene translocations and protein overexpression, and multivariate survival analysis.
| Overall | GCB | ABC | GCB vs ABC | OS | PFS | |||
|---|---|---|---|---|---|---|---|---|
| n/n (%) | n/n (%) | n/n (%) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |
| MYC translocation | 71/600 (11.8%) | 51/314 (16.2%) | 20/284 (7.0%) | .0005 | 1.36 (0.83-2.23) | .22 | 1.26 (0.79-2.01) | .34 |
| BCL2 translocation | 94/690 (13.6%) | 85/360 (23.6%) | 9/328 (2.7%) | <.0001 | 1.39 (0.86-2.24) | .17 | 1.34 (0.86-2.09) | .20 |
| BCL6 translocation | 145/628 (23.1%) | 59/338 (17.5%) | 86/286 (30.1%) | .0002 | 1.06 (0.70-1.61) | .77 | 1.13 (0.77-1.66) | .53 |
| MYC+ expression | 249/825 (30.2%) | 121/430 (28.1%) | 127/390 (32.6%) | .17 | 1.89 (1.26-2.84) | .002 | 1.85 (1.26-2.71) | .002 |
| BCL2+ expression | 439/849 (51.7%) | 194/439 (44.2%) | 245/406 (60.3%) | <.0001 | 1.67 (1.14-2.46) | .009 | 1.70 (1.19-2.42) | .004 |
| BCL6+ expression | 555/887 (62.6%) | 350/462 (75.8%) | 204/424 (48.1%) | <.0001 | 0.67 (0.45-1.00) | .048 | 0.47 (0.40-0.89) | .016 |
| MYC+/BCL2+ double-hit | 20/710 (2.8%) | 19/359 (5.3%) | 1/349 (0.3%) | <.0001 | 3.38 (1.75-6.52) | <.0001 | 3.04 (1.63-5.67) | <.0001 |
| MYC+/BCL6+ concurrent translocation | 14/683 (2.0%) | 9/356 (2.5%) | 5/323 (1.5%) | .37 | 0.67 (0.23-1.97) | .47 | 0.85 (0.33-2.21) | .74 |
| BCL2+/BCL6+ concurrent translocation | 21/718 (2.9%) | 18/371 (4.9%) | 3/341 (0.9%) | .0045 | 0.47 (0.16-1.39) | .14 | 0.52 (0.20-1.33) | .17 |
| MYC+/BCL2+ double-positive | 146/831 (17.6%) | 62/434 (14.3%) | 84/390 (21.5%) | .0079 | 2.54 (1.65-3.94) | <.0001 | 2.92 (1.91-4.47) | <.0001 |
| MYC+/BCL6+ co-expression | 178/821 (21.7%) | 97/434 (22.4%) | 81/413 (19.6%) | .35 | 1.02 (0.65-1.58) | .94 | 0.85 (0.56-1.30) | .46 |
| BCL2+/BCL6+ co-expression | 282/845 (33.4%) | 151/443 (34.1%) | 131/415 (31.6%) | .47 | 1.01 (0.68-1.49) | .97 | 0.90 (0.62-1.30) | .58 |
| MYC+/BCL2+/BCL6− | 43/871 (4.9%) | 13/460 (2.8%) | 30/403 (7.4%) | .0019 | 1.60 (1.01-2.54) | .046 | 2.16 (1.39-3.34) | .001 |
| MYC+/BCL6+/BCL2− | 75/850 (8.8%) | 49/434 (11.3%) | 26/412 (6.3%) | .011 | 0.87 (0.54-1.40) | .56 | 0.86 (0.58-1.34) | .51 |
| MYC+/BCL2+/BCL6+ | 101/829 (12.2%) | 47/432 (10.9%) | 54/390 (13.8%) | .20 | 2.57 (1.86-3.56) | <.0001 | 2.41 (1.77-3.28) | <.0001 |
| (triple-positive) | ||||||||
Abbreviations: OS, overall survival; PFS, progression-free survival; HR, hazard ratio; CI, confidence interval.
Note: (1) Not all the patients had experiment results available for all three genes (MYC/BCL2/BCL6) or protein mostly due to tissue exhaustion. Total patient numbers for particular biomarkers are listed. For defined combination biomarkers (double-hit/concurrent translocation or double positive/co-expression), total case numbers are more than those for single markers because some cases had only one gene/protein (as a component of the defined biomarker combinations) data available and the results were negative. For example, cases known to have no MYC translocation but without BCL2 translocation status known are included as non MYC+/BCL2+ double-hit cases during frequency calculation.
(2) For multivariate analyses, four Cox models including different prognostic factors were used. The first model included 4 clinical parameters (International Prognostic Index, gender, B-symptoms, and tumor size), MYC, BCL2, and BCL6 translocation status, and MYC, BCL2, and BCL6 protein expression levels as variables (totally 10 factors) and the results are as shown in the top six rows. The second model included clinical parameters, and status for MYC+/BCL2+, MYC+/BCL6+, BCL2+/BCL6+, MYC+/BCL2+, MYC+/BCL6+ and BCL2+/BCL6+ (totally 10 factors) and the results are shown in the 7th-12th rows. The third models included clinical parameters, and status for “MYC+/BCL2+/BCL6− and MYC+/BCL6+/BCL2− (totally 6 factors) and the results are shown in the 13-14 rows. The fourth model included clinical parameters and MYC+/BCL2+/BCL6+ as a factor and the results are shown in the last row.