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Abstract
Background
Biomarkers of lymphomas identified by immunostaining of lymphoma tissues were recently found to have a prognostic value for diffuse large B-cell lymphoma (DLBL). Thus, it seems likely that the prognostic prediction of lymphomas might be improved by incorporating biological markers into well known prognostic systems.
Methods
To determine the clinical significance of the biological markers expressed in DLBL, 26 patients, with de novo DLBL, were retrospectively studied at the Chungnam National University Hospital. Archival specimens from the patients were stained with antibodies for the bcl-2, bcl-6, Ki-67, CD 10, IRF-4, Granzyme-B, MHC-II and p16 antigens. Two immunophenotypic patterns of DLBL were identified by the pattern of differentiation; the germinal center (GC, CD10±/Bcl-6+/IRF-4-)-like subgroup and the post germinal center (pGC, CD10±/bcl-6±/IRF4+)-like subgroup.
Results
The median age of the subjects was 56 years, ranging form 37 to 69. After a median follow up duration of 48 months, the median survival time was 44 month, ranging from 1～100 months. The five-year overall survival rate Using the Kaplan-Meier method was 32%. The only biomarker affecting the survival was bcl-2 (P=0.009). The survival of the GC-like subgroup was superior to that of the pGC-like subgroup, but without statistical significance (P=0.064). Among 18 patients with IPI scores 0～ 2, those expressing bcl-2 (P=0.002) and the pGC-like subgroup had a worse prognosis compared to the GC-like subgroup (P=0.049).
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Fig. 4.
Kaplan Meier survival curve according to GC-like subgroup and pGC-like subgroup (P=0.064). The undifferentiated subgroup was excluded.
Fig. 6.
Kaplan Meier survival curve according to GC-like subgroup or pGC-like subgroup in patients with IPI score 0～ 2 (P=0.049). The undifferentiated subgroup was excluded.
Table 1.
The clinical characteristics and factors affecting survival in DLBL patients (No.=26)
Table 2.
The biologic characteristics and markers affecting survival in DLBL patients (No.=26)
| Characteristics | No. of patients (%) | Median survival (month) | P value |
|---|---|---|---|
| Bcl-2 | 0.009 | ||
| Positive | 17 (65.4) | 20 | |
| Negative | 9 (34.6) | Not reached | |
| Bcl-6 | 0.425 | ||
| Positive | 20 (76.9) | 24 | |
| Negative | 6 (23.1) | 18 | |
| Ki-67 | 0.859 | ||
| ＜60 | 9 (34.6) | 44 | |
| ≥60 | 17 (65.4) | 20 | |
| CD10 | 0.552 | ||
| Positive | 5 (19.2) | Not reached | |
| Negative | 21 (80.8) | 24 | |
| IRF-4 | 0.184 | ||
| Positive | 8 (30.8) | 20 | |
| Negative | 18 (69.2) | 51 | |
| Granzyme-B | 0.533 | ||
| 1+ | 17 (65.4) | 50 | |
| 2+ | 5 (19.2) | 18 | |
| 3+ | 4 (15.4) | 11 | |
| MHC-II | 0.447 | ||
| Positive | 23 (88.5) | 44 | |
| Negative | 3 (11.5) | 10 | |
| p16 | 0.372 | ||
| Positive | 4 (15.4) | 44 | |
| Negative | 22 (84.6) | 20 | |
| Subgroup | 0.064∗ | ||
| GC group | 14 (53.8) | 51 | |
| pGC group | 7 (27.0) | 20 | |
| Undifferentiated | 5 (19.2) |
Table 3.
The biologic characteristics and markers affecting survival in DLBL patients with IPI score 0～2 (No.=18)
| Characteristics | No. of patients (%) | Median survival (month) | P value |
|---|---|---|---|
| Bcl-2 | 0.002 | ||
| Positive | 11 (61.1) | 44 | |
| Negative | 7 (38.9) | Not reached | |
| Bcl-6 | 0.370 | ||
| Positive | 15 (83.3) | 51 | |
| Negative | 3 (16.7) | Not reached | |
| Ki-67 | 0.352 | ||
| ＜60 | 7 (38.9) | 51 | |
| ≥60 | 11 (61.1) | Not reached | |
| CD 10 | 0.169 | ||
| Positive | 3 (16.7) | Not reached | |
| Negative | 15 (83.3) | 51 | |
| IRF-4 | 0.101 | ||
| Positive | 5 (27.8) | 44 | |
| Negative | 13 (72.2) | Not reached | |
| Granzyme B | 0.381 | ||
| 1+ | 14 (77.8) | 51 | |
| 2+ | 2 (11.1) | 15 | |
| 3+ | 2 (11.1) | Not reached | |
| MHC-II | 0.418 | ||
| Positive | 17 (94.4) | 57 | |
| Negative | 1 (5.6) | Not reached | |
| p16 | 0.448 | ||
| Positive | 3 (16.7) | Not reached | |
| Negative | 15 (83.3) | 57 | |
| Subgroup∗ | 0.049 | ||
| GC | 11 (61.1) | Not reached | |
| pGC | 4 (22.2) | 24 |
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