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There is increasing evidence that bcl6 and CD10 expression may be related to apoptosis and cell cycle progression. Therefore, 79 cases of de novo diffuse large B-cell lymphomas were studied for the expression of bcl6 and CD10 proteins in relation to 1) the apoptotic index; 2) the proliferationassociated proteins Ki67, cyclin A, and cyclin B1; and 3) the expression of the bcl2, p53, Rb, p16, and p27 proteins. Expression of bcl6, CD10, and bcl2 proteins was found in 54/79 (68%), 28/79 (35%), and 47/74 (63%) cases, respectively. The bcl6/CD10 patterns were as follows: bcl6؉/CD10؉ (26 cases, 32%), bcl6؉/CD10-(28 cases, 33%), bcl6؊/CD10؊ (23 cases, 31%), and bcl6؊/CD10؉ (2 cases, 4%). Significant positive correlations were found between bcl6/Ki67 (r ‫؍‬ .328, P ‫؍‬ .003), bcl6/cyclin A (r ‫؍‬ .265, P ‫؍‬ .018), bcl6/apoptotic index (r ‫؍‬ .327, P ‫؍‬ .010), CD10/Ki67 (r ‫؍‬ .296, P ‫؍‬ .008), and CD10/ apoptotic index (r ‫؍‬ .397, P ‫؍‬ .001). In addition, high expression of bcl6 showed significant correlation with negative (null/low) bcl2 expression ( 2 test, P ‫؍‬ .002). The above findings indicate that increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas. The association between increased bcl6 expression and enhanced apoptosis might be due, at least in part, to the null/low bcl2 expression because previous in vitro data showed that bcl6 overexpression induces apoptosis accompanied by bcl2 and bcl-xl downregulation. Moreover, significant correlation was found between increased apoptotic index and the bcl6؉/CD10؉ pattern (t test: P ‫؍‬ .014, MannWhitney test: P ‫؍‬ .046). This finding and the positive correlation of the apoptotic index with bcl6 and CD10 expression may be related to previous results showing that the expression of these proteins has favorable effects on the clinical outcome of diffuse large B-cell lymphomas.

Transcription factors play an essential role in regulating both cell proliferation and programmed cell death. Proliferation and apoptosis-related transcription factor immunoexpression patterns were concomitantly investigated in tissue sections of normal thyroid, goiters, follicular adenomas and well-differentiated papillary and follicular carcinomas using antibodies against prothymosin alpha, E2F-1, p53, Bcl2, and Bax proteins. Proliferation and apoptotic indices were determined by Ki-67 immunoreactivity and the terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling technique, respectively. Prothymosin alpha and E2F-1 immunoexpression levels were found to be significantly elevated in well-differentiated carcinomas compared to adenomas, goiters and normal tissues (P < 0.05). Both proteins were directly correlated with the proliferation index (P < 0.05). E2F-1 was additionally correlated with the apoptotic index (P < 0.05). The majority of cases were negative for p53 staining. Positive Bcl2 immunostaining was detected in all thyroid histotypes. None of the normal tissues showed Bax immunoreactivity, while positive accumulation differed significantly between hyperplastic and neoplastic histotypes. Direct correlations were observed between prothymosin alpha and Bcl2 as well as between E2F-1 and Bax immunoexpression (P < 0.05). These data demonstrate that prothymosin alpha and E2F-1 are strongly involved in the proliferation processes of thyroid neoplasias. Furthermore, prothymosin alpha may promote cell survival through the Bcl2 anti-apoptotic pathway, while E2F-1-induced apoptosis via p53-independent pathways may be associated with transcriptional activation of bax pro-apoptotic gene.

The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10+/-/MUM1-/CD138-: 29 cases and bcl6-/CD10+/MUM1-/CD138-: two cases) and the nongerminal center B-cell-like profile (bcl6+/-/CD10-/MUM1+/CD138-); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=-0.536, P<0.001 and r=-0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=-0.276, P=0.014) and bid (r=-0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.

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