Clinical role of Bcl-2, Bax, or p53 overexpression in peripheral T-cell lymphomas

Abstract

Apoptosis pathways are known to be involved in the pathogenesis of peripheral T-cell lymphomas (PTCLs). As such, the current study attempted to investigate the overexpression of Bcl-2, Bax, or p53 with respect to the progression of PTCL. Paraffin-embedded specimens from 74 patients were analyzed immunohistochemically for Bcl-2, Bax, or p53 overexpression including PTCL-unspecified (n=45), extranodal natural killer cell/T-cell lymphoma (n=10), angioimmunoblastic T-cell lymphoma (n=7), anaplastic large cell lymphoma (n=7), and cutaneous T-cell lymphoma (n=5). The Bcl-2 overexpression was exhibited in 33 (45%), Bax, 17 (23%), and p53, 33 patients (45%). Bcl-2 overexpression was strongly associated with advanced stage (p=0.021) and higher international prognostic indices (IPI) (p=0.038). Bcl-2(+)/p53(+) group was found to be associated with advanced stage (p=0.008) and higher IPI (p=0.001), compared with the other groups. The independent expression of Bcl-2 or p53 was not correlated with survival. Meanwhile, when confined to Bcl-2 overexpressing groups, p53 overexpression was significantly associated with poor survival (p=0.05), as the 3-year OS rate was 82.5% for Bcl-2(+)/p53- cases, yet only 32.9% for Bcl-2(+)/p53(+) cases. Multivariate analyses for OS found the Bcl-2/p53 co-expression (p=0.004) as independent prognostic factor, together with advanced stage (p<0.001) and higher prognostic index for PTCL (p=0.008). Bcl-2 overexpression seemed to correlate with the progression of PTCL interacting with a p53-dependent pathway.

Expression of Apoptosis‐regulating Proteins Bcl‐2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma

“…Immunohistochemistry is commonly used in human lymphoid malignancies, largely because it can be performed on formalin-fixed, paraffinembedded tissue, which is readily available for routine lymphoma diagnosis in humans. 16,[18][19][20][21][22] Histopathology is considered the gold standard for characterization of lymphoma in dogs, but is more commonly reserved for cases where cytology is inconclusive. Recent studies have demonstrated that FC of LN aspirates can provide correlates with histopathology, such as determination of immunophenotype and expression of antigens associated with prognosis in subtypes of canine BCL and TCL.…”

“…In humans, a distinct translocation of the Bcl‐2 proto‐oncogene (t(14;18)) causes aberrant Bcl‐2 expression in follicular lymphoma (FL) . This and other translocations, mutations, and amplification of the Bcl‐2 gene as well as posttranslational mechanisms give rise to increased Bcl‐2 levels in diffuse large BCLs (DLBCL) and in other B‐cell tumors, and increased Bcl‐2 expression also occurs in human peripheral TCL (PTCL) . In both, Bcl‐2 overexpression, alone or in conjunction with other apoptotic proteins, was associated with worse clinical outcome .…”

“…15 This and other translocations, mutations, and amplification of the Bcl-2 gene as well as posttranslational mechanisms give rise to increased Bcl-2 levels in diffuse large BCLs (DLBCL) and in other B-cell tumors, and increased Bcl-2 expression also occurs in human peripheral TCL (PTCL). [16][17][18][19][20][21][22] In both, Bcl-2 overexpression, alone or in conjunction with other apoptotic proteins, was associated with worse clinical outcome. [18][19][20][21] Likewise, loss of function mutations in Bax, one of the key target genes of the tumor suppressor gene p53, have been identified in human lymphoblastic leukemia and lymphoma, and overexpression of Bax in human DLBCL and PTCL was associated with longer survival.…”

BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma

“…28 It has also been reported in lymphoma cells of few angioimmunoblastic T-cell lymphoma. 29 However, BCL2 overexpression in endothelial cells has not been reported so far in angioimmunoblastic T-cell lymphoma. The role of BCL2 in endothelial cells has been demonstrated by experimental studies.…”

Primary cutaneous γδ‐T‐cell lymphoma treated with low‐dose methotrexate and narrowband ultraviolet B irradiation: Report of a case with testicular involvement

“…p53, Bcl‐2 and Foxp3, which were analyzed in our case, are among the prognostic markers. Cases with double positivity of both p53 and Bcl‐2 are strongly associated with poor prognosis than cases with negative p53 9 . High expression of Foxp3, a marker for regulatory T cells, is associated with indolent course 10 .…”