Decreased BIM expression in BCL2-negative follicular lymphoma: a potential mechanism for resistance to apoptosis


Hum Pathol. 2020 Oct 8:S0046-8177(20)30197-0. doi: 10.1016/j.humpath.2020.09.016. Online ahead of print.


Follicular lymphoma (FL) is characterized by the t(14;18)(q32;q21), leading to overexpression of the anti-apoptotic molecule BCL2; however, a subset of FLs lack BCL2 rearrangement and BCL2 expression by IHC. In this study we evaluated expression of anti-apoptotic (MCL1 and BCL-XL) and pro-apoptotic proteins (BIM) by IHC in both BCL2(-) and BCL2(+) FLs. FLs diagnosed between 2009-2019 were reviewed to identify BCL2(-) cases by IHC (assessed by clone 124). IHC stains for BCL2 (EP36), MCL1, BIM,

BCL-XL, and Ki-67 were performed on tissue microarrays or whole slides. BCL2 (EP36) was interpreted as positive (≥10%) or negative (<10%). Ki-67 was interpreted on tumor cells in 10% increments. The remaining stains were scored on tumor cells in 10% increments and intensity was interpreted as weak, moderate, or strong to derive an H-score. 24 BCL2(-) FLs were initially identified, but on further testing with BCL2(EP36) IHC, 5/24 were reclassified as BCL2(+) leaving 19 BCL2(-) FLs. 33 BCL2(+) FLs were selected with sufficient tissue for additional IHC. There was no significant difference in expression of anti-apoptotic BCL-XL or MCL1 between BCL2(-) and BCL2(+) FLs (p= 0.75 and 0.28, respectively). However, pro-apoptotic BIM expression was significantly lower in BCL2(-) FLs compared to BCL2(+) FLs (p=0.002). In our study, 21% of putative BCL2(-) FLs were BCL2(+) when tested with alternative clones, supporting the practice of having more than one BCL2 clone in IHC labs. Decreased BIM in BCL2(-) FLs could have an overall anti-apoptotic effect and represent an alternate mechanism for cell survival in BCL2(-) FLs.