Improved demonstration of immunohistochemical prognostic markers for survival in follicular lymphoma cells

Abstract

Follicular lymphoma (FL) is one of the most common forms of the low-grade non-Hodgkin's lymphoma in adults, with a characteristic translocation, t(14;18)(q32;q21) that deregulates the expression of the BCL2 gene. The clinical course of FL patients is variable, whereby a subset of patients survive for long periods even without relapses, whereas the majority have frequent relapses with shorter survival. We have analyzed a series of 186 FLs, studying the correlation between clinical outcome and the tumor cell expression of a set of immunohistochemical markers, using an automated procedure for tissue microarrays to reduce the subjectivity of scoring. The results identified several markers associated with differences in overall survival (OS) in univariate analyses, such as Cyclin E, Mdm2, CD10, p21, IgD, Bcl-xL, CD30, and E2F6. Cases with a higher level of expression of Cyclin E, Mdm2, p21, IgD, Bcl-xL, CD30, and E2F6 were associated with a significantly shorter OS. On the other hand, strong CD10 expression was linked to a significantly better outcome. A Cox model was then constructed, integrating the Follicular Lymphoma International Prognostic Index (FLIPI) score and a restricted selection of three immunohistochemical markers: Cyclin E, Mdm2, and CD10 expression. A potentially useful finding is that the integrated FLIPI plus immunohistochemical model can be used to identify a subset of 26 patients (almost 20% of the total series), with a survival probability of 100% at 5 years. This not only confirms that a group of FL cases may have a very good clinical course, but also indicates that this group can be identified using this integrated clinical and immunohistochemical approach.

Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients

“…Camacho et al 41 also found worse survival in follicular lymphoma cases with higher expression of MDM2. 41 It is important to state that this study is not based on cases with uniform and standardized treatment, and includes patients treated with different protocols, reflecting the absence of any standard approach to the treatment of follicular lymphoma.…”

Diagnosis and treatment of follicular lymphoma: an update

“…The use of polymerase chain reaction (PCR) tests for detecting B cell clonality in follicular lymphoma is associated with a high rate of false negatives, due to ongoing somatic immunoglobulin variable region heavy chain (IgVH) hypermutations [22]. In addition to morphological and immunohistochemical studies, fluorescence in situ hybridisation (FISH) is the preferred method to detect the t(14;18)(q32;q21) chromosomal translocation, which is most specifically found in follicular lymphoma [23,24]. FISH analysis may have a great differential diagnostic impact, separating follicular lymphoma from reactive follicular hyperplasia and from lymphomas other than follicular lymphoma.…”

Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

“…Phenotypically, it is well known that FL display striking inter- and intratumoral heterogeneity in terms of the expression of several FL markers including immunoglobulin heavy chain (IgH), CD10, CD20 and BCL2 proteins. 1, 2, 3, 4 Genetically, copy number variation and exome sequencing studies have shown marked intratumoral clonal diversity within the FL. 5,6 Analysis of intratumoral clonal diversity within FL cases has shown that the IgH-BCL2 t(14;18) translocation is a founder event at the top of the hierarchy of FL oncogenic events, whereas other mutations such as those in CREBBP , MLL2 and TNFRS14 genes are acquired only by a fraction of the cells during tumor evolution.…”