Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma.

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell-like (ABC) to germinal center B-cell-like (GCB). Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes that defined clinically distinct high- and low-risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.

Improving precise counting of mitotic cells in mantle cell lymphoma using phosphohistone H3 (PHH3) antibody.

AIMS: Mantle cell lymphoma (MCL) has a highly heterogeneous clinical course ranging from indolent, to aggressive and rapidly progressive disease. Proliferation is a strong predictor for disease outcome. In routine clinical practice, Ki-67 expression is used as a measure of proliferation. However, several studies have documented a high degree of inter-laboratory and inter-observer variation with Ki-67 immunohistochemistry. Phosphorylation of histone H3 occurs specifically during mitosis and hence serves as a specific marker for cells in mitosis. METHODS AND RESULTS: We investigated phosphohistone H3 (PHH3) immunohistochemistry as a proliferation maker in 28 tissue biopsies of MCL and compared the PHH3 results (as evaluated by direct microscopic visualisation and image analysis-aided scoring) with morphological subtyping, mitotic counts and Ki-67 index. We found PHH3-mitotic count was about sixfold higher than H&E-mitotic count (mitoses in 10 high power fields). Furthermore, PHH3-mitotic count in aggressive morphological variants of MCL was significantly higher than in usual MCL. The PHH3-mitotic count showed a strong linear correlation with PHH3-mitotic index (percentage positive cells). CONCLUSIONS: We found PHH3 immunohistochemistry, a reliable mitosis-specific marker, in MCL. Performing precise counts and evaluating precise proliferation indices is easier with PHH3 immunohistochemistry. This contrasts with the conventional estimation of Ki-67 percentages by 'eye-balling'.

Does muscle-sparing thoracotomy as opposed to posterolateral thoracotomy result in better recovery?

A best evidence topic was written according to a structured protocol. The question addressed was whether muscle-sparing thoracotomy (MST), as opposed to posterolateral thoracotomy (PLT), results in better recovery. A total of 108 papers were found using the reported searches of which eight represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. A recent large prospective, randomized, double-blinded, controlled study demonstrated a shorter length of stay in patients undergoing MST. It failed to demonstrate any significant difference in pain reported or pulmonary function. A separate prospective randomized controlled trial focussed on pain, pulmonary function, late shoulder range of motion and late muscle strength. It failed to show any significant difference in these domains between PLT and MST. While the mean 'opening time' is greater when performing a MST, this is negated by a shorter mean 'closing time' when compared with PLT. Overall, the evidence suggests that MST results in greater early (1 week) preservation of skeletal muscle strength and range of motion over PLT. This difference has disappeared at 1 month. There is little evidence to suggest a difference in pulmonary function or pain dependent on the thoracotomy type. Moreover, analgesic consumption is similar. However, there is an inverse relationship between the incision length and the post-thoracotomy syndrome.