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Three ordinary laboratory stains, available in any hospital, were shown to sort lymphoma into the same two prognostic groups that an expensive gene-expression machine had found.
The cell-of-origin classification was a research technique: it needed fresh-frozen tissue and a microarray. Hans and colleagues asked whether routine immunohistochemistry on paraffin-embedded tissue could reproduce it. They built tissue microarray blocks from 152 cases of diffuse large B-cell lymphoma, 142 of which had already been classified by complementary DNA microarray (75 germinal-centre, 41 activated B-cell, 26 type 3), and stained for CD10, BCL6, MUM1, FOXP1, cyclin D2 and BCL2.
BCL6 (p < 0.001) and CD10 (p = 0.019) expression went with better overall survival, MUM1 (p = 0.009) and cyclin D2 (p < 0.001) with worse. Using CD10, BCL6 and MUM1, 64 cases (42 per cent) were classed germinal-centre and 88 (58 per cent) non-germinal-centre. Five-year overall survival was 76 per cent for the germinal-centre group against 34 per cent for the non-germinal-centre group (p < 0.001), similar to what the microarray gave. On multivariate analysis an International Prognostic Index of 3 to 5 and the non-germinal-centre phenotype were independent adverse predictors (p < 0.0001).
The algorithm is the reason the classification exists outside research centres. It is also the reason the classification is noisier than it looks on paper.
The practical form of cell-of-origin classification, used in pathology laboratories worldwide. When a report says germinal-centre or non-germinal-centre, this is almost always the algorithm behind it.
A failure worth reading: the drug worked where patients could tolerate the regimen it was added to, and harmed where they could not. It is the strongest argument in lymphoma for designing first-line combinations around what an older patient can finish.
The reason a pathology report on diffuse large B-cell lymphoma says germinal-centre or non-germinal-centre, and the origin of every attempt since to treat the two differently. It also made the case that microarray profiling could do something the clinical index could not, which is what pulled genomics into haematology.
One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares International Prognostic Index (IPI), BCL6, A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications, Cell of origin (GCB vs ABC) and the tag lymphoma-evidence.
Shares Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX), A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications, Cell of origin (GCB vs ABC), BCL-2 and the tag lymphoma-evidence.
Shares The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma, BCL6, Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX), A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications and the tag lymphoma-evidence.
Shares Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX), Cell of origin (GCB vs ABC), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares Cell of origin (GCB vs ABC), Biomarkers are not validated or standardised, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma and the tag lymphoma-evidence.
Shares International Prognostic Index (IPI), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Diffuse large B-cell lymphoma, Non-Hodgkin lymphoma (all types) and the tag lymphoma-evidence.