Tissue microarray is inappropriate for analysis of BCL6 expression in diffuse large B-cell lymphoma.
OBJECTIVE
In this study, our aim was to investigate how different immunohistochemical techniques may influence the result of BCL6 positivity and categorization in germinal center (GC) and non-GC derived diffuse large B-cell lymphoma (DLBCL), as it has been proposed that classification of DLBCL according to cell-of-origin by immunohistochemistry may be performed as a routine procedure in the diagnostic work-up. However, a number of technical issues need to be solved before introducing this as a standard technique.


METHODS
Tumor specimens from 122 patients with de novo stage II-IV disease, adequately treated with anthracycline-containing chemotherapy regimens were collected. Immunohistochemical expression of BCL6, CD10, and MUM-1/IRF4 was examined using a tissue microarray (TMA) technique. BCL6 and CD10 were also evaluated on whole tissue sections.


RESULTS
Due to profound tissue heterogeneity, BCL6 showed a wide range of positivity, with a high number of false negative results by TMA (25% positive), compared to 53% on whole tissue sections (WTS). CD10 was more homogeneously expressed, and TMA results corresponded better to WTS. Consequently, the results from categorization into GC and non-GC DLBCL differed considerably by use of the two methods, and resulted in very different outcome in terms of overall survival.


CONCLUSIONS
Immunohistochemical GC-status determined on TMA is not reliable enough to be used for individual treatment decisions in DLBCL, mostly due to difficulties in interpreting BCL6 status.
Linderoth
Johan
J
Department of Oncology, Lund University Hospital, Lund, Sweden. johan.linderoth@med.lu.se
Ehinger
Mats
M
Akerman
Måns
M
Cavallin-Ståhl
Eva
E
Enblad
Gunilla
G
Erlanson
Martin
M
Jerkeman
Mats
M
D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015260:Neprilysin / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism*; D046888:Tissue Array Analysis
D051560:Proto-Oncogene Proteins c-bcl-6; D015260:Neprilysin