Southern blot analysis of lymphoproliferative disorders: use and limitations in routine surgical pathology.
Antigen receptor gene rearrangement studies are a sensitive means of determining lineage and clonality in lymphoproliferative disorders (LPDs) which remain difficult to classify after assessment of morphology and immunohistochemistry (IHC). This study investigates the utility of genotyping LPDs in a surgical pathology laboratory servicing a large teaching hospital. Ninety-eight specimens with detailed frozen (FS) and/or paraffin section IHC were studied, including 65 B-cell lymphomas, 14 T-cell lymphomas, 2 biopsies of T-zone dysplasia, one unclassifiable lymphoma, 8 Hodgkin's disease (HD) and 8 reactive nodes. Southern blotting (SB) was performed on tumor and control DNA cleaved with restriction enzymes EcoR1, Hind III and BamH1, using radiolabelled probes for the immunoglobulin heavy chain joining region, constant regions of kappa and lambda light chains, and the constant region of the T-cell receptor beta chain. All reactive nodes and those harbouring HD and DNA in the germline configuration, apart from JH rearrangement in one case each of HD and florid reactive hyperplasia. Of the non-Hodgkin's lymphomas (NHL), 17% did not reveal clonal rearrangements (11% B-NHL; 44% T-NHL). Most of the negative results could be explained by sampling error in partially involved nodes, highly polymorphous infiltrates where the neoplastic population may have been below the 1% threshold detectable by SB, and instances of anaplastic large cell lymphoma. After accounting for these cases, a 5% negative rate of genoclonality remained (3% B-NHL; 13% T-NHL). In the majority of NHL (95%), the diagnosis could be established on the basis of morphology and/or IHC alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Spagnolo
D V
DV
Department of Histopathology and Laboratory of Molecular Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
Taylor
J
J
Carrello
S
S
Saueracker
E
E
Kay
P H
PH
D015139:Blotting, Southern; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D010340:Pathology, Surgical / Q000379:methods*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
D016693:Receptors, Antigen, T-Cell, alpha-beta