title: Detection of MYC rearrangement in high grade B cell lymphomas: correlation of MYC immunohistochemistry and FISH analysis.
abstract: The aim of this study was to analyse sensitivity, specificity and predictive values of recently available MYC immunohistochemistry (IHC) against the currently standard diagnostic method, fluorescence in situ hybridisation (FISH) analysis. MYC IHC and FISH analyses were performed on 30 cases of diffuse large B cell lymphoma (DLBCL) with 80% or more Ki-67 index, one case of DLBCL transformed from follicular lymphoma, three cases of B cell lymphoma intermediate between DLBCL and Burkitt lymphoma (IM), six cases of Burkitt lymphoma (BL) and one case of reactive lymph node. The inclusion criteria of high Ki-67 index, more than 80%, was imposed to exclude dependence of MYC positivity on Ki-67 positivity. The indices of specificity and positive predictive value (PPV) were low and varied widely with different thresholds of IHC positivity in percentage. At the threshold of 40% IHC positivity, specificity index was 0.45 and PPV was 0.37. At the threshold of 50% and 70% IHC positivity, specificity indices were 0.61 and 0.84, and PPVs were 0.45 and 0.67, respectively. Good sensitivity and negative predictive value (NPV) were maintained at all different thresholds. A heterogenous staining pattern of IHC was also noted. The heterogeneous IHC staining pattern observed warranted caution in interpretation and counting of IHC positive cells. MYC protein expression detected by IHC was more common than MYC translocation detected by FISH analysis. As a result, low specificity and PPV of MYC IHC, in relation to FISH analysis, were observed despite good sensitivity and NPV.
authors.affiliation: 1Anatomical Pathology Department, ICPMR Westmead Hospital, Westmead 2School of Medicine, University of Western Sydney, NSW, Australia.
authors.forename: Kyaw
authors.initials: K
authors.lastname: Lynnhtun
authors.forename: Jasveen
authors.initials: J
authors.lastname: Renthawa
authors.forename: Winny
authors.initials: W
authors.lastname: Varikatt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D016271:Proto-Oncogene Proteins c-myc