Several transcription factors predominantly used for B-cell lineage identification are also expressed in a small percentage of T cells within germinal centers and interfollicular areas. The aim of the study was to evaluate the expression of Mum-1, Oct-2 and Bcl-6 in systemic anaplastic large cell lymphoma.
Methods
Thirty cases of anaplastic large cell lymphoma were retrieved from our archives and tissue microarray constructed. Immunohistochemistry was carried out using an avidin-biotin peroxidase complex method.
Results
A predominance of nuclear staining was observed for all transcription factors. Mum-1 was positive in all but one case (96.7%). Half of the cases displayed Oct-2 expression (15/30 cases). A considerable number of cases also had Bcl-6 expression (9/30). Bcl-6 staining was noted to be more common in ALK positive cases.
Conclusion
Our findings emphasize that these markers are not restricted to B-cell lineage and that extensive expression can be observed in anaplastic large cell lymphoma of T/null cell phenotype.
PonzoniM., ArrigoniG., DoglioniC.: New transcription factors in diagnostic hematopathology.Adv Anat Pathol, 14: 25–35, 2007.
2.
FaliniB., FizzottiM., PucciariniA., BigernaB., MarafiotiT., GambacortaM., PaciniR., AlunniC., Natali-TanciL., UgoliniB., SebastianiC., CattorettiG., PileriS., Dalla-FaveraR., SteinH.: A monoclonal antibody (MUM1p) detects expression of the MUM 1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells.Blood, 95: 2084–2092, 2000.
3.
NatkunamY., WarnkeR.A., MontgomeryK., FaliniB., van de RijnM.: Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry.Mod Pathol, 14: 686–694, 2001.
4.
KangS.M., TsangW., DollS., ScherleP., KoH.S., TranA.C., LenardoM.J., StaudtL.M.: Induction of the POU domain transcription factor Oct-2 during T-cell activation by cognate antigen.Mol Cell Biol, 12: 3149–3154, 1992.
5.
TsuboiK., IidaS., InagakiH., KatoM., HayamiY., HanamuraI., MiuraK., HaradaS., KikuchiM., KomatsuH., BannoS., WakitaA., NakamuraS., EimotoT., UedaR.: MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies.Leukemia, 14: 449–456, 2000.
6.
SaezA.I., ArtigaM.J., Sanchez-BeatoM., Sanchez-VerdeL., GarciaJ.F., CamachoF.I., FrancoR., PirisM.A.: Analysis of octamer-binding transcription factors Oct2 and Oct1 and their coactivator BOB.1/OBF.1 in lymphomas.Mod Pathol, 15: 211–220, 2002.
7.
CattorettiG., ChangC.C., CechovaK., ZhangJ.D., YeB.H., FaliniB., LouieD.C., OffitK., ChagantiR.S.K., DallafaveraR.: BCL-6 protein is expressed in germinal-center b cells.Blood, 86: 45–53, 1995.
8.
ReeH.J., KadinM.E., KikuchiM., KoY.H., SuzumiyaJ., GoJ.H.: Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: Heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma.Hum Pathol, 30: 403–411, 1999.
9.
CarboneA., GloghiniA., GaidanoG., DallaFaveraR., FaliniB.: BCL-6 protein expression in human peripheral T-cell neoplasms is restricted to CD30(+) anaplastic large-cell lymphomas.Blood, 90: 2445–2450, 1997.
10.
LamantL., De ReyniesA., DuplantierM.M., RickmanD.S., SabourdyF., GiuriatoS., BrugieresL., GaulardP., EspinosE., DelsolG.: Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK(+) subtypes.Blood, 109: 2156–2164, 2007.
11.
HyjekE., ChadburnA., LiuY.F., CesarmanE., KnowlesD.M.: BCL-6 protein is expressed in precursor T-cell lymphoblastic lymphoma and in prenatal and postnatal thymus.Blood, 97: 270–276, 2001.
12.
WascoM.J., FullenD., SuL., MaL.L.: The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders.Hum Pathol, 39: 557–563, 2008.
13.
JacquemierJ., GinestierC., Charafe-JauffretE., BertucciF., BegeT., GeneixJ., BirnbaumD.: Small but high throughput: how “tissue-microarrays” became a favorite tool for pathologists and scientists.Ann Pathol, 23: 623–632, 2003.
14.
MatsuyamaT., GrossmanA., MittruckerH.W., SiderovskiD.P., KieferF., KawakamiT., RichardsonC.D., TaniguchiT., YoshinagaS.K., MakT.W.: Molecular-cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE).Nucleic Acids Res, 23: 2127–2136, 1995.
15.
GrossmanA., MittruckerH.W., NichollJ., SuzukiA., ChungS., AntonioL., SuggsS., SutherlandG.R., SiderovskiD.P., MakT.W.: Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23–p25.Genomics, 37: 229–233, 1996.
16.
MittruckerH.W., MatsuyamaT., GrossmanA., KundigT.M., PotterJ., ShahinianA., WakehamA., PattersonB., OhashiP.S., MakT.W.: Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function.Science, 275: 540–543, 1997.
17.
ChangC.C., McClintockS., ClevelandR.P., TrzpucT., VesoleD.H., LoganB., Kajdacsy-BallaA., PerkinsS.L.: Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma.Am J Surg Pathol, 28: 464–470, 2004.
18.
Dalla-FaveraR., MigliazzaA., ChangC.C., NiuH., PasqualucciL., ButlerM., ShenQ., CattorettiG.: Molecular pathogenesis of B cell malignancy: the role of BCL-6.Curr Topics Microbiol Immunol, 246: 257–263, 1999.
19.
NiuH.F., PietrafesaR., CattorettiG., Dalla-FaveraR.: The Bcl-6 proto-oncogene controls apoptosis in B cells.Blood, 94: 693A, 1999.
20.
KumagaiT., MikiT., KikuchiM., FukudaT., MiyasakaN., KamiyamaR., HirosawaS.: The proto-oncogene Bcl6 inhibits apoptotic cell death in differentiation-induced mouse myogenic cells.Oncogene, 18: 467–475, 1999.
21.
OnizukaT., MoriyamaM., YamochiT., KurodaT., KazamaA., KanazawaN., SatoK., KatoT., OtaH., MoriS.: BCL-6 gene-product, a 92-kD to 98-kD nuclear phosphoprotein, is highly expressed in germinal center b-cells and their neoplastic counterparts.Blood, 86: 28–37, 1995.
22.
FaliniB., BigernaB., PasqualucciL., FizzottiM., MartelliM.F., PileriS., PintoA., CarboneA., VenturiS., PaciniR., CattorettiG., PescarmonaE., LoCocoF., PelicciP.G., AnagnastopoulosI., DallaFaveraR., FlenghiL.: Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease.Blood, 87: 465–471, 1996.
23.
SmockK.J., NelsonM., TrippS.R., SangerW.G., AbromowitchM., CairoM.S., PerkinsS.L.: Characterization of childhood precursor T-lymphoblastic lymphoma by immunophenotyping and fluorescent in situ hybridization: a report from the Children's Oncology Group.Pediatr Blood Cancer, 51: 489–494, 2008.
24.
SteinH., MasonD.Y., GerdesJ., OconnorN., WainscoatJ., PallesenG., GatterK., FaliniB., DelsolG., LemkeH., SchwartingR., LennertK.: The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid-tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.Blood, 66: 848–858, 1985.
