ALDH1, Carbonic Anhydrase 1, and CD2AP: Novel, Diagnostically Useful Immunohistochemical Markers To Identify Erythroid Precursors in Bone Marrow Biopsies.
Marian A Rollins-Raval, Kimberly Fuhrer, Teresa Marafioti, Christine G Roth. University of Pittsburgh Medical Center, PA; University College London, United Kingdom
Background: Characterization of erythroid precursors (EP),especially the most immature subset, in paraffin embedded bone marrow biopsies (BMBX) can be problematic, and lack of identification may preclude establishing the diagnosis of myeloid neoplasms with a prominent immature erythroid component.Flow cytometric studies have reported ALDH1 and carbonic anhydrase 1 (CA1) as useful erythroid markers,however their utility in BMBX is unknown.CD2AP has emerged as a specific marker of plasmacytoid dendritic cells,but has not been comprehensively studied as an erythroid marker.
Design: The immunohistochemical (IHC) expression of ALDH1(clone 44, BD Biosciences),CA1 (clone HRP, Novus Biologicals),& CD2AP (Marafioti Laboratory) was compared with the known erythroid IHC markers glycophorin(clone JC159,Dako) & e-cadherin (clone NCH-38, Dako) in a panel of 55 BMBX:14 cases of reactive erythroid hyperplasia (REH),11 cases of myelodysplasia(MDS),11 cases of acute erythroid leukemia(AEL),15 cases (2 for CD2AP) of non-AEL acute myeloid leukemia (AML),& 4 cases(1 for CD2AP) of negative staging BMBX.Erythroid,myeloid,& megakaryocytic lineages were assessed for reactivity,& positivity within the most morphologically immature erythroid subset was also noted.
Results: EP were identified with all 3 antibodies in all REH,MDS,& negative staging marrows evaluated,& in most cases of AEL(10/11 CD2AP, 11/11 ALDH1 & 11/11 CA1).Although glycophorin positive EP were noted in all cases, the immature EP subset was weak to negative,which was most evident in AEL cases. Immature EP were typically e-cadherin positive,however,2/11 AEL cases were completely negative.ALDH strongly stained the immature EP subset in all cases,with less intense to absent staining in the more morphologically mature forms.CA1 & CD2AP captured the full spectrum of EP, with weaker intensity noted among the immature EP.Weak positivity on a subset of myeloid blasts was seen in 1 case of AML with CA1.Extremely weak staining was noted in a subset of megakaryocytes in 11/39 cases stained with CD2AP, 2/55 cases stained with CA1,& 10/54 cases stained with ALDH1.
Conclusions: CD2AP,CA1,& ALDH1 are novel, diagnostically useful IHC markers for erythroid precursors.ALDH1 is superior to glycophorin and e-cadherin in identifying morphologically immature EP & does not stain myeloid blasts.CA1 and CD2AP stain the full spectrum of EP, with weaker staining of immature EP, although CA1 weak positivity may also rarely be seen in myeloid blasts.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 191, Monday Morning