Evaluation of Intercellular Adhesion Molecule 1 (ICAM-1), a CD15-Associated Glycoprotein for the Diagnostic Workup of Classical Hodgkin Lymphoma
Noah A Brown, Dafydd Thomas, Farah Keyoumarsi, Kojo SJ Elenitoba-Johnson, Megan S Lim. University of Michigan, Ann Arbor, MI
Background: Classical Hodgkin lymphoma (CHL) is one of the most prevalent lymphomas in Western countries. CD15 is the most specific marker for this type of lymphoma and immunohistochemical staining for CD15 is routinely employed for clinical diagnosis. However, the expression of CD15 is variable and the sensitivity ranges from 60% to 76%. Recently, our glycoproteomic profiling identified intercellular adhesion molecule 1 (ICAM-1), one of three carrier proteins of the CD15 epitope in CHL cell lines. ICAM-1 and its ligand LFA-1 play a role in the complex interactions between Hodgkin-Reed Sternberg (HRS) cells and the inflammatory milieu. In this study, we sought to evaluate the immunohistochemical expression of ICAM-1 in CHL and non-Hodgkin lymphomas considered in the differential diagnosis.
Design: Immunohistochemical analysis using a monoclonal antibody for ICAM-1 was performed on tissue microarrays containing 203 cases of CHL, 41 cases of anaplastic large cell lymphoma (ALCL), 125 cases of diffuse large B cell lymphoma, 12 cases of primary mediastinal large B cell lymphoma (PMBL) and 24 cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). CHL arrays were also stained with a CD15 monoclonal antibody. Arrays were scored based on the percentage and strength of immunoreactive neoplastic cells. Positive cases were those with ≥ 50% neoplastic cells showing staining at least as strong as background histiocytes.
Results: ICAM-1 is expressed in 91.1% of CHL (185/203) compared to 53.7% of ALCL (p<0.0001), 17.6% of DLBCL (p<0.0001), 33.3% of PMBL (p<0.0001) and 50% of NLPHL (p<0.0001). The specificity in this cohort is 70.3%. The sensitivity of CD15 in the same cohort is 62.1%, significantly lower than that of ICAM-1 (p<0.001). Of the CHL cases which were negative for ICAM-1, only one was positive for CD15.
Conclusions: ICAM-1, a glycoprotein associated with CD15, is expressed in a majority of cases of CHL and in higher frequency than CD15. This protein is also expressed in a proportion of non-Hodgkin lymphomas particularly anaplastic large cell lymphoma. While the expression of ICAM-1 is observed more frequently in CHL, the addition of the CD15 sugar moiety appears more specific to CHL. Additional work is required to determine the diagnostic utility of ICAM-1 in conjunction with known markers as well as to investigate the expression of other CD15 carrier proteins.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 204, Monday Morning