ERBB2 Overexpression Correlates with Non-Germinal Center Subtype of Diffuse Large B-Cell Lymphoma
Olga V Danilova, Alexey V Danilov, Prabhjot Kaur. Dartmouth-Hitchcock Medical Center, Lebanon, NH; Geisel School of Medicine at Dartmouth, Hanover, NH; Norris Cotton Cancer Center, Lebanon, NH
Background: Diffuse large B-Cell lymphoma (DLBCL) is the most common high-grade lymphoma in the western world. The pathogenesis of this disease remains elusive with 30-50% of the patients succumbing to the disease within 5 years of diagnosis, suggesting the need for reliable prognostic factors and novel therapeutic approaches. ERBB2 /HER2 is the member of epidermal growth factor family of transmembrane receptors. Aberrant ERBB2 expression or function has been shown in breast, gastric, ovarian, and other type of cancers. ERBB2 overexpression is associated with poor prognosis in breast malignancies. Anti-ERBB2 monoclonal antibodies are now widely used in treatment of ERBB2-positive breast carcinoma. There is paucity of reports on the prognostic value of ERBB2 in lymphoma. In this study we analyzed the protein expression of ERBB2 and established its correlations with survival and known prognostic factors in DLBCL.
Design: A tissue microarray, containing 79 cases of DLBCL, diagnosed between 1999 and 2008, were analyzed by immunohistochemistry for ERBB2 (Biogenex, clone EP1045Y 1:30 dilution). The intensity of membranous and cytoplasmic staining was subjectively graded as negative, weak or strong. The distribution of staining of the tumor cells was graded as <30% and >30%. ERBB2 overexpression was defined as strong staining of >30% of lymphoma cells. The results of staining were correlated with overall survival, IPI score, and DLBCL subtype (germinal center [GC] vs non-germinal center [Non-GC]). The DLBCL was subtyped by immunostaining with CD10, MUM1 and Bcl6 according to WHO 2008 criteria. Chi-square test was used to analyze the results.
Results: The patient population included 39 women and 40 men with median age 59.5 ± 19.3 yrs. Out of 79 patients, 30 died of disease, and 49 remained in complete remission after a median follow-up of 4.7 years (1.5-14.0 years). ERBB2 was expressed in 75/79 cases. ERBB2 expression did not correlate with survival or IPI. However, 51% non-GC (22/43) and 25% of GC (9/36) showed diffuse strong expression of ERBB2 (Chi2=5.626, p=0.017).
Conclusions: Expression of ERBB2 emphasizes the role of EGFR pathways in the pathogenesis of DLBCL. Its relative overexpression in Non-GC subgroup may contribute to the more aggressive course typically seen in this group of patients. This finding has possible therapeutic implications and requires validation in larger studies.
Monday, March 4, 2013 1:00 PM
Poster Session II # 196, Monday Afternoon