Usefulness of EZH2 and IMP3 in Discriminating High Grade Neuroendocrine Carcinoma from Carcinoids in Small Biopsies and Fine Needle Aspiration Specimens of the Lung
JJ Findeis-Hosey, Q Yang, LA McMahon, BO Spaulding, F Li, H Xu. University of Rochester Medical Center, Rochester, NY; Dako North America, Carpinteria, CA
Background: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 with histone methyltransferase activity. Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) is a 580 amino acid oncofetal RNA-binding protein containing 2 RNA recognition motifs and 4 K homology domains. Our previous studies showed both EZH2 and IMP3 are highly expressed in large and small cell neuroendocrine carcinoma (LCNEC, SCLC) of the lung but not in carcinoids using mainly resected specimens. The aim of this study was to determine if EZH2 and IMP3 are diagnostically useful in their ability to discriminate different neuroendocrine tumors of the lung (NETL) on small biopsies and fine needle aspiration specimens.
Design: Fourteen cases of small biopsies (n=11) and fine needle aspiration specimens (n=3) of NETL, including 5 typical carcinoids (TCs), 1 atypical carcinoid (AC), 2 LCNECs and 5 SCLCs, were immunohistochemically studied using a monoclonal antibody against IMP3 (Dako) and a monoclonal antibody against EZH2 (Leica). The majority of these diagnoses were confirmed on resection. Cytoplasmic staining was considered positive for IMP3 and nuclear staining was considered positive for EZH2. The percentage of positively stained tumor cells was recorded and the staining intensity was graded as weak, moderate, or strong. A p value of <0.05, as determined by two-tailed Fisher exact test, was considered statistically significant.
Results: Immunohistochemical studies showed strong and diffuse EZH2 and IMP3 staining in all 2 LCNECs and 5 SCLCs. Among them, 4 cases had severe crush artifact. Conversely, there was no EZH2 staining in all 5 TCs and the 1 AC. There was weak IMP3 staining in 30% of tumor cells in 1 (20%) of 5 TCs. There was no IMP3 staining in the 1 AC case. EZH2 and IMP3 expression was significantly higher (p<0.01) in high grade neuroendocrine carcinoma than carcinoids (100%, n=7 and 100%, n=7 versus 0%, n=6 and 17%, n=6, respectively).
Conclusions: Our study demonstrates the usefulness of immunohistochemical detection of EZH2 and IMP3 in aiding in the discrimination of high grade neuroendocrine carcinoma from carcinoids in small biopsies and fine needle aspirations specimens of the lung which may have limited diagnostic material present or which may have a severe crush artifact.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 239, Wednesday Morning