PLZF Immunstaining Inversely Correlates with Aggressiveness in Pulmonary Neuroendocrine Tumors
Jaclyn F Hechtman, Yayoi Kinoshita, Mary B Beasley, David E Burstein. Mount Sinai School of Medicine, New York, NY
Background: Pulmonary neuroendocrine tumors (PNT) include the low grade typical carcinoid (TC) the intermediate grade atypical carcinoid (AC), and the two high grade tumors, large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). While these tumors exhibit differing biologic behavior, they may be problematic to separate on small biopsy or cytology specimens. We surveyed a spectrum of PNTs for immunohistochemical detection of PLZF (Promyelocytic leukemia zinc finger), a transcriptional repressor with tumor suppressor-like activity. PLZF has been most extensively studied in leukemia; very few studies in solid tumors have been performed.
Design: Immunohistochemical staining for monoclonal anti-PLZF (D-9, 1:1000, Santa Cruz Biotechnology, Santa Cruz, CA) was performed on a total of 60 representative blocks from archival cases of carcinoid tumorlets (n=13); TC (n=18); AC (n=7); SCLC (n=18), LCNEC (n=4). Immunohistochemical staining intensity (0 to 3+), intracellular localization, and percent of immunoreactive tumor cells were recorded.
Results: Normal Type 1 alveolar epithelial cells displayed nuclear staining, serving as an internal positive control. All 13 tumorlets had nuclear immunoreactivity with 2-3+ intensity and staining in 95% to 100% of cells; 8 also displayed cytoplasmic immunoreactivity (1+ intensity; 95 to 100% of cells). Of the 18 TC, 17 had nuclear immunoreactivity with 2-3+ intensity staining of 10-100% of tumor cells (average = 70%). 16 also had cytoplasmic immunoreactivity, 1-2+ in intensity, involving 10-100% of cells (average=63%). Of 7 AC, 5 had nuclear immunoreactivity, intensity 2-3+, involving 20-80% of cells, (average=35%). 6 of these had cytoplasmic immunoreactivity with 1-2+ intensity, involving 30% to 100% of cells (average= 55%). All cases of SCLC and LCNEC were completely unreactive.
Conclusions: The percent of nuclear expression of PLZF in PNTs has an inverse correlation with grade. No staining was observed in either LCNEC or SCLC, suggesting that dysregulation of this transcriptional repressor may play a role in the aggressive behavior of the high grade PNTs. Further, the differential expression of PLZF appears to have utility in classification of PNTs. In particular, positive PLZF staining appears to exclude a diagnosis of SCLC or LCNEC.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 294, Tuesday Afternoon