Different expression of EZH2, BMI1 and Ki67 in low and high grade neuroendocrine tumors of the lung

Article type: Research Article

Authors: Bondgaard, Anna-Louise Reinert Ørsum^{a; b; *} | Poulsen, Thomas Tuxen^a | Poulsen, Hans Skovgaard^a | Skov, Birgit Guldhammer^b

Affiliations: [a] Department of Radiation Biology, Finsen Center, Copenhagen University Hospital, Copenhagen, Denmark | [b] Department of Pathology, Copenhagen University Hospital/Team Bispebjerg, Copenhagen, Denmark

Correspondence: [*] Corresponding author: Anna-Louise Reinert Ørsum Bondgaard, Copenhagen University Hospital/team Bispebjerg, Department of Pathology, Section 19, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark. Tel.: +45 26 82 26 19; E-mail: [email protected].

Abstract: Background:Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated their expression in 96 NELT and correlated it to clinical features including survival. Materials and methods:Paraffin embedded material from 50 typical carcinoids (TC), 13 atypical carcinoids (AC), 23 large cell neuroendocrine carcinomas (LCNEC) and 10 small cell lung carcinomas (SCLC) was evaluated by immunohistochemisty. Results:Significantly higher expression of EZH2 was found in high grade NELT (LCNEC + SCLC) versus low grade NELT (TC + AC) (p < 0.0001). High expression of BMI1 was observed in low grade NELT (TC + AC) in contrast to the expression in high grade NELT (LCNEC+SCLC) (p=0.004). In multivariate models, diagnosis was the strongest predictor of survival. Conclusion:The immunohistochemical expression of EZH2 and BMI1 are significantly different in low versus high grade NELT. This difference might be related to NELT tumorigenesis. These markers have no independent prognostic impact in NELT. Whether EZH2 could become target in new treatments strategies against NELT remains to be elucidated.

Keywords: Neuroendocrine tumors of the lung, small-cell lung cancer, carcinoids, large cell neuroendocrine carcinoma, EZH2, BMI1, Ki67

DOI: 10.3233/CBM-2012-0269

Journal: Cancer Biomarkers, vol. 11, no. 2-3, pp. 123-128, 2012