IMP-3 and Ki-67 Expression in Neuroendocrine Tumors of the Lung.
Larry Zhao, Armando Fraire, Philip Cagle, Timothy Allen, Kenneth Rock, Dina Kandil. University of Massachusetts Medical School, Worcester; The Methodist Hospital, Houston, TX; University of Texas, Tyler
Background: Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) plays a key role in multiple cancers. Ki-67 is a nuclear protein involved in cell proliferation. IMP3 has been shown to have higher expression in high grade tumors and to be a poor prognostic marker for some others. Ki-67 has been reported as a helpful biomarker in differentiating carcinoid tumors from small cell carcinomas (SCC) of the lung. In this study, we explore for the first time the usefulness of IMP-3 in discriminating pulmonary carcinoid tumors from SCC. To our knowledge, this is the first study to evaluate the expression of both IMP3 and Ki-67 in pulmonary neuroendocrine tumors.
Design: Sixty-seven tissue micro-array cases were retrieved from the surgical pathology files of a large academic institution. These included 40 cases of carcinoid tumors (39 typical and 1 atypical) and 27 SCC. All cases were stained with antibodies against IMP3 and Ki-67 proteins, and evaluated independently by 2 observers. IMP3 expression was divided into 2 categories: negative (absent or weak cytoplasmic staining) and positive (moderate or strong cytoplasmic staining with membranous accentuation). Ki-67 expression was scored as negative or low (0-20% positivity) or high (> 20 %).
Results: IMP-3 was expressed in 60% (16/27) of SCC cases. KI-67 expression was high in 48% (13/27) of SCC cases. Combined, IMP-3 and KI67 were expressed in 30% (8/27) of SCC cases. In carcinoid tumors, IMP-3 was expressed in only 5% (2/39) cases, while Ki-67 expression was expressed in 2.5% (1/39) cases. The atypical carcinoid case was positive for both IMP-3 and ki-67. None of the typical carcinoid cases showed positivity for both markers.
Conclusions: In this study, IMP-3 is shown to have higher sensitivity than KI-67 in SCC (60 vs. 48%) and slightly lower specificity (95 vs. 97.5%). However, the combined sensitivity of both markers in SCC was 30%. Our data suggest that IMP-3 is preferentially expressed in SCC than in typical carcinoids. Our findings further suggest that neuroendocrine tumors with equivocal features of SCC but expressing both IMP3 and Ki-67 can be safely classified as SCC.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 251, Wednesday Morning