Abstract 829: A panel of three biomarkers for differentiating high from low grade neuroendocrine tumors of the lung: Findings from a Pilot Project

Abstract

Abstract Background: Distinguishing low/intermediate grade (carcinoid & atypical carcinoid) from high grade neuroendocrine carcinoma [small cell carcinoma & large cell neuroendocrine carcinoma (LCNEC)] of the lung can be difficult, especially in small biopsy specimens. This distinction is important for appropriate planning of a patient's course of treatment. Expression of biomarkers can be used to improve the precision of a differential diagnosis. We evaluated the expression of a panel of 5 biomarkers: CD117, a cytokine receptor, and KOC, a member of the insulin-like growth factor messenger RNA-binding protein family; Ki-67, a proliferation marker; the von Hippel-Lindau gene product (pVHL) and p16, 2 tumor suppresser markers. This panel was chosen because of their biological functions and their differential expression in low/intermediate vs. high grade cacinomas. Method: We studied 42 consecutive cases of carcinoma of the lung (20 small cell carcinomas, 7 large cell neuroendocrine carcinomas, 12 carcinoids and 3 atypical carcinoids). Tissue microarrays were constructed and biomarkers’ expressions were evaluated immunohistochemically. Staining was standardized and scored as “0+” = Negative, “1+” = Focal, “2+” = 30-49% cells staining and “3+” = 50-100% cells staining positively. A specimen scored as “0” / “1+” was classified as negative, while a specimen scored as “2+” / “3+” was considered positive. The likelihood of expression of the panel by histopathologic diagnosis was estimated using two-sided non-parametric statistical techniques. Results: Statistically significant differential expression for KOC, p16, pVHL and Ki-67 between low and high grade tumors was seen, but no significant difference for CD117 was detected. High grade tumors showed greater expression of Ki-67 (OR=13.85, 95% CI 3.34-57.47, p=0.0003), p16 (OR=3.52, 95% CI 1.75-7.11, p=0.0004) and KOC (OR=4.24, 95% CI 1.88-9.56, p=0.0005); while, pVHL expression was lower in high relative to low/intermediate grade tumors (OR=0.31, 95% CI 0.12-0.84, p=.022). We detected a statistically significant probability of the joint over-expression of 3 of the 5 biomarkers [p16 and KOC and Ki-67] in LCNEC relative to atypical carcinoids (OR=2.53, 95% CI 1.24-5.17, p=.011). Conclusion: Findings suggest that Ki-67, KOC and p16 is an effective antibody panel in differentiating high from low/intermediate grade neuroendocrine carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 829.