Abstract
Background and Aims: Distinguishing low/intermediate grade neuroendocrine carcinoma (carcinoid and atypical carcinoid) from a high grade neuroendocrine carcinoma [small cell carcinoma and large cell neuroendocrine carcinoma (LCNEC)] of the lung can be difficult, especially in small biopsy specimens. Patients diagnosed with a low/intermediate grade carcinoma would be treated surgically white patients diagnosed with small cell carcinoma with chemotherapy. Biomarkers may increase the diagnostic accuracy.
Methods: We studied 42 consecutive cases of neuroendocrine tumors of the lung (20 small cell carcinomas, 7 large cell neuroendocrine carcinomas, 12 carcinoids and 3 atypical carcinoids) with the objective of comparing the expression of the panel of biomarkers (CD117, KOC, Ki-67, pVHL and p16) between the low and high grade neuroendocrine tumors of the lung. Tissue microarrays were constructed and expression of each biomarker was evaluated using immunohistochemistry. Staining was standardized and scored as “0” = Negative, “1+” = Focal, “2+” = 30–49% cells staining and “3+” = 50–100% cells staining positively. For the purpose of the present study, a specimen scored as “0” or “1+” was classified as negative, while a specimen scored as “2+” or “3+” was considered positive. In estimating the likelihood of expression of the biomarkers, specimens were categorized into low grade and high grade. Two-sided non-parametric statistical analyses were performed using the SAS v. 9.3 (SAS Institute, Cary, NC).
Results: Expression of KOC, p16, pVHL and Ki67 was significantly different between low and high grade tumor categories. No significant difference was observed for CD117. 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% 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 less in high grade tumors (OR=0.31 95% CI 0.12–0.84, p=.022). We detected a statistically significant probability of joint overexpression of three of the biomarkers [p16 and KOC and Ki_67] in small cell carcinoma relative to atypical carcinoids (OR=2.53. 95% CI 1.24–5.17, p=.011).
Conclusions: Findings from this pilot project suggest that Ki-67, KOC and p16 are an effective antibody panel in differentiating high grade neuroendocrine carcinoma from low/intermediate grade neuroendocrine carcinoma.
- Received May 27, 2010.
- Accepted May 27, 2010.
