Evaluation of Napsin A, CK 5/6, p63, and TTF-1 in Adenocarcinoma (ACA) vs. Squamous Cell Carcinoma (SCC) of the Lung.
Kenneth Whithaus, Junya Fukuoka, Jaishree S Jagirdar. University of Texas Helth Science Center at San Antonio; University of Toyama, Japan
Background: The distinction of lung ACA from other types of primary lung malignancies is clinically important because recent advances in treatment of lung cancer suggest that lung ACA in non smokers has a high response rate to Epidermal Growth Factor Receptors-Tyrosine Kinase inhibitors. In Addition certain antiangiogenic agents are contraindicated in SCC due to risk of bleeding. Studies have evaluated different panels of immunohistochemical markers in the distinction of ACA from SCC of the lung, with varying specificity and sensitivity. Accurate morphologic classification is further hindered because 70% of lung cancers are diagnosed on limited FNA or transbronchial biopsy specimens. Panels have included combinations of immunohistochemcal markers, TTF-1/ CEA for ACA, CK5/6, p63/ Desmoglein 3 for SCC. While TTF-1 has historically been the most specific marker for lung ACA, a relatively new marker, Napsin A (a functional aspartic proteinase involved in the maturation of pro-surfactant protein-B in type II pneumocytes), has recently been shown to be more sensitive and specific than TTF-1. A commercially available costly panel of 5 antibodies has been used in this endeavor. We wish to find the most cost effective and tissue preserving panel in reliably distinguishing lung ACA from SCC.
Design: A Total of 291 lung cancers were evaluated morphologically (ACA=197; SCC=66; 28 large cell carcinomas). Immunohistocmemistry for Napsin A, CK 5/6, p63, and TTF-1 was performed on a formalin fixed tissue microarray obtained from Toyama, Japan. Cases were scored as positive or negative against a negative control. Immunohistochemistry was performed at UTHSCSA IHC Laboratory. Antibodies used included Napsin A (Cell Marque, Prediluted), Cytokeratin 5/6 (Cell Marque, Prediluted), p63 (Biocare Medical, Prediluted), TTF-1 (Dako 1:80). All slides were treated for 30 minutes at 100 degrees and then allowed to cool down for 20 minutes using the Revel antigen retrieval solution (Biocare Medical). The slides were incubated in primary antibody for 1 hour followed by detection with Biocare Medicals Mach 2 universal polymer-HRP for 30 minutes and developed with DAB.
|MARKER||ACA (SEN.)||ACA (SPEC.)||SCC (SEN)||SCC (SPEC.)||LCC|