TTF-1, Napsin A, p63, TRIM29, Desmoglein-3 and CK5: An Evaluation of Sensitivity and Specificity and Correlation of Tumor Grade for Lung Squamous Cell Carcinoma vs. Lung Adenocarcinoma.
David Tacha, Charlie Yu, Thomas Haas. Biocare Medical, LLC, Concord, CA; Mercy Health System, Janesville, WI
Background: The current FDA-approved standard treatment for non-small cell lung cancer is Carboplatin/Taxol/Avastin; however, patients with lung squamous cell carcinoma (SqCC) should not receive Avastin due to a 30% mortality rate by fatal hemoptysis. Antibodies TTF-1 and p63 have been used to differentiate primary lung cancers; however, the need for a more sensitive and specific panel of antibodies to differentiate lung adenocarcinoma (LADC) from lung SqCC is of the utmost importance. In a pilot study, 14 antibodies were evaluated using an IHC method. Based on sensitivity and specificity, a six antibody panel was selected and tested on 132 lung cancer cases. Correlation of this antibody panel with tumor grade was determined.
Design: Formalin-fixed paraffin-embedded TMA tissues for lung cancers were obtained and processed in the usual manner for IHC analysis. The 6 antibody panel was applied to 65 cases of lung SqCC and 67 cases of LADC. Antibodies were optimized with a polymer detection system and visualized with DAB and/or Fast Red.
Results: A six antibody panel was evaluated for sensitivity and specificity (Table 1). Napsin A and TTF-1 provided 91% sensitivity (61/67) and 100% specificity for LADC. The combination of Desmoglein-3, CK5, p63 and TRIM29 provided 93.8% (61/65) sensitivity and 100% specificity for lung SqCC. In all cases, 8.3% (11/132) were unclassified and 7.6% (10/132) were reclassified by the IHC six antibody panel. 5.6% (5/89) of tumors grades 1-2 and 14% (6/43) of grade 3 cases were unclassified by IHC.
|SqCC||4/65 (6%)||0/65 (0%)||61/65 (94%)||61/65 (94%)||54/65 (83%)||55/65 (85%)|
|LADC||51/67 (76%)||60/67 (90%)||11/67 (16%)||8/67 (12%)||0/67 (0%)||0/67 (0%)|