Abstract
10579 Background: CUP involves extensive use of immunohistochemical (IHC) stains because no individual marker is highly both site specific or sensitive. IHC algorithms lack standardization and may even eliminate actual primary sites. Extensive validation studies with gene expression profiling (GEP) has shown it be a new diagnostic technique that further contributes tumor site location in CUP. Thyroid transcription factor-1 (TTF-1) IHC stain is commonly used to identify the pulmonary origin of CUP (particularly adenocarcinoma) and is often used to exclude lung primary in CUP patients. This study evaluates the utility of TTF-1 staining in lung primaries (specifically non-small cell lung carcinoma - NSCLC) of CUP to GEP testing. Methods: This retrospective study contains data obtained from a registry of physicians who received the GEP-based Tissue of Origin (TOO) test (Pathwork Diagnostic, Sunnyvale, CA) between 07/2009 and 12/2009 on CUP cases. Sixty-six physicians contributed 111 TOO test cases. Only cases that had TTF-1 done were included for analysis and these were compared to TOO NSCLC results. Results: Out of 111 cases, there were 73 analyzable TTF-1 results with 12 cases of NSCLC and 61 cases of non-NSCLC by TOO (see TABLE). Assuming that the results of TOO testing accurately indicated the true primary site, the sensitivity and specificity of TTF-1 was 50% and 90%, respectively. The false negative rate was 50%, indicating that half of the identified NSCLC cases in this series had negative TTF-1. On the other hand, 10% of the 61 cases with primaries other than NSCLC (none of whom had thyroid cancer), had positive TTF-1. The “false positive” TTF-1 cases comprised 4 ovarian, 1 breast and 1 colorectal as the site of origin. Conclusions: TTF-1 has limited utility in identifying NSCLC in the setting of CUP. Half of NSCLCs identified by TOO testing had negative TTF-1, and 10% of non-lung primaries were TTF-1 positive. Negative TTF-1 should not be used to exclude NSCLC in the workup of CUP. [Table: see text]
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