For metastatic carcinomas of thyroid and lung origin, napsin A was detected in 39.0% of thyroid carcinomas in contrast to 88.0% in cases of lung adenocarcinomas.
Using this method we demonstrate that lung napsin A in many mammals is a heterogeneous enzyme with a characteristic ladder-like appearance in SDS-PAGE that might be caused by proteolytically processed N- and/or C-termini, in contrast to the more homogeneous form found in kidneys and primary lung adenocarcinoma.
Primary lung adenocarcinomas expressed TTF-1 in 90% and napsin A in 84% of the cases, whereas 10% were positive for p63, 7% for CDX2, 2% for CK20, and 2% for GATA3.
In multivariate analysis, the best markers, enabling the distinction between SOX10-negative TNBC and TTF1 and Napsin A-negative LA were GATA3 (odds ratio=33.5; 95% confidence interval, 7.3-153.5; P<0.0001) and GCDFP15 (odds ratio=31.7; 95% confidence interval, 6.9-145.6; P<0.0001).
The sensitivity, specificity and accuracy of negative MUC21 expression for differentiating epithelioid mesothelioma from lung adenocarcinoma were 97%, 96%, and 96%, respectively; these are similar to those of carcinoembryonic antigen and claudin-4, and better than those of thyroid transcription factor-1, napsin-A, and mucin 4.
TTF-1 and napsin A for lung adenocarcinoma, p40 for squamous lung cancer, GATA3 and mammaglobin for breast cancer, or synaptophysin and chromogranin A for neuroendocrine tumors).
TTF-1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung.
To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma.
In summary, KRAS G12C mutations, TTF-1, and napsin A were associated with primary lung adenocarcinoma, whereas KRAS G12R mutations, CK20, and CDX2 favored pancreatic adenocarcinoma.
However, Napsin-A immunoreactivity has the potential to misguide a pathologist to conclude a metastasis from renal, thyroid, or endometrial carcinoma as a primary lung adenocarcinoma.
In this context, we confirmed the expression of napsin A in primary lung adenocarcinoma using reverse-transcription polymerare chain reaction (RT-PCR) and showed that the TA02 mAbs reacted with glutathione-S-transferase (GST)-napsin A fusion protein.