Evaluation of Napsin A, Cytokeratin 5/6, p63, and Thyroid Transcription Factor 1 in Adenocarcinoma Versus Squamous Cell Carcinoma of the Lung

Abstract

N Context.-The distinction of lung adenocarcinoma from other types of primary lung malignancies is important clinically. Accurate morphologic classification is often hindered because 70% of lung cancers are diagnosed on limited fine-needle aspiration or transbronchial biopsy specimens. Although thyroid transcription factor 1 (TTF-1) has historically been the most specific marker for lung adenocarcinoma, a relatively new marker, napsin A, has recently been shown to be more sensitive and specific than TTF-1.Objective.-To find the most cost-effective panel to reliably distinguish lung adenocarcinoma from squamous cell carcinoma.Design.-A total of 291 lung cancers were evaluated morphologically (197 adenocarcinomas [75%]; 66 squamous cell carcinomas [25%]; 28 cases could not be classified into either and were dropped). Immunohistochemistry for napsin A, Cytokeratin 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.Results.-Napsin A had 83% sensitivity and 98% specificity and TTF-1 had 60% sensitivity and 98% specificity for adenocarcinoma. Cytokeratin 5/6 had 53% sensitivity and 96% specificity and p63 had 95% sensitivity and 86% specificity for squamous cell carcinoma. A panel of napsin A and p63 has a specificity of 94% and a sensitivity of 96% for distinguishing adenocarcinoma from squamous cell carcinoma.Conclusions.-The source of the antibody is important in avoiding false-negative results. The most cost-effective tissue-preserving panel for small biopsy specimens in the differential diagnosis of lung adenocarcinoma versus squamous cell carcinoma is a combination of p63 and napsin A.

Napsin A is a specific marker for ovarian clear cell adenocarcinoma

“…Thus, we consider napsin A to be another suitable marker to specifically distinguish clear cell adenocarcinoma from other ovarian tumors with a relatively high sensitivity. Furthermore, because napsin A is an established marker for lung adenocarcinomas, [7][8][9][10][11][12][13] we assume that napsin A immunostaining will be easily applied to routine surgical pathology specimens in laboratories. In this study, we determined the criteria for positive napsin A immunostaining as 410% tumor area for differential diagnosis between histological subtypes of ovarian adenocarcinomas, and given that focal positivity is observed in those other than clear cell adenocarcinoma, careful interpretation is required when applying this method on small biopsy specimen.…”

“…[1][2][3][4] Napsin A has a role in processing pulmonary surfactant B protein produced by alveolar type II pneumocytes; 5,6 thus, it has been reported to be a good diagnostic marker for the confirmation of primary lung adenocarcinoma together with thyroid transcription factor 1 (TTF-1). [7][8][9][10][11][12][13] Expression of napsin A is also observed in the fetal kidney 14 and proximal tubules of the adult kidney, where it is most likely involved in protein catabolism. 15 In neoplasms other than lung cancer, napsin A expression is most frequently observed in papillary renal carcinoma (79%), followed by other subtypes of renal cell carcinoma and thyroid carcinoma.…”

Immunostaining for thyroid transcription factor 1, Napsin A, p40, and cytokeratin 5 aids in differential diagnosis of non-small cell lung carcinoma

“…The value of TTF-1 as a distinct marker of adenocarcinomas, using immunocytochemistry, has been demonstrated in a number of reports (10,14). In the present study, the expression of p40 and TTF-1 was investigated in conjunction with the expression of CAM5.2, napsin A, CK5/6 and CK5, a combination that has been shown to exhibit effective diagnostic properties (3,10). As the results based on conventional tests of sensitivity and specificity were considered to be ineffective in determining a differential diagnosis, a new method of scoring using objective values was evaluated.…”

“…Additionally, in lung cancer, an objective method is required for drug selection (2). Therefore, it is hypothesized that the use of immunostaining for differentiation is essential when tumor samples are limited (3). In the present study, immunostaining of cytological specimens was evaluated for its ability to clearly Immunostaining for thyroid transcription factor 1, Napsin A, p40, and cytokeratin 5 aids in differential diagnosis of non-small cell lung carcinoma distinguish squamous cell carcinoma from adenocarcinoma.…”

Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

“…19,33,34 For limited biopsy samples, we recommend an initial IHC panel of TTF-1 and p40. If needed, additional squamous markers (p63 and CK5/6) or glandular markers (napsin A and CK7) may be added.…”