Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma

Abstract

Napsin A is an aspartic proteinase expressed in lung and kidney. We have reported that napsin A is expressed in type II pneumocytes and in adenocarcinomas of the lung. The expression of napsin was examined in 118 lung tissues including 16 metastases by in situ hybridisation. Napsin was expressed in the tumour cell compartment in 33 of 39 adenocarcinomas (84.6%), in two of 11 large cell carcinomas and in one lung metastasis of a renal cell carcinoma. Expression of napsin was found to be associated with a high degree of differentiation in adenocarcinoma. Immunohistochemistry was performed for three proteins currently used as markers for lung adenocarcinoma : surfactant protein-A, surfactant protein-B and thyroid transcription factor-1. Thyroid transcription factor-1 showed the same sensitivity (84.6%) as napsin for adenocarcinoma, whereas surfactant protein-A and surfactant protein-B showed lower sensitivities. Among these markers, napsin showed the highest specificity (94.3%) for adenocarcinoma in nonsmall cell lung carcinoma. We conclude that napsin is a promising marker for the diagnosis of primary lung adenocarcinoma. Lung cancer is the leading cause of cancer mortality in the world and one of the top incidence of cancers in Europe and the US (Black et al, 1997;Wingo et al, 1999). Lung cancer has a poor prognosis and even for patients with operable disease, the 5-year survival rate is 14% in the US (Landis et al, 1998). Nonsmall cell lung cancer (NSCLC), essentially consisting of adenocarcinoma, squamous cell carcinoma (epidermoid carcinoma) and large cell carcinoma, accounts for approximately 80% of all lung cancers (Travis et al, 1995). The incidence of pulmonary adenocarcinoma has been increasing and adenocarcinoma is now the most common histologic subtype in the US (Charloux et al, 1997;Landis et al, 1998).The lung is also a common site for metastases from tumours growing at other sites. From a clinical point of view, it is important to distinguish between primary lung adenocarcinoma and metastatic adenocarcinoma in the lung since treatment protocols differ depending on the origin. Primary lung adenocarcinoma develops from type II pneumocytes and from bronchiolar nonciliated secretory cells (Clara cells). Surfactant apoproteins, including surfactant protein-A (Sp-A) and surfactant protein-B (Sp-B) are used as markers for lung adenocarcinoma and thyroid transcription factor-1 (TTF-1) is used as a marker for lung adenocarcinoma, large cell carcinoma, small cell carcinoma and thyroid carcinoma (Kaufmann and Dietel, 2000b).Recently, a new aspartic proteinase, napsin A, was cloned and shown to be expressed in lung and kidney (Tatnell et al, 1998). Our group and another group have shown that napsin A is identical to the protein spots TAO1/TAO2 detected by two-dimensional gel electrophoresis of lung adenocarcinoma, and that napsin A is expressed in type II pneumocytes and lung adenocarcinomas (Chuman et al, 1999;Hirano et al, 2000). However, the detailed expression patterns of napsin A in association with other m...

Selective Immunohistochemical Markers to Distinguish Between Metastatic High-Grade Urothelial Carcinoma and Primary Poorly Differentiated Invasive Squamous Cell Carcinoma of the Lung

“…7,[17][18][19][20] Neither antibodies against napsin A nor antibodies against surfactant protein A were found to be helpful for distinguishing these 2 tumor types, as both failed to show significant expression of either protein. Expression levels of napsin A and surfactant protein A detected in the primary pulmonary SCC cases from the present study are in agreement with results published by Ueno et al 21 While the immunohistochemical data from the series of paired tumors could not definitively identify the presence of synchronous primary urothelial and primary pulmo- nary lesions among the 30-patient cohort, two of the lung lesions from the paired case series displayed an immunophenotype more similar to that of the typical primary pulmonary squamous cell carcinoma than the typical primary invasive bladder urothelial carcinoma in our series (case 8 and case 23; Table 4). Involvement by metastatic urothelial carcinoma was used as a descriptor in 77% of the pulmonary lesions, based upon the histomorphologic and clinical features present at the time of diagnosis of the lung tumor.…”

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.…”

Value of napsin A and thyroid transcription factor-1 in the identification of primary lung adenocarcinoma

“…The stained slides were observed microscopically by two experienced pathologists. results were scored in accordance with the criteria of Ueno et al (6) and expressed on a plus-minus scale based on the proportion of tumor cells stained: -, 0-10%; ++, 10-50% and +++, 50-100%.…”

“…In normal lung it has been found to be present in type Ⅱ pneumocytes and to be involved in the maturation of the biologically active surfactant protein B (SP-B) (5). Studies have shown its expression in primary lung adenocarcinoma; thus, napsin A can be used in defining primary adenocarcinoma of the lung (6,7). Nevertheless, compared with other markers, there has been limited research involving napsin A.…”