Napsin A Expression in Human Tumors and Normal Tissues.

Sören Weidemann,Ria Uhlig,Hendrina Contreras,Christoph Fraune,Katharina Möller,Patrick Lebok,Till Krech,Franziska Büscheck,Martina Kluth,Waldemar Wilczak,David Dum,Michael Rink,Christian Bernreuther,Ronald Simon,Andrea Hinsch,Anne Menz,Rainer Krech,Guido Sauter,Andreas M Luebke,Doris Höflmayer,Stefan Steurer,Jan Lukas Böhle,Andreas Marx,Sarah Minner,Eike Burandt,Till S Clauditz ,Claudia Hube‐Magg

doi:10.3389/pore.2021.613099

Abstract

Background: Novel aspartic proteinase of the pepsin family A (Napsin A, TAO1/TAO2) is a functional aspartic proteinase which is involved in the maturation of prosurfactant protein B in type II pneumocytes and the lysosomal protein catabolism in renal cells. Napsin A is highly expressed in adenocarcinomas of the lung and is thus commonly used to affirm this diagnosis. However, studies have shown that other tumors can also express Napsin A. Methods: To comprehensively determine Napsin A expression in normal and tumor tissue, 11,957 samples from 115 different tumor types and subtypes as well as 500 samples of 76 different normal tissue types were evaluable by immunohistochemistry on tissue microarrays. Results: Napsin A expression was present in 16 different tumor types. Adenocarcinoma of the lung (85.6%), clear cell adenocarcinoma of the ovary (71.7%), clear cell adenocarcinoma of the endometrium (42.8%), papillary renal cell carcinoma (40.2%), clear cell (tubulo) papillary renal cell carcinoma (16.7%), endometrial serous carcinoma (9.3%), papillary thyroid carcinoma (9.3%) and clear cell renal cell carcinoma (8.2%) were among the tumors with the highest prevalence of Napsin A positivity. In papillary and clear cell renal cell carcinoma, reduced Napsin A expression was linked to adverse clinic-pathological features (p ≤ 0.03). Conclusion: This methodical approach enabled us to identify a ranking order of tumors according to their relative prevalence of Napsin A expression. The data also show that loss of Napsin A is linked to tumor dedifferentiation in renal cell carcinomas.

Highlights

Novel aspartic proteinase of the pepsin family A (Napsin A, TAO1/ TAO2) belongs to the peptidase A1 family, such as Cathepsin E, renin, and pepsin and is encoded by the NAPSA gene located at chromosome 19q13.3 [1,2,3]
A total of 11,957 (81.4%) of 14,692 tumor samples and 500 (82.2%) of 608 normal samples were interpretable for Napsin A immunostaining in our tissue microarray (TMA) analysis
A moderate to strong (2+/3+) cytoplasmic Napsin A staining was found in pneumocytes and alveolar macrophages of the lung (Figure 1A), and the renal medulla and cortex of the kidney (Figure 1B)

Summary

Introduction

Novel aspartic proteinase of the pepsin family A (Napsin A, TAO1/ TAO2) belongs to the peptidase A1 family, such as Cathepsin E, renin, and pepsin and is encoded by the NAPSA gene located at chromosome 19q13.3 [1,2,3]. Napsin A is mainly expressed in the cytoplasm of type II pneumocytes, intra-alveolar macrophages, proximal and convoluted renal tubules, and pancreatic acini and ducts [4, 5] as well as adenocarcinomas of the lung, papillary renal cell carcinomas, and ovarian clear cell carcinomas [1, 6, 7]. Napsin A is involved in the maturation of prosurfactant protein B in type II pneumocytes [8], potentially in phagocytosis by macrophages [3] and the lysosomal protein catabolism in renal cells [9]. Novel aspartic proteinase of the pepsin family A (Napsin A, TAO1/TAO2) is a functional aspartic proteinase which is involved in the maturation of prosurfactant protein B in type II pneumocytes and the lysosomal protein catabolism in renal cells. Studies have shown that other tumors can express Napsin A

Methods

Results

Conclusion