Pulmonary large cell neuroendocrine carcinoma (LCNEC) is usually a highly aggressive
May 11, 2019
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is usually a highly aggressive malignancy, which was recently found to comprise three major genomic subsets: small cell carcinoma-like, non-small cell carcinoma (predominantly adenocarcinoma)-like and carcinoid-like. an expression profiling study.7 In both studies, it was noted that some adeno-like tumors exhibited expression of a relatively recent pulmonary exocrine marker – napsin A. However, this finding was not explored in detail. Napsin A (Novel aspartic proteinase of the pepsin family) is an enzyme involved in surfactant protein maturation, which is definitely indicated in type II pneumocytes and in the majority of lung adenocarcinomas.8 In the recent years, napsin A offers emerged as a useful and broadly utilized diagnostic marker, Rabbit Polyclonal to Cytochrome P450 1B1 which is helpful for confirming lung origin in carcinomas of unknown main and for distinguishing lung adenocarcinomas from other pulmonary neoplasms, such as squamous cell carcinoma and mesothelioma. 9-12 Prior to napsin A, the predominant marker of lung glandular differentiation has been TTF-1. However, TTF-1 isn’t just a marker of pneumocytes lineage, but it is also a putative regulator of neurogenesis, which is well known to be indicated in small cell carcinoma and LCNEC of various sites.13-15 This dual role of TTF-1 precludes its use like a marker of exocrine differentiation in lung tumors. Therefore, emergence of napsin A presents a new opportunity to assess exocrine differentiation in LCNEC. The literature on napsin A manifestation in LCNEC and additional lung neuroendocrine neoplasms is definitely relatively limited. Few available studies to day have focused primarily on napsin A manifestation in carcinoid tumors and small cell carcinomas, getting those tumors to be consistently napsin A-negative.12, 16, 17 To our knowledge, only two prior studies included large series of LCNECs in the analysis of napsin A manifestation, and reported Betanin manufacturer consistent absence of napsin A in those tumors.16, 18 This contrasts with the finding from your above two studies showing napsin A manifestation in some LCNECs with adeno-like molecular features.6, 14, 19 In addition, in our clinical practice, Betanin manufacturer we have experienced a number of instances with classical features of LCNEC, which showed convincing labeling for napsin A. The goal of this study was consequently to clarify these conflicting observations concerning napsin A manifestation in LCNECs. Here we statement on the analysis of napsin A along with TTF-1 manifestation in 112 LCNEC with detailed clinicopathologic and molecular characterization of napsin A-positive instances. For assessment, we analyzed napsin A manifestation in 177 carcinoids, 37 small cell carcinomas, and 60 lung adenocarcinomas. MATERIALS & METHODS Samples The study was performed with the approval of the Memorial Sloan Kettering Malignancy Center (New York, NY) Institutional Review Table. Napsin A manifestation was analyzed in a total of 112 LCNECs, of which 69 instances were represented in cells microarrays and 43 instances – in whole-tissue sections. The second option group of tumors was also included in our prior publication. 6 All instances with napsin A manifestation recognized in cells microarrays, were consequently analyzed using whole-tissue sections. Other analyzed lung neuroendocrine tumors included standard carcinoids (n=88), atypical carcinoids (n=89), and small cell carcinomas (n=37), which were studied in cells microarrays. Cells microarrays were constructed from medical resection specimens performed at our institution between 1992 and 2007. The tumors were sampled in triplicate using 2-mm cores from representative tumor areas. Like a control group, 60 consecutively-resected lung adenocarcinomas were analyzed in whole-tissue sections. Immunohistochemistry Immunohistochemistry was performed on a Ventana Finding XT automated stainer (Ventana Medical Systems, Tucson, AZ, USA). Tissue-microarrays were analyzed using napsin A polyclonal antibody (rabbit polyclonal antibody; Ventana Medical Systems, Tucson, AZ, USA) and TTF-1 (mouse monoclonal; 8G7G3/1; Dako, Carpinteria, CA, USA). Given the data on potential lack of specificity of polyclonal napsin A antibody,11, 20 all positive instances detected in cells microarrays with polyclonal antibody were rested in whole-tissue section using both polyclonal and monoclonal napsin A antibodies (mouse monoclonal; clone IP64; Leica Biosystems, Buffalo Grove, IL, USA). Percentage of napsin A-immunoreactive tumor cells and the intensity of staining (1+ = poor; 2+ = moderate; 3+ = strong) were recorded. Whole-tissue sections from all napsin Betanin manufacturer A-positive instances were additionally analyzed by immunohistochemistry.