title: Napsin-A, TTF-1, EGFR, and ALK Status Determination in Lung Primary and Metastatic Mucin-Producing Adenocarcinomas.
abstract: Pulmonary mucin-producing adenocarcinomas may be indistinguishable on conventional histology from a metastasis, as thyroid transcription factor-1 (TTF-1) expression often is lacking and KRAS mutations are widely present even in extrapulmonary sites. Few data have been reported on the diagnostic role of napsin-A and epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations in this challenging differential diagnosis. Seventy-seven surgically resected cases, including 53 primary and 24 metastatic tumors from different sites, were evaluated for napsin-A, TTF-1, and ALK by immunohistochemistry and for EGFR mutations by direct sequencing. Overall, napsin-A expression in primary lung mucin-producing adenocarcinomas was 36% (8% mucinous, 17% colloid, 87.5% solid, and 100% signet ring cell) and TTF-1 expression reached an overall figure of 42% (12.5% mucinous, 33% colloid, 87.5% solid, and 100% signet ring cell). Metastatic mucinous adenocarcinomas did not react with napsin-A or with TTF-1. All primary and metastatic tumors lacked EGFR mutations, while a single case of signet ring cell lung adenocarcinoma showed ALK expression and rearrangement at fluorescent in situ hybridization analysis. Napsin-A has a lower sensitivity compared with TTF-1 in primary mucin-producing adenocarcinomas of the lung. However, both antibodies have an absolute specificity, being always negative in metastatic mucinous adenocarcinomas. EGFR mutations and ALK translocation or expression are exceedingly rare in mucin-producing adenocarcinomas of the lung, resulting unnecessary as diagnostic tool in this setting.
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Azienda Arcispedale S. Maria Nuova/IRCCS, Reggio Emilia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
authors.affiliation: University of Turin, San Luigi Hospital, Orbassano, Turin, Italy luisella.righi@unito.it.
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Sartori
authors.affiliation: Azienda Arcispedale S. Maria Nuova/IRCCS, Reggio Emilia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisagni
authors.affiliation: Ramazzini Civic Hospital, Carpi, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Longo
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.affiliation: University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D000077548:Anaplastic Lymphoma Kinase; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human
keywords: EGFR; TTF-1; adenocarcinoma; immunohistochemistry; lung; metastasis; mucinous; napsin-A