title: ALK rearrangement in specific subtypes of lung adenocarcinoma: immunophenotypic and morphological features.
abstract: Lung adenocarcinomas are characterized by a variety of genetic and epigenetic changes that lead to activation of specific signaling pathways. This allowed the classification of lung adenocarcinomas according to genetic alterations and the clinical development of novel anticancer agents that affect the activity of specific oncoproteins. In such a context, chromosomal rearrangements that cause constitutive activation of ALK gene define a category of lung adenocarcinomas that is amenable to targeted therapy with ALK inhibitors. Thus, a major issue of current research is to define the morphological and immunophenotypic features of lung ALK-rearranged adenocarcinomas to improve the selection of tumors suitable for molecular genotyping. ALK status was determined, by immunohistochemistry and fluorescence in situ hybridization, in 94 surgically resected lung adenocarcinomas and correlated with histomorphological parameters. Indeed, ALK rearrangement was observed in 10/94 (11%) lung adenocarcinomas and enriched in tumors with a predominant mucinous (46%; p < 0.05) and solid (29%; p < 0.05) pattern. By contrast, it was lacking or sporadically observed in lung adenocarcinomas with predominant acinar, papillary or lepidic pattern. Moreover, the presence of signet-ring cells was predominantly observed in ALK-rearranged tumors (47%; p < 0.05). These data suggest that ALK rearrangement is associated with specific and distinct clinical-pathological characters compared to other genotypes. Thus, the knowledge of these characteristics can improve the diagnostic accuracy and lead to a better understanding of the behavior of ALK-rearranged NSCLC.
authors.affiliation: Laboratory of Clinical Research and Advanced Diagnostics, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy. luciana.possidente@crob.it.
authors.forename: Luciana
authors.initials: L
authors.lastname: Possidente
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy.|Medical Oncology, Department of Medical and Surgical Sciences, University of Foggia, 71100, Foggia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Landriscina
authors.affiliation: Pathology Unit, IRCCS, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Patitucci
authors.affiliation: Pathology Unit, IRCCS, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Borgia
authors.affiliation: Pathology Unit, IRCCS, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Lalinga
authors.affiliation: Pathology Unit, IRCCS, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vita
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C504003:TTF1 protein, human; D014157:Transcription Factors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK rearrangement; FISH analysis; Histomorphological parameters; Non-small cell lung adenocarcinomas