title: Histomolecular profiling of pleomorphic, spindle cell, and giant cell carcinoma of the lung for targeted therapies.
abstract: In pleomorphic, spindle cell, and giant cell carcinoma (PSCGC) of the lung, we wondered if an integrated diagnosis including morphological and immunohistochemical features could be related to molecular status. We performed immunohistochemistry on 35 PSCGCs against TTF1, napsin A, p40, ALK, ROS1, and c-MET. Mutational status regarding EGFR, KRAS, BRAF, HER2, and PIK3CA genes was established. Of 18 PSCGCs with adenocarcinomatous or "undifferentiated" carcinoma differentiation, 8 were mutated for EGFR (n = 1), KRAS (n = 2), BRAF (n = 1), HER2 (n = 3), and PIK3CA (n = 1). No PSCGC (0/4) with only squamous cell or adenosquamous (0/2) differentiation was mutated. c-MET overexpression was only seen in PSCGC with adenocarcinomatous or undifferentiated component (n = 5) without squamous cell component. ROS1 and ALK were negative. The presence of a "targetable mutation" was correlated to the presence of morphological or immunohistochemical adenocarcinomatous differentiation (P = .0137). Integrated diagnosis of an adenocarcinomatous component in PSCGC could be associated with the presence of targetable gene mutation. Because only PSCGC with adenocarcinomatous or undifferentiated carcinoma harbors mutations, whereas PSCGC with only squamous or adenosquamous differentiation does not in our study, this might represent a prescreening for patients with PSCGC to be tested for molecular targets. Our results emphasize that careful morphological examination and the use of immunohistochemistry might be useful for the selection of PSCGC tested for a mutational target.
authors.affiliation: Pathology Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France. Electronic address: fabien.forest@chu-st-etienne.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Forest
authors.affiliation: Pathology Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Yvorel
authors.affiliation: Pathology Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France.
authors.forename: Georgia
authors.initials: G
authors.lastname: Karpathiou
authors.affiliation: Pathology Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Stachowicz
authors.affiliation: Pneumology Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vergnon
authors.affiliation: Lucien Neuwirth Cancer Institute, 42270 Saint Priest en Jarez, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fournel
authors.affiliation: Thoracic Surgery Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tiffet
authors.affiliation: Public Health and Medical Informatics Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Trombert
authors.affiliation: Pathology Department, Saint-Etienne University Hospital, North Hospital, 42055 Saint Étienne CEDEX 2, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Péoc'h
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D018196:Carcinoma, Adenosquamous / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018286:Carcinoma, Giant Cell / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: Lung neoplasms; Molecular targeted therapy; Sarcomatoid carcinoma; TTF1 protein; p40 protein