title: Does Immunohistochemistry Represent a Robust Alternative Technique in Determining Drugable Predictive Gene Alterations in Non-Small Cell Lung Cancer?
abstract: Immunohistochemistry (IHC) is a widely-tested, low-cost and rapid ancillary technique available in all laboratories of pathology. This method is generally used for diagnostic purposes, but several studies have investigated the sensitivity and specificity of different immunohistochemical antibodies as a surrogate test in the determination of predictive biomarkers in non-small cell lung cancer (NSCLC), particularly for Epidermal Growth Factor Receptor (EGFR) gene mutations, Anaplastic Lymphoma Kinase (ALK) gene and ROS1 rearrangements. In this review, a critical examination of the works comparing the consistency of IHC expression and conventional molecular techniques to identify genetic alterations with predictive value in NSCLC is discussed. Summarizing, data on sensitivity and specificity of antibodies against ALK and ROS1 are very consistent and time has come to trust in IHC at least as a cost-effective screening tool to identify patients with rearranged tumors in clinical practice. On the other hand, mutant-specific antibodies against EGFR demonstrate a good specificity but a lowto- fair sensitivity, raising some cautions on their employment as robust predictive biomarkers. A brief comment on preliminary experiences with antibodies against BRAF, RET, HER2 and c-MET is also included.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Operative Unit of Anatomic Pathology, Arcispedale Santa Maria Nuova/ I.R.C.C.S, Viale Risorgimento, 80, 42123 Reggio Emilia, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Ragazzi
authors.forename: Ione
authors.initials: I
authors.lastname: Tamagnini
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mengoli
authors.forename: Giada
authors.initials: G
authors.lastname: Vincenzi
authors.forename: Fausto
authors.initials: F
authors.lastname: Barbieri
authors.forename: Silvia
authors.initials: S
authors.lastname: Piccioli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisagni
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vavala
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Francesco
authors.initials: F
authors.lastname: Gelsomino
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics / Q000379:methods*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases