title: Expression of EGFR and molecules downstream to PI3K/Akt, Raf-1-MEK-1-MAP (Erk1/2), and JAK (STAT3) pathways in invasive lung adenocarcinomas resected at a single institution.
abstract: Therapies targeting EGFR are effective in treating tumors that harbor molecular alterations; however, there is heterogeneity in long-term response to these therapies. We retrospectively analyzed protein expression of EGFR, Stat3, phospho-Akt, and phospho-Erk1/2 by immunohistochemistry in a series of resected cases from a single institution, correlated with clinicopathological variables. There were 96 patients, with the majority of cases being of low stage tumors (17 pT1a, 23 pT1b, 30 pT2a, and 18 pT2b). Histologic subtypes were 45 acinar predominant, 2 cribriform, 25 solid, 7 papillary, 11 lepidic, and 4 mucinous tumors. The EGFR score was higher in tumors with vascular invasion (P = 0.013), in solid and cribriform acinar histology, and in high stage tumors (P = 0.006 and P = 0.01). EGFR was more likely overexpressed in solid compared to lepidic tumors (P = 0.02). Acinar tumors had the highest rate of ERK1/2 positivity (19%). There was a strong correlation among positivity for ERCC1 and other markers, including STAT3 (P = 0.003), Akt (P = 0.02), and ERK1/ERK2 (P = 0.0005). Expression of molecules downstream to EGFR varied from 12% to 31% of tumors; however, the expression did not directly correlate to EGFR expression, which may suggest activation of the cascades through different pathways. The correlation of protein expression and the new lung adenocarcinoma classification may help in the understanding of activated pathways of each tumor type, which may act in the oncogenesis and drug resistance of these tumors.
authors.affiliation: Department of Investigative Pathology, Argos Laboratories, 60175-047 Fortaleza, CE, Brazil.
authors.forename: Alba Fabiola
authors.initials: AF
authors.lastname: Torres
authors.affiliation: Department of Investigative Pathology, Argos Laboratories, 60175-047 Fortaleza, CE, Brazil.
authors.forename: Cleto
authors.initials: C
authors.lastname: Nogueira
authors.affiliation: Department of Investigative Pathology, Argos Laboratories, 60175-047 Fortaleza, CE, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Magalhaes
authors.affiliation: Department of Investigative Pathology, Argos Laboratories, 60175-047 Fortaleza, CE, Brazil.
authors.forename: Igor Santos
authors.initials: IS
authors.lastname: Costa
authors.affiliation: Department of Pathology, Messejana Heart and Lung Hospital, Rua Frei Cirilo 4290, 60846-190 Fortaleza, CE, Brazil.
authors.forename: Alessa
authors.initials: A
authors.lastname: Aragao
authors.affiliation: Department of Thoracic Surgery, Messejana Heart and Lung Hospital, 60846-190 Fortaleza, CE, Brazil.
authors.forename: Antero
authors.initials: A
authors.lastname: Gomes Neto
authors.affiliation: Department of Pulmonology, Messejana Heart and Lung Hospital, 60846-190 Fortaleza, CE, Brazil.
authors.forename: Filadelfia
authors.initials: F
authors.lastname: Martins
authors.affiliation: Department of Investigative Pathology, Argos Laboratories, 60175-047 Fortaleza, CE, Brazil ; Department of Pathology, Messejana Heart and Lung Hospital, Rua Frei Cirilo 4290, 60846-190 Fortaleza, CE, Brazil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Tavora
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000145:classification / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt