title: Expression of mTORC1/2-related proteins in primary and brain metastatic lung adenocarcinoma.
abstract: Brain metastases (BMs) are common complications of adenocarcinomas (ADCs) of the lung and are associated with a poor prognosis. Although an increasing amount of data indicates that dysregulated activity of mammalian target of rapamycin (mTOR) can influence the metastatic potential of various tumors, the role of mTOR complexes in the development of BMs from ADCs of the lung is largely unknown. To estimate mTOR activity, we studied the expression of mTOR-related proteins (mTORC1: p-mTOR, p-S6; mTORC2: p-mTOR, Rictor) in primary (n=67) and brain metastatic (n=67) lung ADCs, including 15 paired tissue samples, using immunohistochemistry and tissue microarrays. Correlation with clinicopathological parameters was also analyzed. Increased p-mTOR, p-S6, and Rictor expressions were observed in 34%, 33%, and 37% of primary ADCs and in 79%, 70%, and 66% of BMs, respectively. Expression of these markers was significantly higher in BMs as compared with primary carcinomas (P<.0001, P<.0001, P<.001). Rictor expression was significantly higher in primary ADCs of the paired cases with BMs as compared with primary ADCs without BMs (67% versus 28%; P<.01). No other statistically significant correlations were found between mTOR activity and clinicopathological parameters. The increased mTORC1/C2 activity in a subset of pulmonary ADCs and the higher incidence of increased mTORC1/C2 activity in BMs suggest that the immunohistochemistry panel for characterizing mTOR activity and its potential predictive and prognostic role warrants further investigations.
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Krencz
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary; Tumor Progression Research Group Joint Research Organization of Hungarian Academy of Sciences and Semmelweis University, 1117 Budapest, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Sebestyén
authors.affiliation: Department of Pulmonology, Semmelweis University, 1125 Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Fábián
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Márk
authors.affiliation: Department of Tumor Biology, National Korányi Institute of TB and Pulmonology, 1121 Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Moldvay
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: András
authors.initials: A
authors.lastname: Khoor
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Kopper
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary. Electronic address: papay.judit@med.semmelweis-univ.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Pápay
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000556:secondary / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000556:secondary / Q000601:surgery; D002352:Carrier Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D006814:Hungary; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000032:analysis*; D010766:Phosphorylation; D011379:Prognosis; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D019893:Ribosomal Protein S6 Kinases / Q000032:analysis; D058570:TOR Serine-Threonine Kinases / Q000032:analysis*; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D046912:Multiprotein Complexes; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases
keywords: Brain metastasis; Immunohistochemistry; Lung adenocarcinoma; mTORC1; mTORC2