Expression of mTORC1/2-related proteins in primary and brain metastatic lung adenocarcinoma

Ildikó Krencz, A. Sebestyén, Katalin Fábián, Ágnes Márk, Judit Moldvay, András Khoor, L. Kópper, Judit Pápay

Research output: Article

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)66-73
Number of pages8
JournalHuman Pathology
Volume62
DOIs
Publication statusPublished - ápr. 1 2017

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Sirolimus
Neoplasm Metastasis
Brain
Proteins
S 6
Adenocarcinoma
Immunohistochemistry
TOR Serine-Threonine Kinases
Adenocarcinoma of lung
mechanistic target of rapamycin complex 1
Carcinoma
Incidence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expression of mTORC1/2-related proteins in primary and brain metastatic lung adenocarcinoma. / Krencz, Ildikó; Sebestyén, A.; Fábián, Katalin; Márk, Ágnes; Moldvay, Judit; Khoor, András; Kópper, L.; Pápay, Judit.

In: Human Pathology, Vol. 62, 01.04.2017, p. 66-73.

Research output: Article

Krencz, Ildikó ; Sebestyén, A. ; Fábián, Katalin ; Márk, Ágnes ; Moldvay, Judit ; Khoor, András ; Kópper, L. ; Pápay, Judit. / Expression of mTORC1/2-related proteins in primary and brain metastatic lung adenocarcinoma. In: Human Pathology. 2017 ; Vol. 62. pp. 66-73.
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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.",
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AU - Krencz, Ildikó

AU - Sebestyén, A.

AU - Fábián, Katalin

AU - Márk, Ágnes

AU - Moldvay, Judit

AU - Khoor, András

AU - Kópper, L.

AU - Pápay, Judit

PY - 2017/4/1

Y1 - 2017/4/1

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AB - 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.

KW - Brain metastasis

KW - Immunohistochemistry

KW - Lung adenocarcinoma

KW - mTORC1

KW - mTORC2

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