Skip to main content
Erschienen in: Virchows Archiv 6/2018

30.04.2018 | Original Article

Pathologic significance of AKT, mTOR, and GSK3β proteins in oral squamous cell carcinoma-affected patients

verfasst von: Flávia Sayuri Matsuo, Marília Ferreira Andrade, Adriano Mota Loyola, Sindeval José da Silva, Marcelo José Barbosa Silva, Sérgio Vitorino Cardoso, Paulo Rogério de Faria

Erschienen in: Virchows Archiv | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3β activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3β proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1Thr308, pAKTSer473, GSK3β, pGSK3βSer9, and pmTORSer2448 was analyzed by immunohistochemistry. The mean expression of GSK3β, pGSK3βSer9, total AKT, and pmTOR2448 was always higher in the OSCC tissues than that in the controls. A positive correlation was also found among these proteins. Total AKT, pmTORSer2448, and pGSK3βSer9 expression was significantly higher in the PNM and PM groups than that in the control group. However, only GSK3β expression was significantly higher in the PM group compared with the PNM group. High expression levels of GSK3β and pGSK3βSer9 were significantly associated with CLN metastasis, but only GSK3β remained an independent predictor of CLN metastasis. pGSK3βSer9 and CLN metastasis were associated with a poor prognosis, but only the latter remained an independent prognostic parameter. Kaplan-Meier survival curves showed that pGSK3βSer9 and CLN metastasis were significantly related to reduced survival rates. These results suggest that AKT and mTOR proteins are involved in OSCC biology and that GSK3β itself may drive CLN metastatic spread of OSCC cells.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
4.
Zurück zum Zitat Biazevic MG, Castellanos RA, Antunes JL, Michel-Crosato E (2006) Trends in oral cancer mortality in the city of Sao Paulo, Brazil, 1980-2002. Cad Saude Publica 22(10):2105–2114CrossRefPubMed Biazevic MG, Castellanos RA, Antunes JL, Michel-Crosato E (2006) Trends in oral cancer mortality in the city of Sao Paulo, Brazil, 1980-2002. Cad Saude Publica 22(10):2105–2114CrossRefPubMed
5.
Zurück zum Zitat Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB (1994) Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer 73(1):187–190CrossRefPubMed Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB (1994) Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer 73(1):187–190CrossRefPubMed
13.
Zurück zum Zitat Fenic I, Steger K, Gruber C, Arens C, Woenckhaus J (2007) Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma. Oncol Rep 18(1):253–259PubMed Fenic I, Steger K, Gruber C, Arens C, Woenckhaus J (2007) Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma. Oncol Rep 18(1):253–259PubMed
21.
Zurück zum Zitat Moral M, Paramio JM (2008) Akt pathway as a target for therapeutic intervention in HNSCC. Histol Histopathol 23(10):1269–1278PubMed Moral M, Paramio JM (2008) Akt pathway as a target for therapeutic intervention in HNSCC. Histol Histopathol 23(10):1269–1278PubMed
23.
Zurück zum Zitat Mendonca DF, Chammas R, Liu FT, Nonogaki S, Cardoso SV, Loyola AM, de Faria PR (2012) The inactive form of glycogen synthase kinase-3beta is associated with the development of carcinomas in galectin-3 wild-type mice, but not in galectin-3-deficient mice. Int J Clin Exp Pathol 5(6):547–554PubMedPubMedCentral Mendonca DF, Chammas R, Liu FT, Nonogaki S, Cardoso SV, Loyola AM, de Faria PR (2012) The inactive form of glycogen synthase kinase-3beta is associated with the development of carcinomas in galectin-3 wild-type mice, but not in galectin-3-deficient mice. Int J Clin Exp Pathol 5(6):547–554PubMedPubMedCentral
26.
29.
Zurück zum Zitat Cardesa A, Gale N, Nadal A, Zidar N (2005) Tumors of the hypopharynx, larynx and trachea. In: Barnes L, Eveson JW, Reichart P, Sidransky D (eds) World Health Organization classification of tumors. Pathology and genetics of head and neck tumors. IARC, Lyon, pp 118–121 Cardesa A, Gale N, Nadal A, Zidar N (2005) Tumors of the hypopharynx, larynx and trachea. In: Barnes L, Eveson JW, Reichart P, Sidransky D (eds) World Health Organization classification of tumors. Pathology and genetics of head and neck tumors. IARC, Lyon, pp 118–121
30.
Zurück zum Zitat Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4(7):844–847CrossRefPubMed Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4(7):844–847CrossRefPubMed
31.
Zurück zum Zitat Detre S, Saclani Jotti G, Dowsett M (1995) A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48(9):876–878CrossRefPubMedPubMedCentral Detre S, Saclani Jotti G, Dowsett M (1995) A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48(9):876–878CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Cortesina G, Martone T (2006) Molecular metastases markers in head and neck squamous cell carcinoma: review of the literature. Acta Otorhinolaryngol Ital 26(6):317–325PubMedPubMedCentral Cortesina G, Martone T (2006) Molecular metastases markers in head and neck squamous cell carcinoma: review of the literature. Acta Otorhinolaryngol Ital 26(6):317–325PubMedPubMedCentral
Metadaten
Titel
Pathologic significance of AKT, mTOR, and GSK3β proteins in oral squamous cell carcinoma-affected patients
verfasst von
Flávia Sayuri Matsuo
Marília Ferreira Andrade
Adriano Mota Loyola
Sindeval José da Silva
Marcelo José Barbosa Silva
Sérgio Vitorino Cardoso
Paulo Rogério de Faria
Publikationsdatum
30.04.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 6/2018
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-018-2318-0

Weitere Artikel der Ausgabe 6/2018

Virchows Archiv 6/2018 Zur Ausgabe

Neu im Fachgebiet Pathologie