Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma

Enrico Munari, Kazutoshi Fujita, Sheila Faraj, Alcides Chaux, Nilda Gonzalez-Roibon, Jessica Hicks, Alan Keith Meeker, Norio Nonomura, George J. Netto

Research output: Contribution to journalArticle

Abstract

Upper tract urothelial carcinoma (UTUC) accounts for 5% to 10% of all urothelial carcinomas. Despite many shared features, key clinical and molecular genetic differences between upper tract and bladder urothelial carcinomas are becoming apparent. We have previously demonstrated alterations of mammalian target of rapamycin (mTOR) pathway in bladder carcinoma with a potential impact on biological behavior. In the current study, we evaluated the expression status and prognostic significance of mTOR pathway members in UTUC. Archival formalin-fixed and paraffin-embedded tissues from 99 primary UTUCs were retrieved from one of the authors' institution. Tissue microarrays were constructed with triplicate tumor samples and paired nonneoplastic urothelium. Tissue microarrays were analyzed using immunohistochemistry for mTOR pathway members: PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, and related markers p27 and c-MYC; correlation with clinicopathologic parameters and outcome was performed. We found significantly lower expression of PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, p27, and c-MYC in UTUC compared with paired benign urothelium (P

Original languageEnglish (US)
Pages (from-to)2668-2676
Number of pages9
JournalHuman Pathology
Volume44
Issue number12
DOIs
StatePublished - Dec 2013

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Sirolimus
Carcinoma
S 6
Urothelium
Urinary Bladder
Paraffin
Formaldehyde
Molecular Biology
Immunohistochemistry
Neoplasms

Keywords

  • Mammalian target of rapamycin
  • mTOR pathway
  • Prognosis
  • Upper tract
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Munari, E., Fujita, K., Faraj, S., Chaux, A., Gonzalez-Roibon, N., Hicks, J., ... Netto, G. J. (2013). Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma. Human Pathology, 44(12), 2668-2676. https://doi.org/10.1016/j.humpath.2013.07.008

Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma. / Munari, Enrico; Fujita, Kazutoshi; Faraj, Sheila; Chaux, Alcides; Gonzalez-Roibon, Nilda; Hicks, Jessica; Meeker, Alan Keith; Nonomura, Norio; Netto, George J.

In: Human Pathology, Vol. 44, No. 12, 12.2013, p. 2668-2676.

Research output: Contribution to journalArticle

Munari, E, Fujita, K, Faraj, S, Chaux, A, Gonzalez-Roibon, N, Hicks, J, Meeker, AK, Nonomura, N & Netto, GJ 2013, 'Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma', Human Pathology, vol. 44, no. 12, pp. 2668-2676. https://doi.org/10.1016/j.humpath.2013.07.008
Munari E, Fujita K, Faraj S, Chaux A, Gonzalez-Roibon N, Hicks J et al. Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma. Human Pathology. 2013 Dec;44(12):2668-2676. https://doi.org/10.1016/j.humpath.2013.07.008
Munari, Enrico ; Fujita, Kazutoshi ; Faraj, Sheila ; Chaux, Alcides ; Gonzalez-Roibon, Nilda ; Hicks, Jessica ; Meeker, Alan Keith ; Nonomura, Norio ; Netto, George J. / Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma. In: Human Pathology. 2013 ; Vol. 44, No. 12. pp. 2668-2676.
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