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 language | English (US) |
|---|---|
| Pages (from-to) | 2668-2676 |
| Number of pages | 9 |
| Journal | Human Pathology |
| Volume | 44 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2013 |
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Keywords
- Mammalian target of rapamycin
- mTOR pathway
- Prognosis
- Upper tract
- Urothelial carcinoma
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma
AU - Munari, Enrico
AU - Fujita, Kazutoshi
AU - Faraj, Sheila
AU - Chaux, Alcides
AU - Gonzalez-Roibon, Nilda
AU - Hicks, Jessica
AU - Meeker, Alan Keith
AU - Nonomura, Norio
AU - Netto, George J.
PY - 2013/12
Y1 - 2013/12
N2 - 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
AB - 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
KW - Mammalian target of rapamycin
KW - mTOR pathway
KW - Prognosis
KW - Upper tract
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84888036240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888036240&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2013.07.008
DO - 10.1016/j.humpath.2013.07.008
M3 - Article
C2 - 24074531
AN - SCOPUS:84888036240
VL - 44
SP - 2668
EP - 2676
JO - Human Pathology
JF - Human Pathology
SN - 0046-8177
IS - 12
ER -