Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of urothelial carcinoma of the urinary bladder.
Plasmacytoid urothelial carcinoma is a rare but aggressive variant of bladder cancer with no clear therapeutic guidelines. Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been linked to oncogenesis in conventional bladder cancer. Several antineoplastic agents targeting mTOR pathway are currently available. This study assesses mTOR pathway status as well as c-myc and p27 expression. We retrieved 19 archival cases of plasmacytoid urothelial carcinoma from two institutions. Whole tissue sections were evaluated for immunoexpression of phosphatase and tensin homolog (PTEN), phosphorylated mTOR, phosphorylated protein kinase B (AKT), phosphorylated S6, c-myc, and p27. We evaluated intensity (0 to 3+) and extent (0%-100%) of expression for all markers. An H score was calculated as the sum of products of intensity and extent for each marker and used during analysis. In addition, PTEN loss was defined as absence of expression in >10% of tumor cells. We encountered PTEN loss in 28%. Higher H score for nuclear phosphorylated AKT and a lower H score for phosphorylated S6 was encountered in muscle invasive tumors compared to non-muscle invasive tumors (P = .007 and P = .009, respectively). Although a trend for negative prognostic impact on overall survival for higher phosphorylated mTOR expression was noted (P = .051), markers expression levels failed to predict survival in our cohort. We found dysregulation of mTOR pathway members in urinary bladder plasmacytoid urothelial carcinoma, suggesting that the use of mTOR pathway inhibitors might be beneficial for patients with this aggressive tumor.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Nilda D
ND
Gonzalez-Roibon
Alcides
A
Chaux
Turki
T
Al-Hussain
Adeboye O
AO
Osunkoya
Stephania Martins
SM
Bezerra
Jessica
J
Hicks
Jonathan I
JI
Epstein
George J
GJ
Netto
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005845:Georgia / Q000453:epidemiology; D006801:Humans; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human