Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of urothelial carcinoma of the urinary bladder

Nilda D. Gonzalez-Roibon, Alcides Chaux, Turki Al-Hussain, Adeboye O. Osunkoya, Stephania Martins Bezerra, Jessica Hicks, Jonathan I. Epstein, George J. Netto

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)612-622
Number of pages11
JournalHuman pathology
Issue number4
StatePublished - Apr 1 2013



  • Bladder
  • Mammalian target of rapamycin
  • PTEN
  • Plasmacytoid urothelial carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Gonzalez-Roibon, N. D., Chaux, A., Al-Hussain, T., Osunkoya, A. O., Bezerra, S. M., Hicks, J., Epstein, J. I., & Netto, G. J. (2013). Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of urothelial carcinoma of the urinary bladder. Human pathology, 44(4), 612-622. https://doi.org/10.1016/j.humpath.2012.07.009