The role of PTEN tumor suppressor pathway staining in carcinoma in situ of the bladder

John P. Sfakianos, Lan Lin Gellert, Alexandra Maschino, Geoffrey T. Gotto, Philip H. Kim, Hikmat Al-Ahmadie, Bernard H. Bochner

Research output: Contribution to journalArticlepeer-review


Objectives: The PI3k/Akt pathway has been associated with the development and progression of bladder tumors, with most studies focused on papillary or muscle-invasive tumors. We sought to characterize the expression patterns of the PI3K/Akt pathway in a large cohort of high-risk preinvasive carcinoma in situ (CIS) tumors of the bladder. Our goal was to understand whether PI3K/Akt pathway alterations associated with CIS resemble early- or late-stage bladder cancers. Material and methods: We evaluated tissue specimens from 97 patients with CIS of the bladder, of which 14 had a concomitant papillary tumor. All patients were treated with intravesical bacillus Calmette-Guerin. All specimens were evaluated for PTEN, p-AKT, and p-S6 immunoreactivity. Markers were evaluated for percentage and intensity of staining and were scored using a 0 to 3+grading system. Results: PTEN staining was noted as least intense in 67% of tumor specimens and 22% of normal urothelium. P-Akt and p-S6 had intense staining in 77% and 90% of tumor specimens vs. 44% and 68% in normal tissue, respectively. Low-intensity staining for PTEN at 12 months correlated with higher recurrence risk (P = 0.026). Conclusion: We describe a large cohort of CIS bladder tumors with decreased staining intensity of PTEN and increased staining intensity of p-AKT and p-S6, similar to high-grade and high-stage papillary tumors. Low-intensity staining of PTEN at 12 months was associated with an increased risk of recurrence.

Original languageEnglish (US)
Pages (from-to)657-662
Number of pages6
JournalUrologic Oncology: Seminars and Original Investigations
Issue number5
StatePublished - Jul 2014


  • Bladder cancer
  • Carcinoma in situ
  • PTEN

ASJC Scopus subject areas

  • Oncology
  • Urology

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