The role of PTEN tumor suppressor pathway staining in carcinoma in situ of the bladder11Funding: Supported by the Sidney Kimmel Center for Prostate and Urologic Cancer and the Michael and Zea Wiener Foundation. Dr Sfakianos is a research fellow in urologic oncology supported by NIH T32-CA82088.

Abstract

Summary Objectives The PI3k/Akt pathway has been associated with 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 pre-invasive carcinoma in situ tumors of the bladder. Or goal was to understand whether PI3K/Akt pathway alterations associated with CIS resemble earlier or later stage bladder cancers. Material and Methods We evaluated tissue specimens from 97 patients with carcinoma in situ of the bladder, of which 14 had a concomitant papillary tumor. All patients were treated with intravesical BCG. All specimens were characterized for PTEN, p-AKT, and p-S6 immunoreactivity. Markers where evaluated for percentage and intensity of staining and were scored using a 0-3+ grading system. Results PTEN staining was noted as least intense in 67% of tumor specimens and 22% of normal urothelium. PAkt and p-S6 had intense staining in 77% and 90% of tumor specimens versus 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 carcinoma in situ bladder tumors with decreased staining intensity of PTEN and increased staining intensity of p-AKT and p-S6, similar to high grade and stage papillary tumors. Low intensity staining of PTEN at 12 months was associated with an increased risk of recurrence.

Precise definition of PTEN C-terminal epitopes and its implications in clinical oncology

“…Negative immunostaining was detected with all anti-PTEN mAb in a variable number of prostate or urothelial bladder samples positive for FISH analysis (Table 2, Table S1), suggesting the frequent loss of PTEN protein expression in these tumor types without deletion of the PTEN gene, in agreement with previous observations by others. 17,71,72 Sensitivity of the anti-PTEN mAb was tested by immunoblot using decreasing amounts of cell lysates containing ectopically expressed recombinant PTEN from transfected COS-7 cells. In these assays, the SP218, 6H2.1, and Y184A mAb displayed the higher sensitivity to detect PTEN (Fig.…”

Long Noncoding RNA GATA3-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Suppression of PTEN, CDKN1A, and TP53

“…To investigate the molecular mechanisms underlying the GATA3-AS1-mediated increase in HCC cell proliferation and metastasis, the expression levels of tumor-suppressive genes that play inhibitory roles in HCC progression were evaluated by RT-qPCR, including phosphatase and tensin homolog (PTEN) [21], cyclin-dependent kinase inhibitor 1A (CDKN1A) [22], and tumor protein p53 (TP53) [23]. As shown in Figures 6(a) and 6(b), GATA3-AS1 knockdown resulted in upregulation of PTEN, CDKN1A, and TP53 in Hep3B and HCCLM3 cells ( P < 0.05), while restoration of GATA3-AS1 notably decreased PTEN, CDKN1A and TP53 expression (Figures 6(c) and 6(d), P < 0.05).…”

Copy number variations of circulating, cell-free DNA in urothelial carcinoma of the bladder patients treated with radical cystectomy: a prospective study

“…In respect to our data, the majority of CNV were located in oncogenes and tumor suppressor genes, including CDH1, ZFHX3, RIPK2 and PTEN. These genes play a major role in cancer progression in various malignancies, including bladder cancer [ 21 – 24 ]. For the first time, our findings suggest that CNV in these genes may be of particular relevance for the understanding of the UCB biology.…”