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


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).


CONCLUSIONS
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.
Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
John P
JP
Sfakianos
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
Lan
L
Lin Gellert
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.
Alexandra
A
Maschino
Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
Geoffrey T
GT
Gotto
Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
Philip H
PH
Kim
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.
Hikmat
H
Al-Ahmadie
Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: bochnerb@mskcc.org.
Bernard H
BH
Bochner
D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015331:Cohort Studies; D015653:Cystectomy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009163:Mycobacterium bovis / Q000737:chemistry; D009364:Neoplasm Recurrence, Local; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Bladder cancer; Carcinoma in situ; PTEN