Cyclin-dependent kinase inhibitor P27(KIP1) is expressed preferentially in early stages of urothelial carcinoma.
OBJECTIVE
To evaluate the expression of p27(KIP1) and p21(CIP1) and the prognostic values of both markers in urothelial carcinoma. The expression of the cyclin-dependent kinase inhibitor p27(KIP1) characterizes early-stage and well-differentiated carcinomas of the colon, breast, and prostate and is associated with an improved prognosis. In urothelial carcinoma, its expression has not been as well investigated. Another cyclin-dependent kinase inhibitor, p21(CIP1), is expressed in early-stage bladder tumors, but published data on its prognostic value are contradictory.


METHODS
Expression of p27(KIP1) and p21(CIP1) was analyzed by immunohistochemistry in 114 urothelial carcinoma specimens from 77 patients. The Ki67 index was determined as an indicator of cell proliferation. The expression of the markers was correlated with tumor recurrence and progression during an average follow-up period of 3.9 years.


RESULTS
Expression of p27(KIP1) was significantly more frequent in superficial than in muscle-invasive tumors (chi-square test, P = 0.012; Fisher's exact test, P = 0.014). Although similar overall, the expression pattern of p21(CIP1) did not match on a tumor-by-tumor basis. No correlation was seen with the Ki67 index. Patients with tumors displaying strong positive staining for p27(KIP1) or p21(CIP1) had fewer recurrences and progression events, but the difference was not statistically significant. Instead, a Ki67 index of less than 10% was significantly (P = 0.0335) related to a lack of recurrence.


CONCLUSIONS
Neither p27(KIP1) nor p21(CIP1) appear to be good predictors of tumor progression in urothelial carcinoma, even though their expression is strongly decreased in muscle-invasive tumors.
Franke
K H
KH
Department of Urology, Heinrich-Heine-University, Düsseldorf, Germany.
Miklosi
M
M
Goebell
P
P
Clasen
S
S
Steinhoff
C
C
Anastasiadis
A G
AG
Gerharz
C
C
Schulz
W A
WA
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology; D002278:Carcinoma in Situ; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D025521:Tumor Suppressor Proteins; D014571:Urologic Neoplasms / Q000737:chemistry* / Q000473:pathology; D019459:Urothelium / Q000737:chemistry*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases