J Korean Med Sci.  2010 Oct;25(10):1449-1455. 10.3346/jkms.2010.25.10.1449.

Expression of pRb, p53, p16 and Cyclin D1 and Their Clinical Implications in Urothelial Carcinoma

• Lee K
• Jung ES
• Choi YJ
• Lee KY
• Lee A

• KMID: 2157848
• DOI: http://doi.org/10.3346/jkms.2010.25.10.1449

Abstract

The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.

Keyword

p53; pRb; p16; Cyclin D1; Urothelial Carcinoma

MeSH Terms

Adult
Aged
Aged, 80 and over
Carcinoma, Transitional Cell/*metabolism/mortality/pathology
Cyclin D1/*metabolism
Cyclin-Dependent Kinase Inhibitor p16/*metabolism
Female
Humans
Immunohistochemistry
Lymphatic Metastasis
Male
Middle Aged
Multivariate Analysis
Neoplasm Staging
Prognosis
Recurrence
Retinoblastoma Protein/*metabolism
Survival Rate
Tumor Suppressor Protein p53/*metabolism
Urinary Bladder Neoplasms/*metabolism/mortality/pathology

Figure

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  Fig. 1 Immunohistochemical expression. (A, B) pRb strong homogenous positive and negative (pRb, ×400), (C, D) p16 homogenous positive and negative (p16, ×400), (E) p53 positive (p53, ×400), (F) cyclin D1 positive (Cyclin D1, ×400).

• 

  Fig. 2 Overall survival curves according to pRb status (P value from log rank test).

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  Fig. 3 Overall survival curves according to combined p53 and pRb status (P value from log rank test).

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  Fig. 4 Overall survival curves according to the number of altered markers (P value from log rank test).

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