Molecular genetic alterations in superficial and locally advanced human bladder cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 51; no. 19; pp. 5405 - 5409
• Main Authors: PRESTI, J. C, REUTER, V. E, GALAN, T, FAIR, W. R, CORDON-CARDO, C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.1991
• Subjects: Biological and medical sciences; Blotting, Southern; carcinoma; Chromosome Deletion; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 18; Chromosomes, Human, Pair 3; DNA - analysis; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Medical sciences; Neoplasm Invasiveness; Neoplasm Staging; Nephrology. Urinary tract diseases; Polymorphism, Restriction Fragment Length; restriction fragment length polymorphism; retinoblastoma; Retinoblastoma Protein - biosynthesis; Tumors of the urinary system; urinary bladder; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary tract. Prostate gland; Chromosomal aberration; Histological grading; Human; Immunohistochemistry; Urinary system disease; Pathogenesis; Partial deletion; Abnormal E18 chromosome; Abnormal A3 chromosome; Malignant tumor; Suppressor gene; Pathology; Clinical stage; Restriction fragment length polymorphism; Urinary bladder; Abnormal chromosome; Abnormal C11 chromosome; Abnormal D13 chromosome; Abnormal E17 chromosome
• ISSN: 0008-5472; 1538-7445

We attempted to define the role of tumor suppressor genes in the pathogenesis of human bladder cancer through a combined molecular genetic and immunohistochemical approach. Thirty-four bladder tumors (1 Pis, 6 Pa, 5 P1, 3 P3a, 18 P3b, 1 P4; 8 low grade and 26 high grade tumors) have been analyzed. Restriction fragment length polymorphism analysis directed at 5 suspected or established tumor suppressor gene regions (3p21-25, 11p15, 13q14, 17p11-13, and 18q21) was combined with immunohistochemical using Rb-PMG3-245 monoclonal antibody directed at the retinoblastoma (Rb) gene product. Tumor grade correlated with deletions of 3p (P = 0.004) and 17p (P = 0.063). Tumor stage correlated with deletions of 3p (P = 0.010), 17p (P = 0.015) and altered Rb expression (P = 0.054). Vascular invasion correlated only with deletions of 17p (P = 0.038). No marker correlated with positive lymph nodes. Our results suggest that altered Rb expression occurs in all grades and stages of bladder cancer but is more commonly associated with invasive tumors. Genetic alterations of 3p, 11p, 17p, and 18q are rare events in low grade, superficial tumors, whereas they are more common in high grade and invasive bladder cancer. The role of these genetic alterations in the prognosis of bladder cancer will require additional follow-up and further studies.