Cytogenetic Profile Predicts Prognosis of Patients With Clear Cell Renal Cell Carcinoma

• Published in: Journal of clinical oncology Vol. 27; no. 5; pp. 746 - 753
• Main Authors: KLATTE, Tobias, NAGESH RAO, P, DE MARTINO, Michela, LAROCHELLE, Jeffrey, SHUCH, Brian, ZOMORODIAN, Nazy, SAID, Jonathan, KABBINAVAR, Fairooz F, BELLDEGRUN, Arie S, PANTUCK, Allan J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.02.2009
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Chromosome Deletion; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 4; Chromosomes, Human, Pair 5; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 7; Chromosomes, Human, Pair 8; Chromosomes, Human, Pair 9; Female; Humans; Karyotyping; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Kidneys; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Prognosis; Prospective Studies; Sex Chromosome Aberrations; Trisomy; Tumors; Tumors of the urinary system; Kidney disease; Human; Clear cell carcinoma; Urinary system disease; Cancerology; Prognosis; Kidney cancer; Cytogenetics; Grawitz tumor; Malignant tumor; Predictive factor; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2007.15.8345

The majority of cytogenetic studies in renal cell carcinoma (RCC) have been impaired by small sample size, retrospective character, and lack of a survival end point. We prospectively studied the prognostic impact of cytogenetic abnormalities on a larger cohort of patients having up to 108 months of follow-up. Tumors of 282 patients who underwent nephrectomy for clear cell RCC were cytogenetically analyzed. Results were correlated with pathological factors and disease-specific survival. The most frequently observed cytogenetic abnormalities were loss of 3p (60%), gain of 5q (33%), loss of 14q (28%), trisomy 7 (26%), loss of 8p (20%), loss of 6q (17%), loss of 9p (16%), loss of 4p (13%), and loss of chromosome Y in men (55%). Tumors with loss of 3p presented at lower TNM stages. Loss of 4p, 9p, and 14q were all associated with higher TNM stages, higher grade, and greater tumor size. A deletion of 3p was associated with better prognosis (P = .03), while loss of 4p (P < .001), loss of 9p (P < .01), and loss of 14q (P < .01) were each associated with worse prognosis. Loss of the Y chromosome led to improved progression-free survival in metastatic patients (P = .02). In multivariate analysis, loss of 9p was retained as an independent prognostic factor. This cytogenetic study serves as a proof of principal that genetic information, such as loss of chromosome 9, can be obtained from widely available technology, and can provide additional prognostic information to standard clinicopathologic variables.