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Malignant behaviour of incidentally found small renal cell carcinomas in renal graft donors and recipients
Malignant Behaviour of Incidentally Found Small Renal Cell Carcinomas in Renal Graft Donors and Recipients H. Wunderlich, K. Junker, H. Kosmehl, S. Wilhelm, O. Reichelt, and J. Schubert
A
LTHOUGH numerous studies have reported an increasing prevalence of small renal cell carcinomas (RCC),1,2 it remains uncertain whether this increased incidence is real. With the recent development and widespread use of imaging techniques, such as ultrasonography and computerized tomography, the frequency of incidental diagnosis of asymptomatic RCC has increased. The annual rate of incidentally found carcinomas has increased from 20% to 70%.3–5 The objective of this study was to evaluate the malignant behaviour of incidentally found small renal cell tumors in kidney graft donors and recipients and to determine the appropriate procedure for cases in which small renal tumors are newly detected at the time of preparation for transplantation. MATERIALS AND METHODS To elucidate the relationship between oncofetal fibronectin and the behaviour of small renal tumors, we examined the expression of all fibronectin isoforms and ED-B-Fn in 23 renal tumors each of up to 10 mm in size. Using shock frozen tissue, the distribution of the fibronectin isoforms was visualized immunhistochemically, using the monoclonal antibodies IST4 for all fibronectin isoforms and BC1 for ED-B-Fn (APAAP technique). The results were correlated to proliferative activity (Ki-67 index) and chromosomal aberrations (comparative genomic hybridization, CGH). The EDB-Fn synthesis was also investigated by RNA-RNA in situ hybridization.
RESULTS
Eight clear cell carcinomas, 1 metanephrogenic adenoma, 1 inflammatory pseudotumor, and 13 chromophilic adenomas were found on exploration. ED-B-Fn was visualized in all renal cell carcinomas, but not in renal adenomas. In RCC the source of the ED-B-Fn was the tumor as well as the stromal tissue. There was a positive correlation between the amount of oncofetal fibronectin deposition (ED-B-Fn) and the proliferative activity. Using CGH we found genetic aberrations of both adenomas and carcinomas. The results showed that the features of adenomas were gains of chro-
0041-1345/02/$–see front matter PII S0041-1345(02)03212-8 2224
mosome 7 and 17 and loss of the Y-chromosome. In small clear cell tumors loss of chromosomes 9 and 14 represented the genetic alterations that characterized progression. DISCUSSION
With regard to the cytogenetic characteristics of renal cell carcinomas and adenomas, the restricted expression of oncofetal fibronectins may gain diagnostic importance. The higher amount of ED-B-Fn appears to be a marker of active stromal recruitment and could serve to distinguish mutated cell complexes that are resting versus displaying active stroma interactions. Because donor candidates display a renal tumor incidence of about 1%, we recommend careful ultrasound screening of the native kidneys before renal explantation and immediate preparation of the kidney surface for macroscopic lesions, especially in donors older than 45 years. In cases of small renal lesions, we recommend immediate section for microscopic examination before transplantation to prevent implantation of organs from donors with malignant tumors into otherwise healthy patients. Additionally, we recommend paraffin-embedding of the tumor-tissue for a correct histologic examination. By extending cold ischemia time by about 3 to 6 hours, we receive important information about tumor characteristics, thereby avoiding neoplastic cell seeding. REFERENCES 1. Ho ¨lzel D, Altwein JE: Urologe [A] 130:134, 1991 2. Wunderlich H, Wilhelm St, Reichelt O, et al: Urol Int 67:24, 2001 3. Bretheau D, Lechevallier E, Eghazarian C, et al: Eur Urol 27:319, 1995 4. Gross AJ, Dieckmann KP, Bu ¨ttner P, et al: Urologe [A] 31:306, 1992 5. Nakano E, Iwasaki A, Seguchi T, et al: Eur Urol 21:294, 1992 From the Department of Urology, Friedrich-Schiller University, Jena, Germany. Address reprint requests to Dr Heiko Wunderlich, MD, Dept. of Urology, Friedrich-Schiller-University, 07740 Jena, Germany. E-mail: [email protected]
© 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2224 (2002)
A
LTHOUGH numerous studies have reported an increasing prevalence of small renal cell carcinomas (RCC),1,2 it remains uncertain whether this increased incidence is real. With the recent development and widespread use of imaging techniques, such as ultrasonography and computerized tomography, the frequency of incidental diagnosis of asymptomatic RCC has increased. The annual rate of incidentally found carcinomas has increased from 20% to 70%.3–5 The objective of this study was to evaluate the malignant behaviour of incidentally found small renal cell tumors in kidney graft donors and recipients and to determine the appropriate procedure for cases in which small renal tumors are newly detected at the time of preparation for transplantation. MATERIALS AND METHODS To elucidate the relationship between oncofetal fibronectin and the behaviour of small renal tumors, we examined the expression of all fibronectin isoforms and ED-B-Fn in 23 renal tumors each of up to 10 mm in size. Using shock frozen tissue, the distribution of the fibronectin isoforms was visualized immunhistochemically, using the monoclonal antibodies IST4 for all fibronectin isoforms and BC1 for ED-B-Fn (APAAP technique). The results were correlated to proliferative activity (Ki-67 index) and chromosomal aberrations (comparative genomic hybridization, CGH). The EDB-Fn synthesis was also investigated by RNA-RNA in situ hybridization.
RESULTS
Eight clear cell carcinomas, 1 metanephrogenic adenoma, 1 inflammatory pseudotumor, and 13 chromophilic adenomas were found on exploration. ED-B-Fn was visualized in all renal cell carcinomas, but not in renal adenomas. In RCC the source of the ED-B-Fn was the tumor as well as the stromal tissue. There was a positive correlation between the amount of oncofetal fibronectin deposition (ED-B-Fn) and the proliferative activity. Using CGH we found genetic aberrations of both adenomas and carcinomas. The results showed that the features of adenomas were gains of chro-
0041-1345/02/$–see front matter PII S0041-1345(02)03212-8 2224
mosome 7 and 17 and loss of the Y-chromosome. In small clear cell tumors loss of chromosomes 9 and 14 represented the genetic alterations that characterized progression. DISCUSSION
With regard to the cytogenetic characteristics of renal cell carcinomas and adenomas, the restricted expression of oncofetal fibronectins may gain diagnostic importance. The higher amount of ED-B-Fn appears to be a marker of active stromal recruitment and could serve to distinguish mutated cell complexes that are resting versus displaying active stroma interactions. Because donor candidates display a renal tumor incidence of about 1%, we recommend careful ultrasound screening of the native kidneys before renal explantation and immediate preparation of the kidney surface for macroscopic lesions, especially in donors older than 45 years. In cases of small renal lesions, we recommend immediate section for microscopic examination before transplantation to prevent implantation of organs from donors with malignant tumors into otherwise healthy patients. Additionally, we recommend paraffin-embedding of the tumor-tissue for a correct histologic examination. By extending cold ischemia time by about 3 to 6 hours, we receive important information about tumor characteristics, thereby avoiding neoplastic cell seeding. REFERENCES 1. Ho ¨lzel D, Altwein JE: Urologe [A] 130:134, 1991 2. Wunderlich H, Wilhelm St, Reichelt O, et al: Urol Int 67:24, 2001 3. Bretheau D, Lechevallier E, Eghazarian C, et al: Eur Urol 27:319, 1995 4. Gross AJ, Dieckmann KP, Bu ¨ttner P, et al: Urologe [A] 31:306, 1992 5. Nakano E, Iwasaki A, Seguchi T, et al: Eur Urol 21:294, 1992 From the Department of Urology, Friedrich-Schiller University, Jena, Germany. Address reprint requests to Dr Heiko Wunderlich, MD, Dept. of Urology, Friedrich-Schiller-University, 07740 Jena, Germany. E-mail: [email protected]
© 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2224 (2002)