A b s t r a c t s 1 4 1

PATHOGENESIS OF RENAL CELL TUMORS: A (CYTO)-GENETIC MODEL

E. van den Bera ~, S. St0rkeP, T. DijkhuizeW, B. de Jong ~

Dept. of Medical Genetics ~, Gioningen, The Netherlands Dept. of PathologyL MOnster, Germany.

Renal cell cancers constitute a group of tumors that is highly heteroge- neous with respect to morphology and clinical behaviour. Based on macroscopic, histological and ultra.structural features, a detailed subtyping of renal cell tumors was proposed by St6rkeltL2L This classification of renal cell adenomas (RCA) and carcinomas (RCC) is based on eight basic cell and tumor types (entities) with charac~Leristic morphologic features: (I) RCCs of clear cell type, (2) RCAs/RCCs of chromophilic cell type, (3) RCAs/RCCs of chromophobic cell type, (4) RCCs of ductus Bellini cell type, (5) RCCs of transitional cell type, (6) RCCs o1" neuroendocrine type, (7) RCAs of onco- cytic type and (8) RCAs of metartephroid type. Cytogenetic and molecular genetic studies confirm the proposed eight morphological subtypes (~.3). Moreover, these studies may provide a clue for understanding the type spec- ific oncogenesis and progression.

Tumors with a proposed histogenesis from the proximal part of the nephr- on (clear cell and chromophilic typ e) amount to 85% of renal cancers, whereas tumors with a proposed histogenesis form the connecting tubule/collecting duct (chromophobic-, oncocytic-, and duct Bellini type tumors) amount to only 11%. The remaining types represent rare entities.

RCAs occasionally show a malignant behavior. A reasonable explanation for this exceptional behavior is that RCAs probably represent the benign side of a spectrum of renal cell tumors, with RCCs at the other extreme. If this "spectrum" concept for RCAs and RCCs is correct, then it may be expec- ted that there also exists an overlap with respect to (cyto)genetic abnormalities.

Based on this morphological classification and the (cyto)genetic analysis of a large sample of renal cell tumors together with the accumulated data in the literature, we now present a model for the pathogenesis of renal cell tumors.

References (" Thoenes Wet al Pathol Res Pract 1986; 181:125-143. (2) St6rkel Se t al World J Urol 1995; 13: 153-158. ~3) Berg van den E Int J Cancer ;t 993; 55: 223-227.

TWO CASES OF RENAL CELL CARCINOMA, CLEAR CELL TYPE, REVEALING A t(6;I I)(p21 ;q13)

T. Diikhuizen', E. van den Berg', S. St0rkeP, A. Geurts van Kessel 2, B. Jonssen ~, B. do Jong'

Dopl. ot Medical Get,olios, Ul~lv. ot GronlrlgeW, Dept. of Human Genetics, Univ. Hospital Nijmegen 2, The Netherlands, and the inst. of Pathology, MOnster, Germany 3

Clear cell renal cell carcinomas (RCCs) and renal oncocytomas are histolo- gically and cytogenetically distinct entities. According to the classification of Thoenes and St6rkel[ l ], they are thought to derive from different parts of the nephron. The clear cell RCCs find their origin in the proximal part of the tubule, whereas the oncocytomas arise from the intercalated cells of the collecting tubule. Cytogenetic data show distinct chromosomal patterns for both subtypes. The clear cell RCCs predominantly show 3p losses. Renal oncocytomas are cytogenetically heterogeneous, but two subgroups seem to emerge. Part of the oncocytomas show loss of chromosomes I and Y in combination, whereas others are characterized by a t(5; 11 ) or t(9; l l ) all with breakpoints in 1 l ql 3. In addition clear cell RCCs and oncocytomas have a different biologic behavior. RCCs of the clear cell type are malignant, but oncocytomas are considered to be benign neoplasms.

We present the cytogenetic data of two cases of clear cell RCC with oncocy- tic areas, arising in relatively young (female) patients (17 and 42 years old). Interestingly neither of them showed loss of (part of) the short arm of chromosome 3, specific for the clear cell RCCs. Both neoplasms had a t(6; l 1 )([o21 ;q 13) as the sole cytogenetic abnormality. The breakpoint in 11 ql 3 appeared to be similar to the one found in the oncocytomas. Molecular analysis of the breakpoint in case one however, revealed that it was different from the I 1 q 13 breakpoint in the t(5; l l ) oncocytomas published earlier [2]. The second case is currently being analysed.

In conclusion: Since the cytogenetic abnormalities of the present clear cell RCCs arc different from what one would expect in these tumors, there might be a relation between the chromosomal pattern and the distinct differentiati- on of these neoplasms. This might also be of importance for the prognosis of the patient. The first patient is alive and well after seven years of follow-up. Monitoring of the second patient should learn wheather these tumors tend to behave in a more benign fashion than clear cell RCCs usually do.

References 1 Thoenes et al Path Res Pract 86 181:125-143 2 Van den Berg et al Cancer Genet Cytogenet 79:164-168