194 Abstracts

CYTOGENETIC AND IMMUNOHISTOCHEMICAL CHARACTERIZATION OF

A PRIMARY CELL CULTURE (KUMI) OBTAINED FROM AN UROTHELIAL

CARCINOMA OF THE URETER.

P. Grammatico (1),K. Steindl (1),C. Mordenti (1),M.

Governatori (2),C. Di Rosa (i) and G. Del Porto (1).

(I) Cattedra di Genetica Medica Universit~ "La Sapienza"

c/o Osp. L. Spallanzani,Via Portuense 292 00149 ROMA,ITALY

(2) Divisions Urologica Malpighi, Osp. S. Camillo, ROMA

Italy.

The aut/ors report cytogenetic and immunohistochemical

results obtained from the analysis of a primary cell

culture of an urothelial cell carcinoma of the ureter

(KUMI). The patient was histologically classified as

stage pT2NMo and grade G2 and he undergo a peridical

follow-up. Cytogenetic analysis evidentiated as the sole

chromosomal aberration a trisomy of the chromosome 20.

mmunohistochemical study was performed using different

antibodies in order to obtain a better characterization

of this cell culture. The autors consider the significance

of the chromosomal marker and the immunohistochemical

results regarding the etiology, the pathogenesis and the

prognosis in this tumor.

CYTOGENETIC ANALYSIS OF PROSTATE ADENOCARCINOMAS BY INTERPHASE DNA IN SITU HYBRIDIZATION. J.C. Alers, P.J. Krijtenburg, F.T. Bosman, Th. H. van der Kwast and H. van Dekken, Dept. of Pathology, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR ROTTERDAM, The Netherlands.

The amount of cytogenetic information on prostate cancer is relatively sparse. In prostatic adenocarcinomas, a consistent primary cytogenetic change has yet to be identified. Cytogenetic studies of prostate cancer by karyotyping of metaphase spreads are hampered by the preferential growth of normal (diploid} cells and by the low mitotic index of the cancer cells. Therefore, we have applied non-isotopic in situ hybridization (ISH) with a set of (peri)centromeric chromosome specific DNA probes to routinely processed tissue sections, thus allowing both cytogenetic and hietologic analysis. Twenty-five 25 primary prostate adenocarcinomaa from radical prostatectomies were taken to I) search for the presence of numerical chromosomal aberrations and II) to correlate karyotypic abnormalities with morphological and prognostic characteristics. Our results show numerical aberrations (+1, +7, -10, -15, -Y) of at least one chromosome in about 50% of the patients. Loss of the Y chromosome was the most common finding. Genetic heterogeneity in prostate cancer was demonstrated by the focal appearance of the chromosomal aberrations. Loss of chromosome i0 and gain of chromosome 7 seemed to be associated with more advanced prostate cancers. Currently, we are investigating the occurrence of chromosomal abnormalities in pairs of primary prostatic adenocarcinomas and hematogenic metastases. Also preliminary results of the latter study will be shown at the meeting.

PkOSTATIC INTRAEPITHELIAL NEOPLASIA (PIN) INVASIVE CARCINOMA OF THE PROSTATE: THE SAME GENETICAL ENTITY ? S.Sz~cs* and H.Zitzelsberger#, Institut f~r Pathologie der Technischen Universit~t MHnchen* and GSF Institut fHr Strahlenbiologie, Neuherberg, FRG

Premalignant lesions are described in a number of organs, such as uterine cervix, urothelium, respiratory epithelium and the gastrointestinal tract. PIN fulfills the majority of the requirements for a premalignant lesion of the prostate. A strong assotiation of high grade PIN with invasive carcinoma has been recognized. Radical therapy, however, is indicated only when invasive tumor can be clearly demonstrated. Several studies have been carried out to elucidate the patho

biology of the invasive carcinoma including genetic studies, but nothing is known about the genetic of the PIN cells. Do have the carcinoma cells different chromosomal alterations from the cells in PIN ? Now, employing fluorescence in situ hybridization (FISH) a

comparison of cells in PIN and invasive carcinoma for certain chromosomes can be performed. To find out which chromosomes are preferentially involved, primary cultures from invasive cancer were established and subsequently analyzed by conventional cytogenetic methods. Trisomy 7 become apparent as the most frequent numerical

aberration. Therefore we used for hybridization a chromosome 7 specific DNA-probe in paraffin embedded tissue sections for invasive carcinoma, for PIN and for nontumorous tissue. 16 cases with both, invasive tumor and PIN have been evaluated. Scoring 200 hybridized cells of relevant areas in each case revealed abnormalities exclusively in invasive tumor and/or PIN areals in 11 cases. 6 cases showed trisomy 7, 5 exhibited polyploid cells in both, tumor and PIN areals.(Confirmed by double hybridization for chromosome 7, plus 8 or 12). We found the same distribution of aberrations of chromosome 7 in both, invasive carcinoma and PIN. Our finding suggest, that PINs are characterized by the same

numerical cytogentic marker like carcinoma cells.

CYTOGENETIC EVIDENCE THAT CARCINOMA IN SITU IS THE PRECURSOR LESION FOR INVASIVE TESTICULAR GERM CELL TUMORS Jannie van Echten, Marian Stoepker, Beike Leegte, Leendert Looijenga, Bauke de Jong and J Wolter Oosterhuis, Dept. of Medical Genetics, University of Groningen, Ant. Deusinglaan 4, 9713 AW Groningen, and Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Carcinogenesis of testicular germ cell tumors (TGCTs) probably starts during intrauterine life. Based on immunohistochemical and ultrastructural studies carcinoma in situ (CIS), derived from premalignant gonocytes is supposed to be the precursor for adult TGCTs except spermatocytic seminoma. Cytogenetic investigation of CIS may support this vision and is important to understand the progression of CIS to invasive tumor and may shed light on the pathogenesis of TGCTs. A cytogenetic study of two cases of CIS and their adjacent invasive tumors (respectively nonseminomatous germ cell tumor (NSGCT) and seminoma) revealed similarities between the different lesions in the same patient. The first case showed an identical number of copies of the chromosomes X, i, 2, 3, 4, 7, 8, 12, 14, 15, 16, 17, 19, 21, and 22 and i(12p). In the second case an i(15q) was found as the sole common structural abnormality. These results present for the first time cytogenetic evidence that CIS is the precursor lesion for invasive NSGCTs and seminoma.