A. Dam

Cytogenetics of 12 cases of renal adenocarcinoma.

The cytogenetics of 12 cases of renal adenocarcinoma are presented. Clonal abnormalities were found in nine patients. Worth mentioning are abnormalities of the X chromosome (1 X) and the chromosomes #1(3 X), #3(3 X), #7(4 X), #8(4 X), and #14(2 X). From our data and data from the literature it appeared that the chromosomal regions 3p11-p21, 1q21, 14q22, and Xp11 are important for the oncogenesis of renal cell carcinoma as well as increased dosage of chromosome #7 and loss or abnormalities of chromosomes #8 and #14.

Chromosomal changes in renal oncocytomas Evidence that t(5;11)(q35;q13) may characterize a second subgroup of oncocytomas

Many of the reported oncocytomas have different chromosome abnormalities, indicating that they comprise a cytogenetically heterogenous group of tumors consisting of potentially cytogenetic subgroups. We have performed cytogenetic studies on nine renal oncocytomas. Clonal abnormalities were present in eight tumors. The findings most observed were the loss of the Y chromosome, and abnormalities of chromosomes 1 and 22. We also observed telomeric associations (tas) in two tumors and structural aberrations of chromosomes 9p and 19q, as well as monosomy 10. In two cases we found a similar reciprocal t(5;11)(q35;q13) in two cases. Review of the literature disclosed one other oncocytoma with a t(5;11) (q35;q13). This suggests that t(5;11)(q35;q13) defines a (second) subset of oncocytomas apart from the subgroup specifically associated with the loss of chromosomes 1 and Y.

A MALIGNANT MIXED GONADAL STROMAL TUMOR OF THE TESTIS WITH HETEROLOGOUS COMPONENTS AND I(12P) IN ONE OF ITS METASTASES

A malignant mixed gonadal stromal tumor with mesenchymal heterologous elements of the testis is presented. This entity has been described in the ovary, but not hitherto in the testis. Karyotyping and ploidy measurement was done of the primary tumor and of an inguinal and lung metastases. The DNA ploidy and modal chromosome numbers were in agreement with each other in all samples. The most significant cytogenetic finding was the presence of the metacentric germ cell tumor marker i(12p) in an inguinal metastasis. This marker has been demonstrated in testicular and ovarian germ cell tumors and in a mixed Müllerian tumor, which raises the question of a possible relationship between the pluripotency of these tumors and the presence of i(12p).

A RESIDUAL MATURE TERATOMA WITH A MORE BALANCED KARYOTYPE THAN THE PRIMARY TESTICULAR NONSEMINOMA

We have been able to study the karyotypes and measure the DNA content in both the primary nonseminomatous germ cell tumor of the testes and the residual mature teratoma after chemotherapy of the same patient. Based on these and other studies, the mechanism of therapy-related differentiation in germ cell tumors of the testes is discussed.

Retinoic acid and cisdiaminodichloroplatinum in the treatment of murine teratocarcinomas in vivo in a nullipotent model

Induction of differentiation as a treatment modality for nonseminomatous germ cell tumors (NSGCTs) may promote the development of residual mature teratoma (RMT), which is usually associated with primary tumors that are capable of spontaneous somatic differentiation. Therefore, we studied the combination of a cytotoxic drug and a differentiation-inducing agent in vivo in three murine teratocarcinoma models with different levels of spontaneous somatic differentiation: E86-379 (moderate differentiation); NF-1 (poor differentiation); and MH-15 (no differentiation). We used retinoic acid (RA) as differentiation-inducing agent and cisdiaminodichloroplatinum (CDDP) as cytotoxic drug, plus a combination of both. In four separate experiments, the combination of RA and CDDP gave a significant further reduction of tumor size as compared with treatment with either RA or CDDP alone. Morphologically intact tumor after treatment with combined RA-CDDP contained a smaller proportion of undifferentiated tissue (embryonal carcinoma) than after CDDP alone. However, somatic differentiation was not induced in the tumor model lacking spontaneous somatic differentiation. Toxicity was reflected in loss of body weight and death of some animals and closely paralleled the degree of tumor reduction in all experiments.