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We report a new case of renal cell carcinoma with the translocation (X;1)(p11;q21) and complex structural rearrangements in a female patient of 64 years of age. We analyzed abnormalities using FISH to identify chromosomal rearrangements, and wonder whether the translocation (X;1) could represent a particular subentity in renal cell carcinoma with distinct histologic features.

The sole cytogenetic abnormalities encountered in two childhood anaplastic intracerebral ependymomas were an isodicentric chromosome 22 in one case and an unbalanced chromosome 22 translocation associated with a partial deletion in the other. Fluorescence in situ hybridization analysis showed that the common 22q arm loss did not involve the rhabdoid region but included the EWS and NF2 loci. These results, in conjunction with data in the literature, suggest that the most frequently recurrent genomic loss in ependymomas does not involve the proximal 22q11.2 chromosome region but is localized distally to the hSNF5/INI1 locus. A tumor-suppressor gene, independent of the NF2 gene, which seems to be exclusively involved in intramedullary spinal cord ependymomas, might be implicated in the genesis of these intracranial tumors.

The implication of environmental carcinogens in childhood cancer is still unknown. To assess a possible link between DNA damage and alterations of the tumor suppressor gene p53, blood samples of 21 children with malignancies were examined for the presence of micronuclei in lymphocytes using the cytokinesis blocked micronucleus assay (CBMA). The constitutional karyotypes were analyzed for chromosome abnormalities and the presence of anti-p53 antibodies in blood sera was evaluated by an enzyme-linked immuno sorbent assay (ELISA). A control group of 20 children was also included. The rates of micronucleated cells were 5.1 per thousand+/-3.9 and 2.4 per thousand+/-2.3 for the cancer and control groups, respectively. The difference between the groups were statistically significant (P0.05 by the Mann-Withney rank sum test). Two children in the cancer group showed extensive chromosome breakage in lymphocytes. The sera of two other children from the cancer group and of one child from the control group contained anti-p53 antibodies. Chromosome breakage and anti-p53 antibodies from the five children were associated with increased micronucleated cell rates. The results of the present study suggest that genotoxic events can occur in the lymphocytes of children with a cancerous state.

Ependymomas are glial tumors. They constitute approximately 5-10% of intracranial tumors. Ependymomas are tumors which can recur. Predictive factors of outcome in ependymomas are not well-established. Karyotypic studies on ependymomas are relatively scarce, and no specific chromosomal change has been described in these neoplasms. We performed a cytogenetic study of 33 ependymomas, of which eight were recurrent tumors, to determine the type and incidence of cytogenetic changes.

We performed a cytogenetic study on 24 pilocytic astrocytomas: 23 in children and 1 in a young adult. We observed 12 normal karyotypes. In 12 karyotypes with structural and/or numerical abnormalities, chromosomes 7, 8, and 11 were most frequently involved. One case recurred and presented chromosomal abnormalities (hyperdiploidy) in the first tumor and additional structural abnormalities in the second tumor. We believe that chromosomal abnormalities in pilocytic astrocytomas are frequent and indicate tumoral progression.

Medulloblastomas are the most frequent primitive neurectodermal tumors in children. An isochromosome for the long arm of 17, i(17q), is found in 30% of medulloblastomas. For some authors, this abnormality is observed in cases with a shorter survival time. In our cytogenetic studies of 30 medulloblastomas, we observed i(17q) in only three cases, a monosomy 17 in two cases, a monosomy 22 in four cases, nonspecific numerical or structural abnormalities in five cases, and normal karyotypes in 12 cases. We compared the results of karyotypic analysis after culture and FISH with a chromosome 17 alpha satellite DNA probe on interphase nuclei in five cases of medulloblastoma. In one case, i(17q) was only observed in four cells in karyotypic analysis, in three cases a normal karyotype was found, and in one case karyotypic analysis was impossible. In all of these cases, i(17q) was observed in a great number of nuclei by FISH on interphase nuclei. Our study shows that the FISH on interphase nuclei permitted us to observe i(17q) in the cases where it was not or could not be completely detected by karyotypic analysis. The association of these two techniques is required to detect i(17q), an abnormality whose prognosis value in medulloblastomas is now recognized.

PDGFs and their receptors expression were examined in a series of 46 meningiomas by using specific monoclonal antibodies. The immunostaining was quantified by an image analyser and the results correlated with clinical and morphological data (histological type and grade). In addition, since the PDGFB chain is encoded by the c-sis proto-oncogene localized on chromosome 22 and because monosomy 22 has been frequently reported in meningiomas, PDGFs and PDGFRs expression have been correlated with cytogenetic analysis performed in 29 cases. The results demonstrate PDGF A and PDGF B expression in most meningioma specimens and co-expression of these growth factors in numerous cells. PDGF A and B immunoreactivity was related to histological grade. PDGFR beta expression was strong in almost all meningiomas whereas PDGFR alpha was low. PDGFR alpha expression was related to tumour location and grade and PDGFR beta to histological subtype only. The cytogenetic analysis was not related to PDGFB chain expression. Taken together these data further confirm PDGF and PDGFR expression in human meningioma; PDGF may exist as an heterodimer (AB) as well as its receptor. The lack of correlation between cytogenetic analysis and PDGF values, the low level of PDGFB in recurrent meningiomas suggests that it is unlikely that the c-sis proto-oncogene plays an important role in the genesis of meningiomas.

This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 and 45, XY, -8, add(12)(q–ter) for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished. Key Words: renal cell carcinoma • low grade tumour of the collecting ducts

Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children. As prognostic factors for this disease are not well-established, it seemed important to identify genetic features in these tumors. We present data provided by recent studies on conventional cytogenetic, molecular cytogenetic and molecular genetic in correlation with prognosis in these tumors.

Lipoblastoma is an uncommon benign soft tissue tumor arising from embryonal mesenchymal cells. It occurs mostly during early childhood with a predilection for the extremities, trunk, head and neck. This tumor tends to spread locally and no metastatic potential has been reported. Complete surgical resection is mandatory to prevent local recurrence. MRI provides excellent presurgical delineation of the tumor and confirms its fatty nature. Histology demonstrates the presence of lipoblasts in different stages of maturation; cytogenetic evaluation often discloses chromosomal anomalies of tumoral cells. A case of lipoblastoma of the buttock in a 10 month infant associated with anomalies of chromosome 8 is reported.

Fluorescence in situ hybridization (FISH) analysis in a case of infant acute monocytic leukemia M5 revealed a complex rearrangement between chromosomes 10 and 11, leading to the disruption of the MLL gene. Using two painting probes for chromosomes 10 and 11 and a specific probe for the MLL gene localized on 11q23, we observed a paracentric inversion of the 11q13-q23 fragment translocated to 10p12. Molecular analysis showed that AF10 localized on 10p12 was the fusion partner gene of MLL in this rearrangement (10;11). This report underlined the usefulness of FISH and molecular techniques in identifying complex rearrangements.

It is known that, following radiotherapy, secondary cancer may occur after a long latent period. Few cytogenetic studies have been reported on tumors of the central nervous system occurring after radiotherapy. We report the cytogenetic study of six cases of radiation-induced meningiomas. In all cases, we observed the same chromosome abnormality, der(1)(1qter--1p11::22q12--22pter). SKY and CGH techniques allowed us to identify the chromosomal abnormalities. We suggest that a gene localized on 1p13 is involved in radiation-induced meningiomas.

Cytogenetic analysis provides important information for diagnosis and prognosis in some tumors. But karyotype analysis can be difficult in some cases, because metaphase chromosomes are contracted. New techniques, such as fluorescence in situ hybridization and, more recently, spectral karyotyping, or SKY, based on the hybridization of 24 fluorescently labeled chromosome painting probes, allow the detection and identification of complex chromosomal rearrangements. We report here a case of primary central nervous system lymphoma in which chromosomal rearrangements and marker chromosomes not identified by a routine cytogenetic technique were clarified by SKY. This shows the value of the SKY technique in the cytogenetic diagnosis of tumors.

The correlation between cytogenetic and histopathological findings were analysed in 189 meningiomas. The tumors were classified according to increasing degrees of anaplasia. We observed normal karyotype or only monosomy 22 in grade 1 (benign) tumors, while in grade 3 (anaplastic) only 1.5% of karyotypes were normal. Grade 2 (atypical) and 3 (anaplastic) tumors showed complex structural abnormalities. Loss of chromosome 14 were only found in grade 3. In cases with complex structural rearrangements, fluorescence in situ hybridization technique (FISH) has been realized and permitted a best identification of abnormalities. In our series, five patients recurred. They presented chromosomal abnormalities. These complex karyotypes in recurrent meningiomas might indicate aggressive tumor characteristics. Our results indicate histolopathological and cytogenetics correlations might represent a prognostic factor in meningiomas.

We report two cases of brain tumors, one childhood medulloblastoma and one adult glioblastoma with an unusual chromosomal abnormality: a t(1;19)(q23;q13). We analyzed these karyotypes using fluorescence in situ hybridization (FISH) and wonder if this chromosomal aberration could represent a particular entity in these brain tumors like t(1;19) in ALL.

Some controversy has existed regarding the nosology of meningeal hemangiopericytoma. In the WHO's classification of 1979 these tumours were included as a subgroup of meningiomas, but for some authors, they should not be classified as meningiomas. Cytogenetic studies on meningioma demonstrate monosomy or partial deletion of chromosome 22 in 60% of these tumors. There have been few cytogenetic studies about meningeal hemangiopericytoma. We present here the results of cytogenetic studies and fluorescence in situ hybridization in six cases of meningeal hemangiopericytoma. In these tumours we have never found monosomy 22, but all six cases were hyperdiploid. These cytogenetic data might provide additional evidence to differenciate the meningeal hemangiopericytoma from the meningioma.

Primary central nervous system (PCNS) lymphoma is a relatively rare disease. The Epstein-Barr virus (EBV) has often been implicated in the development of lymphomas. Few cytogenetic. studies on PCNS lymphomas have been reported. We describe here an unusual case of PCNS B cell lymphoma, centroblastic polymorphic type without coexistent immune deficiency. The cytogenetic study showed unusual abnormalities: t(l;9) (q25;p21); del (6) (q14 q25), trisomy 12 and in addition one clone with trisomy 7 and loss of chromosome X. We did not observe any chromosome 14 abnormality, which is more commonly reported in PCNS lymphomas.

To assess the expression of the homeogene Pax-2 in adult renal cell carcinomas, we did a retrospective immunohistochemical analysis of 56 frozen tumor samples representing all major histologic subtypes of renal tumors. There were 33 conventional renal cell carcinomas (58.9%), 12 papillary renal cell carcinomas (21.4%), 4 chromophobe cell renal carcinomas, 4 urothelial cell renal carcinomas, and 3 oncocytomas. Forty-five tumors (62.5%) were localized, and 21 tumors had extrarenal involvement. Eight patients (14%) had metastatic disease at the end of the follow-up. We searched for relationships between Pax-2 expression and nuclear grading, TNM staging, Ki-67 proliferation index, expression of transforming growth factor-beta1 (TGF-beta 1), an in vitro down-regulator of Pax-2 expression, and finally cytogenetic abnormalities. All histologic subtypes expressed Pax-2 protein, except urothelial renal carcinomas. The highest expression was in papillary renal cell carcinomas. In this subtype, all tumors and 83.3% +/- 12.3% of tumor cells were immunoreactive for Pax-2. All but 2 conventional renal cell carcinomas expressed Pax-2, but with 26.3% +/- 29.6% of immunoreactive cells (P.001). Pax-2 expression was not correlated with nuclear grading (P =.6), tumor size (P =.3), and TGF-beta 1 expression (P =.1). Nevertheless, Pax-2 expression correlated with the Ki-67 proliferation index only for the conventional histologic subtype (P =.03). In this histologic subtype, Pax-2 expression was higher in patients with metastatic disease than in those without (P =.02). Pax-2 expression was not associated with specific cytogenetic abnormalities like trisomy 7 (P =.1), 3p deletion (P =.5), and hyperdiploidy (P =.2). TGF-beta 1 expression, positive in 33 tumors (59%), was not correlated with either Pax-2 expression (P =.1) or current prognostic factors such as nuclear grading (P =.2). Interestingly, we also observed an expression of TGF-beta RI and TGF-beta RII in the tumors with high nuclear grading (P =.005). We conclude that Pax-2 protein is expressed in all major histologic subtypes of renal cell carcinomas. The pattern of expression differs between these subtypes. Pax-2 expression in conventional renal cell carcinomas is correlated with the proliferation index and is significantly higher in patients with metastatic disease. HUM PATHOL 32:282-287.