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Biomedical subjects

F Mertens

Publications and source records attributed to F Mertens.

At least 127 records · Page 7Linked to original sources
PubMed1996

Correlation between karyotypic pattern and clincopathologic features in 125 breast cancer cases.

A correlation analysis was performed on 125 cytogenetically characterized breast cancer cases to assess the relationship between the tumor karyotype and clinicopathologic features. The carcinomas of young women had a higher modal chromosome number than those of older women. The number of chromosomal aberrations and modal chromosome number were also found to correlate with the histologic type, grade and mitotic activity of the tumor. Whereas all lobular carcinomas were karyotypically normal or near-diploid, more than 3 aberrations and sometimes near-triploid or near-tetraploid karyotypes were common findings in ductal carcinomas, especially in grade-III tumors and in tumors showing high mitotic activity in vivo. Karyotypes with cytogenetically unregulated clones and unbalanced structural chromosomal rearrangements were more frequent in infiltrating than in in situ carcinomas but, at least as far as the second of these 2 characteristics is concerned, especially in infiltrating carcinomas that also had an in situ component. The presence of cytogenetic polyclonality correlated with tumor grade. Although recurrent chromosome aberrations were significantly more common in ductal than in lobular carcinomas, none of these breast cancer-associated anomalies seemed to be specific for any particular clinicopathologic parameter. The associations between modal chromosome number and mitotic activity and between cytogenetic polyclonality and tumor grade were found to be statistically significant in multivariate models. No correlations was seen between the karyotypic findings and tumor size or the presence of axillary-lymph-node metastases.

Adult↗
PubMed1996

Fusion of the EWS and CHOP genes in myxoid liposarcoma.

The translocation t(12;16)(q13;p11), which cytogenetically characterizes myxoid liposarcomas (MLS), results in a fusion of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a chimeric FUS/CHOP gene. We have identified two cases of MLS with translocations giving rise to recombination between 12q13 and 22q12. The result was a fusion of the N-terminal part of the EWS gene in 22q12, involved in a number of mesenchymal tumor types, with the CHOP gene and the creation of an EWS/CHOP chimeric gene. The presence of the EWS/CHOP chimeric gene in MLS shows that (i) the N-terminal part of FUS may be replaced by the N-terminal part of EWS in a CHOP fusion oncoprotein (ii) the two N-terminal parts, when fused to certain transcription factors, have a common or very similar oncogenic potential and (iii) the tumorigenic process in MLS and the morphogenetically distinctly different EWS-associated tumor types may be related.

Amino Acid Sequence↗
PubMed1996

Cytogenetic studies on fine-needle aspiration samples from osteosarcoma and Ewing's sarcoma.

The preoperative multidrug chemotherapy of osteosarcoma and Ewing's sarcoma patients requires a reliable diagnosis. There are several advantages with obtaining the diagnosis by fine-needle aspiration (FNA) and cytologic examination. Although cytologic criteria have been defined, adjunctive methods such as cytogenetic analysis are valuable to support the diagnosis. We have cytogenetically analyzed FNAs from 18 primary bone sarcomas (six osteosarcomas and 12 Ewing's sarcomas). Two of the osteosarcomas showed abnormal, complex karyotypes seen in most highly-malignant osteosarcomas. Seven Ewing's sarcoma aspirates displayed abnormal karyotypes; five of these had the characteristic 11;22 translocation, and in one of these cases molecular genetic analysis revealed the hybrid EWS/FLI1 transcript. Since only two of six osteosarcomas showed clonal changes, chromosomal analysis of FNAs from suspected osteosarcoma seems to be of limited value, but may in some cases support the diagnosis of high-grade malignancy. In Ewing's sarcomas, however, the finding of an 11;22 translocation was valuable and strongly supported the cytologic diagnosis. As shown in one case, the material obtained by FNA is sufficient for cytologic, cytogenetic, and molecular genetic analysis.

Adolescent↗
PubMed1996

Clonal chromosome abnormalities in two chemodectomas.

Short-term cultures from two histologically benign chemodectomas, one from the carotid body and one from the vagal nerve, were analyzed cytogenetically. The former had a small abnormal clone with the karyotype 46,XX,t(3;19)(q21;q13),t(12;15) (p13;q12-14), whereas the majority of the cells from the latter tumor displayed two related abnormal clones: 46,XY,i(I)(q10)/ 46,iderm,add(2)(q37). The findings add to the evidence that chemodectomas are heterogeneous neoplasms and suggest that the heterogeneity may possibly be associated with the site of origin.

Carotid Body Tumor↗
PubMed1996

Ring chromosomes in parosteal osteosarcoma contain sequences from 12q13-15: a combined cytogenetic and comparative genomic hybridization study.

Seven parosteal osteosarcoma (POS) samples, six of which were cytogenetically characterized, were studied by using comparative genomic hybridization (CGH). All samples showed DNA sequence copy number changes (mean, six aberrations/tumor; range, 1-13); gains were more frequent than losses. Gain of 12q13-15 sequences was found in every tumor and correlated with the presence of ring chromosomes. High-level amplification, which was detected in four tumors, was seen only in chromosome 12, with 12q13-14 as the minimal common region. By using chromosome painting, one of the rings of one case was shown to be composed entirely of chromosome 12 material. Together with previous data, our findings show that gain of 12q13-15 sequences is a characteristic feature of POS and that these sequences are contained within the ring chromosomes.

Adolescent↗
PubMed1996

Different cytogenetic patterns in skeletal breast cancer metastases.

Short-term cultures of breast cancer metastases to bone from two patients were analyzed cytogenetically. One metastasis had a complex hypotriploid karyotype with numerous marker chromosomes, whereas the other had simple karyotypic changes in three unrelated clones, 46,XX,t(4;11 )(p14;p 13)/45,XX,- 19/46,XX,del(3)(p 13p23), suggesting that the metastasis had originated from a simultaneous invasion of multiple cells from the primary tumor. The metastasis with complex chromosomal aberrations developed quickly as part of a clinically aggressive disease, whereas that with simple changes developed more than 20 years after the initial breast cancer diagnosis. Our findings therefore indicate that the tumor karyotype may play a role in determining the clinical course in patients with breast cancer.

Bone Neoplasms↗
PubMed1996

19p+ marker chromosome correlates with relapse in malignant fibrous histiocytoma.

In this study, we examined the relationship of 19p13 aberrations, usually leading to addition of unknown material (19p+), and ring chromosomes to clinical outcome in patients with malignant fibrous histiocytoma (MFH). Analysis of 69 MFHs revealed 19 tumors with 19p+ and 24 tumors with ring chromosomes. After a median follow-up period of 36 months, 24 patients developed metastases, and 27 patients developed local recurrences. Ten patients had both local recurrences and metastases. Local recurrence was more common in association with 19p+ than without. Metastasis was more common with 19p+ tumors in high-risk patients (tumor size > 5 cm and grade III-IV; n = 48) than those without 19p+. There was a trend suggesting fewer relapses after tumors with ring chromosomes. 19p+ may be an independent marker of unfavorable outcome in MFH.

Adult↗
PubMed1996

Primary vs. secondary neoplasia-associated chromosomal abnormalities--balanced rearrangements vs. genomic imbalances?

Two quite distinct neoplasia-associated karyotypic patterns are emerging. One is characterized by simple and disease-specific abnormalities, and the other is characterized by multiple and nonspecific aberrations. The former pattern is typical of most leukemias and lymphomas and of some mesenchymal tumors, but it is rare in epithelial neoplasms. The latter pattern is found in most epithelial tumor types, in several mesenchymal neoplasms, but in only a few hematologic malignancies. Primary chromosome aberrations, which are believed to be essential in establishing the neoplasm, and secondary changes, which are considered to be important in tumor progression, may be distinguished in the tumors characterized by simple and disease-specific abnormalities. Here, we propose that these aberrations are genetically and hence, most likely, functionally distinct. Primary abnormalities lead to specific gene rearrangements, whereas secondary chromosomal changes result in large-scale genomic imbalances. According to this hypothesis, there are no unbalanced primary aberrations, only secondary imbalances masquerading as primary. This proposition has a number of conceptual ramifications. First, the genetic mechanisms underlying tumor initiation and progression would seem to be totally different. Second, the elucidation of the molecular consequences of the secondary aberrations will be an arduous task, even if one were to adhere to the view that cytogenetically identified genomic imbalances may be reduced to simple gains or losses of single oncogenes or tumor suppressor genes. Third, the cytogenetic diagnosis of neoplasms will have to take into account that an unbalanced "primary" abnormality is secondary to a submicroscopic, truly primary change of major diagnostic and prognostic importance.

Chromosome Aberrations↗
PubMed1996

Chromosome aberrations in prophylactic mastectomies from women belonging to breast cancer families.

Short-term cultures of samples from eight prophylactic mastectomies from five unrelated women who were genetically predisposed to breast cancer were analyzed cytogenetically. Clonal chromosome abnormalities were detected in five breasts. Three samples from two women had aberrations involving the short arm of chromosome 3, with a breakpoint in 3p14 in common. Three samples from three women had rearrangements of 1q. Two of them, one of which also displayed a 3p14 rearrangement, shared a breakpoint in 1q41. Both 1q41 and, in particular, 3p14 have been reported to be rearranged frequently in malignant breast proliferations. Whether alterations of genes in these bands are essential in mammary tumorigenesis and, if so, whether they are equally important in sporadic and in hereditary cases remains to be explored.

Adult↗
PubMed1996

Genomic PCR detects tumor cells in peripheral blood from patients with myxoid liposarcoma.

Myxoid liposarcoma (MLS) is the most common subtype of liposarcoma. The cytogenetic hallmark of MLS is the pathognomonic t(12;16)(q13;p11), present in more than 85% of cases. The translocation leads to the fusion of the CHOP and FUS genes at 12q13 and 16p11, respectively, and the generation of a FUS/CHOP hybrid protein. The presence of a tumor-specific chimeric gene makes it possible to identify MLS cells by polymerase chain reaction (PCR). We have analyzed peripheral blood samples obtained during a 10-year period at diagnosis of primary and/or recurrent disease in 19 MLS patients with t(12;16) and in one MLS patient with t(12;22;20), resulting in the fusion of the CHOP and EWS genes. Nested PCR on genomic DNA from blood samples amplified FUS/CHOP hybrid fragments in three patients and EWS/CHOP in the patient with t(12;22;20). There was no obvious association between PCR findings and clinical outcome, but larger series are needed to draw any firm conclusions.

Adult↗
PubMed1996

Evidence of somatic mutations in osteoarthritis.

We examined, cytogenetically and by in situ hybridization (ISH) techniques, the synovia, osteophytes, and articular cartilage from 32 patients with pronounced osteoarthritis (OA), a prevalent form of arthropathy characterized by progressive reduction of articular cartilage, and synovial samples from 17 control patients. In short-term cultures, clonal chromosome aberrations, in particular the gain of chromosomes 7 (+7) and 5 (+5), were found to be strongly associated with OA. These aberrations were found in almost 90% of the cultures from synovia and osteophytes, whereas only 1/11 synovial samples from joints unequivocally unaffected by OA had cells with +5 or +7. The in vivo nature of trisomy 7 was demonstrated by ISH on uncultured cells, and serial passaging showed that cells with +7 had a proliferative advantage in vitro. Thus, the combined data indicate that cells with somatic mutations appear early and may be influential in the disease process leading to OA.

Adult↗
PubMed1996

Dichotomy of hyperdiploid acute lymphoblastic leukemia on the basis of the distribution of gained chromosomes.

From literature data on 3,149 cytogenetically abnormal cases of acute lymphoblastic leukemia (ALL) 1,118 clones with a gain of 1-11 chromosomes were retrieved. Within each subgroup of polysomy, the distribution of gained chromosomes was clearly nonrandom. In general, two different patterns were seen in ALLs with 1-5 and 6-11 extra chromosomes, respectively. In the former group, chromosomes X, 8, and 21 were consistently over-represented, and in the latter most or all polysomy subgroups contained an excess of chromosomes X, 4, 6, 10, 14, 17, 18, and 21. Chromosomes Y, 1-3, 5, 7, 9, 11-13, 15, 16, 19, and 20 were never significantly over-represented in any polysomy subgroup. The results of the present study confirm the nonrandom nature of chromosomal gain in ALL and suggest that when ALLs are to be subdivided into those with moderate and pronounced hyperdiploidy, the former should contain cases with 47-51 chromosomes and the latter those with 52-57 chromosomes.

Humans↗
PubMed1996

Chromosome rearrangements in synovial chondromatous lesions.

Short-term cultures from one synovial chondroma and three cases of synovial chondromatosis, a lesion for which no previous karyotypic information exists, were cytogenetically analysed. Whereas the chondroma displayed the relatively simple karyotype 46,XY,add(12)(q13),der(17)t(12;17)(q13;q21), more complex changes were found in the three cases of chondromatosis: case 1, 47,XY,der(1)inv(1)(p13q25)del (1)(q25q32), t(1;12)(q25;q13), + 5,der(12)add(12)(p11)t(1;12)(p22;q13); case 2, 47,XY,add(10)(q26), + 20/46 idem,-6/46,XY,t(2;4)(q33;q21), add(21)(p11); and case 3, 44,XY,add(1)(p36), del(1)(p13p22),add(6)(p25), del(7) (q22q32),del(10)(q21),add(11)(q13),-17,-18. The cytogenetic findings strongly suggest that synovial chondro-matosis is a clonal proliferation. Apart from a near-diploid chromosome number, the only recurrent cytogenetic features among the four cases were loss of band 10q26 and rearrangements of 1p13 and 12q13, found in two cases each. While chromosome bands 1p13 and 10q26 have not been reported to be involved in other types of benign chondromatous lesions, the 12q13-15 segment is recurrently rearranged in a variety of chondromatous tumours, e.g. pulmonary chondroid hamartomas. The present finding of translocations affecting band 12q13 in two of the cases emphasises that, irrespective of the anatomical localisation of the tumours, rearrangements of genes in 12q13-15 are important in the development of a large subset of benign and malignant cartilage-forming tumours.

Aged↗
PubMed1996

Fine needle aspiration (FNA) of synovial sarcoma--a comparative histological-cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination and DNA-ploidy analysis.

A retrospective study of 25 FNAs (11 aspirates from primary tumours and 14 from recurrencies and metastases) from 15 synovial sarcomas was performed. The cytological findings were correlated with the histopathology and the value of immunohistochemical and electron microscopic examination as well as DNA-ploidy and cytogenetic analysis for diagnosis were assessed. A reproducible cellular pattern with a reliable diagnosis of spindle cell sarcoma was possible provided that the aspirates were cell rich. However, a true biphasic pattern indicative of synovial sarcoma was only seen in one of the 25 specimens. Electron microscopic examination of the aspirates was a valuable adjunctive diagnostic method, whereas immunocytochemistry and DNA-ploidy analysis were not. Immunohistochemical, electron microscopic and cytogenetic analysis were all valuable ancillary methods when performed on surgical specimens. Malignant haemangiopericytoma and fibrosarcoma were the most important differential diagnoses in the FNA specimens.

Adult↗
PubMed1996

Combined morphologic and karyotypic study of 28 myxoid liposarcomas. Implications for a revised morphologic typing, (a report from the CHAMP Group).

Cytogenetic analysis carried out in 28 adipose tissue tumors diagnosed microscopically as myxoid liposarcoma (ML) revealed a t(12;16)(q13:p11) chromosomal translocation in 26 of the 28 cases. Morphologically, these tumors were subclassified into the following categories: well-differentiated, six cases: poorly differentiated round cell type, 17 cases: poorly differentiated spindle cell type, five cases. Poorly differentiated ML behaved in a more aggressive fashion than the well-differentiated tumors. The results of this study confirm the consistency and specificity of the t(12;16)(q13:p11) translocation as the genetic marker of ML, support the contention that liposarcomas with round cells belong to the ML category, and confirm Stout's proposal for the existence of a poorly differentiated ML composed of spindle cells. Cytogenetic analysis may be helpful in the differential diagnosis of ML with atypical lipomatous tumors, which is characteristically associated with ring and giant marker chromosomes, and of ML with lipoblastoma, which is typically associated with 8q alterations. The existence of a mixed ML-atypical lipomatous tumor remains questionable. The genetic events associated with the greater aggressiveness of the poorly differentiated types of ML remain to be determined.

Adult↗
PubMed1996

Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group).

Fifty-nine cases of atypical lipomatous tumors (ALT) of soft tissue (atypical lipomas, well-differentiated liposarcomas) were studied morphologically and cytogenetically as part of an international collaborative study. Forty-nine cases were deeply seated (including retroperitoneum), and 10 were superficial. Clonal chromosomal abnormalities were found in 55 cases (93%). Supernumerary ring or giant marker chromosomes (RGCs), the sole consistent alteration, were found in 37 ALTs (63%). They were more common in tumors that were large (p < 0.001), deeply seated (p < 0.005), that contained lipoblasts (p < 0.05), and that had marked cytologic atypia (p < 0.05). In a relatively short follow-up period (average, 3 years), only three of 59 cases recurred, one resulting in the patient's death. All three cases had RGCs. Also, five of the six cases that underwent dedifferentiation had RGCs, indicating that RGCs are associated not only with low-grade malignant behavior (in the form of local recurrence) but also with the potential for tumor progression. When the karyotypic profile of ALT was compared with that of 233 other types of adipose tissue tumors similarly analyzed by the authors, a statistically highly significant correlation (p < 0.0001) was found between ALT and RGCs. These results support the existence of ALT as a distinct tumor subtype that is different from ordinary lipoma and from spindle or pleomorphic lipoma, albeit histogenetically closely related to them. It also supports the proposed pathogenetic link between ALT and dedifferentiated liposarcoma. The association between chromosomal and morphologic findings indicates the potential role of karyotypic analysis in the differential diagnosis of ALT with ordinary lipoma, spindle or pleomorphic lipoma, hibernoma, and myxoid liposarcoma.

Adult↗
PubMed1996

Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group.

Soft tissue tumors commonly show cytogenetic abnormalities, some of which are tumor specific. Lipomatous tumors represent the largest category of soft tissue neoplasms, and numerous karyotypic aberrations have been identified. However, clear-cut correlation between morphology and karyotype has not been undertaken on a systematic basis in a double-blind setting. The morphological features and histological diagnosis of 178 lipomatous neoplasms were reviewed independently without knowledge of the clinical data. The consensus diagnoses were then correlated with the clinical findings and compared with the tumors' karyotypes, using G-banded preparations from short-term cultures. The data were collated by a multicenter collaborative group of pathologists, geneticists, and surgeons. Clonal chromosomal abnormalities were identified in 149 cases studied (84%) and, to a large extent, the karyotype correlated with the morphological diagnosis. Specifically, 26 (96%) of 27 myxoid liposarcomas and its poorly differentiated variants showed a t(12;16); 29 (78%) of 37 atypical lipomatous tumors (including 5 dedifferentiated cases) showed ring chromosomes; 74 (80%) of 93 subcutaneous and intramuscular lipomas had karyotypic aberrations affecting mainly 12q, 6p, and 13q; 7 of 8 spindle cell and pleomorphic lipomas had aberrations of 16q; 3 lipoblastomas showed 8q rearrangements; and 2 hibernomas showed 11q abnormalities. We conclude that cytogenetic abnormalities are common in lipomatous tumors, correlate reliably with morphological sub-type in many cases, and can be of diagnostic value in histologically borderline or difficult cases.

Adolescent↗