Malgorzata Jaworska

Patterns of chromosomal imbalances in benign solitary fibrous tumours of the pleura.

Abstract Solitary fibrous tumours (SFTs) of the pleura, in contrast to malignant mesothelioma, occur independently of previous asbestos exposure. They are benign tumours, but may recur if the stalk to the adjacent pleural or lung tissue remains in situ during surgical removal. The molecular pathology of SFTs is largely unknown. We used comparative genomic hybridisation (CGH) to characterise 12 localised SFTs and 12 predominantly sarcomatoid mesotheliomas. Fifty-eight percent of the investigated SFTs did not show any chromosomal imbalances. The most frequent defects were losses on chromosome arms 13q (33%), 4q and 21q (17% each). Significant gains were seen at chromosome 8 and at 15q in two cases each. There was no correlation between tumour size and molecular pathology findings. In contrast, 75% of the mesotheliomas carried chromosomal defects. On average, the mesotheliomas showed over three times as many defects per tumour as the SFTs. Localisation of several frequent losses and gains were similar to those of the SFTs. Therefore, in individual cases, a clear distinction between SFTs and sarcomatoid mesotheliomas is not possible based on CGH analysis alone. Further molecular characterisation of this rare tumour entity will be necessary to elucidate possible genes involved in early tumorigenesis.

Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic hybridization of 90 cases.

It is established that subtypes of human malignant mesotheliomas (MM) are associated with different survival times. Ninety cases of MM were examined using DNA cytometry and comparative genomic hybridization (CGH), with emphasis on the main histological subtypes; epithelioid, sarcomatoid and biphasic. A comparison by DNA cytometry revealed moderate differences, with the rare subgroup of mesodermomas having the highest and the sarcomatoid group the lowest rate of aneuploidy. Using CGH, 6.2 chromosomal imbalances per case on average could be detected. Losses (4.1/case) were more common than gains of chromosomal material (2.1/case). MM show no single, specific defect, but a typical pattern of genomic defects can be attributed to this tumour entity. Common losses are clustered at the chromosomal regions 9p21 (34%), 22q (32%), 4q31–32 (29%), 4p12–13 (25%), 14q12–24 (23%), 1p21 (21%), 13q13–14 (19%), 3p21, 6q22, 10p13–pter and 17p12–pter (16% each). Common gains are located on 8q22–23 (18%), 1q23/1q32 (16%), 7p14–15 and 15q22–25 (14% each). While differences in the frequencies of the defects between epithelioid and sarcomatoid MM are not as pronounced as are seen with the pleomorphic mesodermomas, several chromosomal locations (3p, 7q, 15q, 17p) show significant variations. The most pronounced distinguishing feature of sarcomatoid MM is a more than fourfold higher number of amplicons. These data indicate that MM has a distinctive tumour biology with a broad spectrum of heterogeneity, as reflected in morphology and also, more subtly, in the patterns of chromosomal imbalances of the subtypes. Copyright

Effect of KRAS codon13 mutations in patients with advanced colorectal cancer (advanced CRC) under oxaliplatin containing chemotherapy. Results from a translational study of the AIO colorectal study group

BackgroundTo evaluate the value of KRAS codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines.MethodsTumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS).Results201 patients were analysed for KRAS mutation (61.2% males; mean age 64.2 ± 8.6 years). KRAS mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three KRAS genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens.ConclusionsOur data suggest that the type of KRAS mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important.Trial registration number2002-04-017

[Myoepithelioma of soft tissue -- case report with clinicopathologic, ultrastructural, and cytogenetic findings].

The case of a soft tissue myoepithelioma is presented including clinicopathologic, ultrastructural, and genetic findings. A 30-year-old male patient suffered from a soft tissue tumor within the deep soft tissues of the right lower leg measuring 13.2 x 8.2 x 9 cm. Histologically, the lesion was diagnosed as a myoepithelioma displaying a lobulated architecture with cords and nests of epithelioid and spindle cells without cytologic atypia lying within a fibromyxoid and partly chondroid matrix; immunohistochemistry was positive for pancytokeratin, S100-protein, calponin and partly for GFAP and EMA. Ultrastructural analysis revealed glycogen deposits and cell-membrane-associated plaque structures, whereas true myofilaments could not be identified (with immunohistochemistry being negative for actin). Using comparative genomic hybridization (CGH), a gain of chromosome Y was detected. A loss on 17p could not be detected unambiguously. However, based on the low resolution of CGH a small loss cannot be excluded. The patient was free of disease 25 months following complete tumor resection. Myoepitheliomas/mixed tumors of deep soft tissue represent rare soft tissue lesions that may reach a considerable size and may mimic other soft tissue tumors or sarcomas. Based on a local relapse rate of approximately 20% according to the literature, a complete resection with thorough follow-up should be recommended.

Myoepitheliom des Weichgewebes

The case of a soft tissue myoepithelioma is presented including clinicopathologic, ultrastructural, and genetic findings. A 30-year-old male patient suffered from a soft tissue tumor within the deep soft tissues of the right lower leg measuring 13.2 x 8.2 x 9 cm. Histologically, the lesion was diagnosed as a myoepithelioma displaying a lobulated architecture with cords and nests of epithelioid and spindle cells without cytologic atypia lying within a fibromyxoid and partly chondroid matrix; immunohistochemistry was positive for pancytokeratin, S100-protein, calponin and partly for GFAP and EMA. Ultrastructural analysis revealed glycogen deposits and cell-membrane-associated plaque structures, whereas true myofilaments could not be identified (with immunohistochemistry being negative for actin). Using comparative genomic hybridization (CGH), a gain of chromosome Y was detected. A loss on 17p could not be detected unambiguously. However, based on the low resolution of CGH a small loss cannot be excluded. The patient was free of disease 25 months following complete tumor resection. Myoepitheliomas/mixed tumors of deep soft tissue represent rare soft tissue lesions that may reach a considerable size and may mimic other soft tissue tumors or sarcomas. Based on a local relapse rate of approximately 20% according to the literature, a complete resection with thorough follow-up should be recommended.

Myoepitheliom des Weichgewebes@@@Myoepithelioma of soft tissue — case report with clinicopathologic, ultrastructural, and cytogenetic findings: Fallbericht mit klinisch-pathologischen, ultrastrukturellen und zytogenetischen Befunden

The case of a soft tissue myoepithelioma is presented including clinicopathologic, ultrastructural, and genetic findings. A 30-year-old male patient suffered from a soft tissue tumor within the deep soft tissues of the right lower leg measuring 13.2 x 8.2 x 9 cm. Histologically, the lesion was diagnosed as a myoepithelioma displaying a lobulated architecture with cords and nests of epithelioid and spindle cells without cytologic atypia lying within a fibromyxoid and partly chondroid matrix; immunohistochemistry was positive for pancytokeratin, S100-protein, calponin and partly for GFAP and EMA. Ultrastructural analysis revealed glycogen deposits and cell-membrane-associated plaque structures, whereas true myofilaments could not be identified (with immunohistochemistry being negative for actin). Using comparative genomic hybridization (CGH), a gain of chromosome Y was detected. A loss on 17p could not be detected unambiguously. However, based on the low resolution of CGH a small loss cannot be excluded. The patient was free of disease 25 months following complete tumor resection. Myoepitheliomas/mixed tumors of deep soft tissue represent rare soft tissue lesions that may reach a considerable size and may mimic other soft tissue tumors or sarcomas. Based on a local relapse rate of approximately 20% according to the literature, a complete resection with thorough follow-up should be recommended.