Dedifferentiation of a well-differentiated liposarcoma to a highly malignant metastatic osteosarcoma:

Forus, Anne; Larramendy, Marcelo L.; Meza‐Zepeda, Leonardo A.; Bjerkehagen, Bodil; Godager, Linda H.; Dahlberg, Anine B.; Sæter, Gunnar; Knuutila, Sakari; Myklebost, Ola

doi:10.1016/s0165-4608(00)00369-1

Cited by 49 publications

(17 citation statements)

References 39 publications

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“…Gains, highlevel amplifications, or both, of subregions of 1q and 12q are the imbalances that have been described most frequently. 2,3,9,10,16,17 The results of our analyses of 11 well-differentiated liposarcomas confirmed the findings of these earlier reports.…”

Section: Discussionsupporting

confidence: 91%

“…When located in the subcutis, they are usually cured by local surgical resection and rarely recur. 2 Comprising 40-45% of all liposarcomas, the well-differentiated liposarcomas are thus the largest subgroup of adipocytic malignancies. Cytogenetic characteristics of well-differentiated liposarcomas are rings as well as giant marker chromosomes that contain amplified genetic material derived from chromosome region 12q13-q15 and, alternatively, additional material from chromosomes 1, 4, and 16.…”

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confidence: 99%

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Gains of 13q are correlated with a poor prognosis in liposarcoma

et al. 2005

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Liposarcomas are a phenotypical heterogenous group of tumors divided into four main subtypes: welldifferentiated, dedifferentiated, myxoid/round cell, and pleomorphic. The aim of this study was to compare DNA sequence copy number changes of these subtypes as investigated by comparative genomic hybridization in 36 patients. Comparative genomic hybridization revealed genomic imbalances in tumors of 27 patients (mean 5.6 imbalances per tumor). The most frequent gains were within single regions of 1q, 12q, and 13q. We found a significant correlation of poor overall survival and gain of 13q21 (P ¼ 0.0221), 13q22 (P ¼ 0.0341), 13q31 (P ¼ 0.0410), and 13q32 (P ¼ 0.0074). The univariate Cox regression analysis revealed an increased risk of tumorrelated death for patients whose liposarcomas possess with gains of 13q21 and 13q32 simultaneously (P ¼ 0.010; RR ¼ 7.1; 95% CI 1.6-31.7). Furthermore, 12 high-level amplifications were found in tumors of seven patients. In four cases 12q14-q15 and in two cases 13q32-q33 were amplified. We identified in different liposarcoma subtypes characteristic genomic changes: Gains and high-level amplifications of 12q occurred in all 11 investigated well-differentiated liposarcomas, and these changes were often present simultaneously with gains of 1q (mean 5.5 changes). In the two dedifferentiated liposarcomas, gains of 1q in both liposarcomas, and a high-level amplification of 13q were striking. Only eight of the 17 patients with myxoid/round cell liposarcomas showed changes in DNA copy number (mean 3.4 imbalances). In four of these eight cases gains of 13q occurred. The six pleomorphic liposarcomas possessed the most frequent genomic imbalances (mean number 16.3) of all liposarcoma subtypes investigated. These imbalances were in almost all chromosomal regions detected predominantly as over-representations of chromosomes 1, 5p, 13q, and 22q. Summarizing, all subtypes but well-differentiated liposarcomas showed gains of 13q, which were associated with a poor prognosis. Modern Pathology (2005) 18, 638-644, advance online publication, 12 November 2004; doi:10.1038/modpathol.3800326Keywords: CGH; gain of 13q; liposarcoma subtypes; poor prognosis Liposarcomas are the most common soft-tissue sarcomas in adults and account for approximately 20% of all mesenchymal malignancies. The WHO classification divides liposarcomas into four main histological subtypes that are correlated with degree of malignancy: well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic liposarcomas. 1 Well-differentiated liposarcomas are tumors of low degree of malignancy. When located in the subcutis, they are usually cured by local surgical resection and rarely recur. 2 Comprising 40-45% of all liposarcomas, the well-differentiated liposarcomas are thus the largest subgroup of adipocytic malignancies. Cytogenetic characteristics of well-differentiated liposarcomas are rings as well as giant marker chromosomes that contain amplified genetic material derived from chromosome region 12q13-q15 and, alternative...

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

Gains of 13q are correlated with a poor prognosis in liposarcoma

et al. 2005

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“…Both well-differentiated and dedifferentiated liposarcoma are characterized cytogenetically by ring or giant marker chromosomes derived from amplified 12q13-15 material, with additional aberrations more often detected in dedifferentiated variants. [13][14][15] Indeed, it was demonstrated recently that a subgroup of previously diagnosed malignant fibrous histiocytoma, especially for those arising in the retroperitoneum, is genetically similar with well-differentiated/dedifferentiated liposarcoma family. 13,14 Although dedifferentiation is associated with a six-fold increased risk of death as compared with well-differentiated histology, 16 some authors believe that dedifferentiated liposarcoma has a low incidence of distant metastasis, ranging from 1 to 18% in various series.…”

Section: Discussionmentioning

confidence: 99%

Distant metastasis in retroperitoneal dedifferentiated liposarcoma is rare and rapidly fatal: a clinicopathological study with emphasis on the low-grade myxofibrosarcoma-like pattern as an early sign of dedifferentiation

et al. 2005

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The metastatic incidence of retroperitoneal dedifferentiated liposarcoma is comparatively lower than other pleomorphic sarcomas, varying widely from 1 to 18%. Low-grade dedifferentiation resembling low-grade fibrosarcoma has been recently accepted as part of the morphologic spectrum of dedifferentiated liposarcoma and was reported to have similar metastatic and survival rates to its high-grade counterpart. We sought to determine the metastatic incidence of retroperitoneal dedifferentiated liposarcoma, the clinicopathological features related to metastasis, and their postmetastatic behavior. Of all 354 retroperitoneal liposarcoma cases diagnosed at Memorial Sloan-Kettering Cancer Center during 1982-2003, we identified seven patients developing distant metastases, occurring in four females and three males, ranging from 35 to 73 years in age at presentation. They were all de novo dedifferentiated, while none of the well-differentiated liposarcoma or secondary dedifferentiated liposarcoma developed distant metastasis. Primary tumor sizes varied from 7.5 to 25 cm. All seven patients developing metastases contained Z50% dedifferentiated elements in the primary tumor, with a predominant morphology resembling myxofibrosarcoma in five cases. The metastatic sites included the lung in four patients, somatic soft tissue in two, and liver in one. The median metastasis-free survival was 48 months, with only two patients experiencing local recurrences before developing metastasis. Six patients died of disease at median follow-up of 53 months after diagnosis and only 5 months after their first metastases. In conclusion, retroperitoneal dedifferentiated liposarcoma have a low metastatic rate, which is strongly related to de novo dedifferentiated histology that usually constitutes a prominent component of the primary tumor. Irrespective of the grade dedifferentiated liposarcoma with myxofibrosarcoma-like features should be closely monitored. Once metastases occur, they tend to follow a rapidly fatal course. Modern Pathology (2005) 18, 976-984.

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“…FISH hybridisation to interphase nuclei Slides were treated as described (Forus et al, 2001), hybridisation and washes were according to standard procedures. Fluorescein isothiocyanate (FITC)-conjugated sheep anti-digoxygenin (Boehringer Mannheim, Germany) followed by FITC-or ALEXA 488-labelled donkey anti-sheep (Molecular Probes, Leiden, The Netherlands) was used for detection of digoxigenin, andavidin-conjugated Cy3 (Amersham Life Science, Little Chalfont, UK) for detection of biotin.…”

Section: Fluorescent In Situ Hybridisation (Fish) To Interphase Nucleimentioning

confidence: 99%

“…Detection of signals was done by tyramide ampli®cation (TSA-Indirect kit for ISH, NEN, Boston, MA, USA) followed by a streptavidine-FITC antibody (NEN, Boston, MA, USA) (Forus et al, 2001).…”

Section: Fluorescent In Situ Hybridisation (Fish) To Interphase Nucleimentioning

confidence: 99%

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

et al. 2001

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PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly ampli®ed in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired a nity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found ampli®cation of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant ®brous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE ampli®cation was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE ampli®cation developed metastases. A similar situation was observed in all breast carcinomas with ampli®cation of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, ampli®-cation and overexpression of PRUNE has the same e ect in the tumours. We suggest that ampli®cation and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that a ect the development or progression of these tumours. Oncogene (2001) 20, 6881 ± 6890.

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Dedifferentiation of a well-differentiated liposarcoma to a highly malignant metastatic osteosarcoma:

Cited by 49 publications

References 39 publications

Gains of 13q are correlated with a poor prognosis in liposarcoma

Gains of 13q are correlated with a poor prognosis in liposarcoma

Distant metastasis in retroperitoneal dedifferentiated liposarcoma is rare and rapidly fatal: a clinicopathological study with emphasis on the low-grade myxofibrosarcoma-like pattern as an early sign of dedifferentiation

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

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