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PubMed1996

Liposarcoma: outcome and prognostic factors following conservation surgery and radiation therapy.

PURPOSE: Liposarcoma is among the more common types of soft-tissue sarcoma. This retrospective review was performed to determine the outcome and delineate prognostic factors for this disease when treated by conservation surgery and radiation. METHODS AND MATERIALS: Between 1964 and 1992, 112 consecutive patients with liposarcoma were treated with conservation surgery and radiotherapy. Univariate and multivariate statistics were used to evaluate the outcome with local control, metastatic relapse, and survival as end points, and to delineate independently significant prognostic factors. RESULTS: Preoperative radiation to a mean dose of 50 Gy was used in 36 patients and postoperative radiation to a mean dose of 61 Gy was used in 76 patients. At a median follow-up of 9 years (range 2-25), 34 patients (30%) developed disease progression at some site. Local recurrence developed in 14 patients (13%), and the actuarial local relapse rate was 13% at 10 years. Metastases developed in 23 patients (21%) with an actuarial metastatic rate of 23% at 10 years. Five-, 10-, and 15-year survival rates were 79%, 69%, and 61%, respectively. The most important factor influencing outcome--whether local control, metastases, or survival--was tumor histologic subtype. Well-differentiated (15 patients) and myxoid (including round cell) (71 patients) subtypes had a local control rate exceeding 90% at 10 years. No patient with well-differentiated liposarcoma developed metastases. The actuarial metastatic rate for myxoid tumors was 22% at 10 years and was higher for large than small tumors. The pattern of metastases for this variant was atypical with a preponderance of extrapulmonary sites. Pleomorphic liposarcoma (26 patients) was a highly malignant tumor with a high local recurrence rate of 37% and a metastatic rate of 41% at 10 years. Larger pleomorphic tumors had a significantly higher metastatic rate than smaller ones. These biologic factors were reflected in progressively decreasing 10-year survival rates from 87% for well-differentiated lesions, through 76% for myxoid tumors, to 39% for pleomorphic tumors. Although other factors such as positive resection margins and prior local recurrence were also independently significant determinants of outcome, histology was the overriding factor. CONCLUSION: Liposarcoma is a highly pleomorphic disease whose outcome is greatly determined by its histologic subtype: so greatly that results reported without histologic stratification are likely meaningless. Conservation surgery and radiation achieve excellent local results and with relatively little metastatic risk for patients with well-differentiated and myxoid liposarcomas. The same treatment strategy appears appropriate for pleomorphic liposarcoma, but with a much smaller expectation of a satisfactory outcome. The development of effective systemic therapy is an important goal for this variant of liposarcoma.

Adolescent↗

PubMed2000

Liposarcoma of the pleural cavity: clinical and pathologic features of 4 cases with a review of the literature.

BACKGROUND: Primary liposarcomas of the pleura are extremely rare malignancies, and relatively few reports appear in the world literature. DESIGN: We compiled a small series of 4 cases of primary pleural liposarcoma from the files of the Armed Forces Institute of Pathology (Washington, DC) and compared the histopathologic and clinical features of these 4 cases with those of 9 previously published cases. RESULTS: Our investigation included the case studies of 9 men and 4 women, aged 19 to 80 years (average, 49 years). Histologic subtypes in the 9 cases with available information included 5 myxoid liposarcomas, 1 well-differentiated liposarcoma, and 3 liposarcomas with mixtures of histologic types. Surgical resection with or without chemotherapy appeared to be the most common form of treatment, although radiation therapy was used in some cases and seemed beneficial. Survival information was available for 11 cases; 4 patients died of disease at 7, 9, 12, and 19 months; 1 died of heart failure 2 days after presentation; 1 died of unknown causes 16 months after presentation; and 3 patients were alive without tumor at 5, 16, and 66 months after diagnosis. One patient had local recurrence at 2 years. A second surgical resection in this patient failed, and he died of disease 9 years after initial presentation. A second patient experienced recurrence at 4 years and was free of disease 4 years after the second surgical resection. CONCLUSIONS: Primary pleural liposarcomas occur predominantly in older men, and the myxoid histologic subtype is the most common. Radiographic or surgical evaluation is important to distinguish primary pleural liposarcoma from chest wall or mediastinal sarcomas, as well as metastases from other sites. Although further investigation is needed, evidence from the cases reviewed here indicates that surgical resection with adjuvant radiation therapy may benefit patients with primary pleural liposarcoma.

Aged↗

PubMed1999

Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up.

BACKGROUND: Liposarcoma is one of the most common histologic types of soft tissue sarcoma and presents a wide spectrum of clinical behavior. The authors examined the correlation among histologic subtypes, outcomes, and patterns of recurrence among patients with extremity liposarcomas. METHODS. A retrospective review of all patients with intermediate and high grade extremity liposarcoma referred to the University of Texas M. D. Anderson Cancer Center from January 1, 1980, to December 31, 1992, was performed. Data on clinical presentation, treatment, patterns of treatment failure, and outcome were evaluated. RESULTS: During the 13-year study period, 122 patients with intermediate or high grade extremity liposarcoma were identified: 102 patients (84%) with myxoid subtype, 18 patients (15%) with pleomorphic subtype, and 2 patients (2%) with mixed histology. There were no differences between the myxoid and pleomorphic subtype groups in tumor size (T1 vs. T2), depth in relation to the muscular fascia, or anatomic site. The median follow-up was 70 months. The 5-year overall survival rate for all intermediate and high grade extremity liposarcoma patients presenting with primary disease (n=85) was 74%; the 5-year local recurrence free survival, distant recurrence free survival, and disease free survival rates were 93%, 78%, and 73%, respectively. Among the 102 patients with myxoid tumors, 33 had distant recurrences; 31 of these were to extrapulmonary soft tissue sites (e.g., the retroperitoneum, chest wall, pleura, pericardium, pelvic sidewall, and soft tissue of the back), and 2 were to the lung only. Among the 18 patients with pleomorphic tumors, 10 had distant recurrences; 3 occurred at extrapulmonary sites, and 7 occurred in the lung only (P < 0.05 for myxoid vs. pleomorphic subtypes). CONCLUSIONS: Myxoid liposarcomas often metastasized to extrapulmonary sites and did so significantly more frequently than pleomorphic tumors. Imaging of the abdomen, retroperitoneum, and extrapleural chest should be performed for accurate staging and posttreatment follow-up of patients with myxoid liposarcoma. Patients presenting with "primary" myxoid liposarcoma of the trunk should be carefully evaluated for an occult primary tumor in an extremity.

Adolescent↗

PubMed1999

Cytomorphologic features of fine-needle aspiration of liposarcoma.

The cytomorphologic features of fine-needle aspirates (FNA) of liposarcomas have not been fully characterized. In the current study, we attempted to identify cytological attributes of liposarcoma in FNA. Twelve FNAs of histologically proven liposarcomas were used for this study. They included 10 myxoid and two well-differentiated liposarcomas. Four cytological criteria were chosen for evaluation. These included a complex capillary network, increased cellularity, the presence of a metachromatic stroma for myxoid liposarcoma, and finally the identification of lipoblasts. Eighteen FNAs of lipomas and 17 FNAs of nonlipomatous soft-tissue sarcomas were used as controls for evaluation of the same features. The diagnosis of liposarcoma had been rendered on FNA in 7 cases (58%). The diagnosis was suggested in 3 cases (25%), and a suggestion of sarcoma was rendered in 2 cases. Complex capillary networks were identified in 9 of 12 cases (75%); this was seen in 8 of the 10 myxoid liposarcomas and 1 of the 2 well-differentiated neoplasms. Increased cellularity was seen in 7 of 12 cases (58%), metachromatic stroma was seen in 3 of 12 cases (25%), and lipoblasts were identified in 4 of 12 cases (33%). None of the lipomas or sarcomas exhibited a complex capillary network. When capillaries were identified in lipomas, they were straight, with minimal branching. The lipomas did not show evidence of increased cellularity in any cases. Metachromatic stroma was more frequently seen in the nonlipomatous sarcomas than in the liposarcomas. No lipoblasts were identified in any of the control FNAs.

Adult↗

PubMed1989

The prognostic value of histologic subtypes in primary extremity liposarcoma.

Patients with a localized primary liposarcoma of the extremity who were treated in Memorial Sloan-Kettering Cancer Center between 1968 and 1978 were studied. The prognosis of patients with extremity liposarcoma was analyzed according to histopathologic subtypes. A system of five subtypes was used; well-differentiated, myxoid, fibroblastic, lipoblastic, and pleomorphic liposarcomas. The 5-year treatment failure rates and survival rates were, respectively, 30% and 100% for well-differentiated, 25% and 88% for myxoid, 60% and 58% for fibroblastic, 100% and 40% for lipoblastic, and 64% and 56% for pleomorphic liposarcomas. Although local recurrence was present in all five subtypes, a significant increment in local failure was seen in patients with high-grade liposarcomas. Distant metastasis after the initial operation was not found in patients with well-differentiated liposarcoma and rare in the patients with myxoid liposarcoma. In contrast, 50% of the patients with fibroblastic, lipoblastic, and pleomorphic liposarcoma had a distant relapse within 5 years.

Adolescent↗

PubMed2005

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.

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 >or=50% 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.

Adult↗

PubMed2001

MDM2+/CDK4+/p53+ oral liposarcoma: case report and review of the literature.

Although liposarcoma is one of the most common soft tissue sarcomas, its location in the oral cavity is very rare. To our knowledge, only 43 cases of liposarcoma originating in the oral tissues have been reported in the English-language literature. In this article, we report a case of well-differentiated liposarcoma affecting the cheek of a 28-year-old man and review the oral liposarcoma literature. Immunohistochemical analysis of the tumor revealed an MDM2+/CDK4+/p53+ immunophenotype that is consistent with the immunohistochemical profile of well-differentiated liposarcoma originating in other areas of the body. Quantitative polymerase chain reaction analysis of the DNA levels of the MDM2 (human homologue of the murine double-minute type 2), CDK4 (cyclin-dependent kinase 4), and SAS (sarcoma amplified sequence), genes was performed, revealing only SAS gene amplification. The possibility of misdiagnosis of oral liposarcoma because of its sometimes inconspicuous clinical and microscopic features is emphasized. Careful pathologic examination of liposarcoma is essential for discrimination from benign adipose tissue neoplasms and for precise histologic classification, both of major prognostic significance. Possible implications of molecular and cytogenetic analysis for unraveling the pathogenesis and determining the prognosis of liposarcoma are discussed.

Adult↗

PubMed2006

A novel germline mutation of MSH2 in a hereditary nonpolyposis colorectal cancer patient with liposarcoma.

BACKGROUND: One of the clinical features of hereditary nonpolyposis colorectal cancer (HNPCC) is a high incidence of multiple primary neoplasms arising in various organs including the gastrointestinal and genitourinary tracts. Among extracolonic tumors, a limited number of soft tissue sarcomas associated with HNPCC have been reported, and the mechanism underlying liposarcoma in HNPCC patients remains unclear. AIM: We herein report the case of a HNPCC patient with liposarcoma, with the goal of elucidating the involvement of a mismatch repair deficiency in the tumor. METHODS AND RESULTS: A 40-yr-old Japanese patient, who had a past history of adenocarcinoma of the rectum and transitional cell carcinoma of the urinary bladder, developed a liposarcoma in his left thigh. Although his family history did not fulfill the revised Amsterdam criteria, his blood sample was subjected to genetic testing. Direct sequencing of the genomic DNA from the blood identified an AT deletion at codon 677 in exon 13 of hMSH2, a pathogenic mutation that has not been reported before. The expression of MSH2 in the liposarcoma and rectal cancer of the patient was analyzed by immunohistochemistry, which revealed loss of MSH2 expression in the tumors. To investigate whether the loss of MSH2 was a common feature of liposarcoma, we examined the MSH2 expression in an additional two sporadic liposarcomas, both of which were stained with anti-MSH2 antibody. CONCLUSION: We identified a novel pathogenic germline mutation of MSH2 in an HNPCC patient. Since an immunohistochemical analysis showed no nuclear staining for MSH2 protein in the liposarcoma as well as the rectal cancer, the loss of wild-type MSH2 protein was thus considered to possibly play a role in the development of liposarcoma in HNPCC patients.

Adult↗

PubMed1993

Liposarcoma of the extremities: MR and CT findings in the histologic subtypes.

The findings on images of liposarcomas of the extremities in 48 patients (26 men and 22 women aged 20-85 years) were reviewed to correlate the histologic subtypes with radiologic appearance. Computed tomographic scans were obtained in 36 patients; magnetic resonance (MR) images, in 27 patients. The study group had 19 myxoid, 12 well-differentiated, nine round cell, and eight pleomorphic liposarcomas. Well-differentiated liposarcomas were predominantly composed of fat, typically with thick septa, which were hyperintense on T2-weighted spin-echo MR images. The heterogeneity of tumor helped differentiate tumor subtypes. Eleven of 19 myxoid tumors were mildly heterogeneous. Round cell and pleomorphic subtypes, which tend to be aggressive, were generally heterogeneous. Well-differentiated liposarcomas may be confidently differentiated from other subtypes of liposarcoma. Except for the well-differentiated subtypes, liposarcomas often contain no fat. Moderate to marked heterogeneity is common in high-grade liposarcomas; myxoid liposarcomas tend to be homogeneous and may mimic cysts.

Adult↗

PubMed2003

Differential diagnosis of benign peripheral lipoma from well-differentiated liposarcoma on MR imaging: is comparison of margins and internal characteristics useful?

OBJECTIVE: Our objective was to evaluate the reliability of MR imaging in distinguishing between benign lipoma and well-differentiated liposarcoma. MATERIALS AND METHODS: The MR images of 35 pathologically proven benign lipomas in 35 patients and 23 well-differentiated liposarcomas in 17 patients were retrospectively reviewed. T1-, T2-, and fat-suppressed T1-weighted images were obtained after administration of gadopentetate dimeglumine. Margins and internal characteristics revealed on the MR images and the degree of contrast enhancement of septa were evaluated. These MR imaging findings were compared for well-differentiated liposarcomas and benign lipomas. RESULTS: Completely irregular margins were recognized only in benign lipomas with a pathologic diagnosis of infiltrating lipoma. All tumors without a recognizable nonadipose component were benign lipomas (p < 0.05). As for the well-differentiated liposarcomas, thick septa and nodular or patchy nonadipose components were present more frequently in deep and retroperitoneal lesions than in subcutaneous lesions (p < 0.01). No cases showed only thin septa in the deep lesions of well-differentiated liposarcoma, and all cases showed thick septa or nodular or patchy nonadipose components. The septa in well-differentiated liposarcomas enhanced more strongly than did those in benign lipomas. The septa showed no enhancement relative to muscle in 11 of 19 benign lipomas, whereas the septa showed moderate or marked enhancement in all well-differentiated liposarcomas (p < 0.01). CONCLUSION: Careful assessment of margins and internal characteristics on MR imaging can be a useful aid in further distinguishing between biologically different benign lipoma and well-differentiated liposarcoma.

Adult↗

PubMed2004

Lipomas, lipoma variants, and well-differentiated liposarcomas (atypical lipomas): results of MRI evaluations of 126 consecutive fatty masses.

OBJECTIVE: Our objectives were to evaluate the reliability of MRI in distinguishing simple lipomas, lipoma variants, and well-differentiated liposarcomas (atypical lipomas) and to identify various imaging mimics of well-differentiated liposarcoma. MATERIALS AND METHODS: One hundred twenty-six consecutively imaged grossly fatty masses were retrospectively reviewed. MRI examinations, their prospective interpretations, and their corresponding pathology reports were compared to determine the reliability of MRI in distinguishing simple lipomas, lipoma variants, and well-differentiated liposarcomas. RESULTS: The success of MRI in identifying well-differentiated liposarcomas among other fatty masses was as follows: sensitivity, 100%; specificity, 83%; accuracy, 84%; positive predictive value, 38%; and negative predictive value, 100%. MRI was 100% specific in the diagnosis of simple lipoma. Sixty-three percent of lesions considered suspicious for well-differentiated liposarcoma were actually simple lipomas (13%) and benign lipoma variants (50%), including chondroid lipoma (13%), osteolipoma (6%), hibernoma (6%), lipoleiomyoma (6%), angiolipoma (6%), and infarcted lipoma (13%). CONCLUSION: Because of differences in treatment, prognosis, and long-term follow-up, it is important to preoperatively distinguish simple lipomas from well-differentiated liposarcomas. MRI is highly sensitive in the detection of well-differentiated liposarcomas and highly specific in the diagnosis of simple lipomas. However, when an extremity or body wall lesion is considered suspicious for well-differentiated liposarcoma, it is more likely (64%) to represent one of many benign lipoma variants.

Adult↗

PubMed1998

No correlation of c-myc overexpression and p53 mutations in liposarcomas.

Although it is well known that oncogenesis is a multistep process involving the activation of normal cellular genes to become oncogenes and/or the inactivation of tumor suppressor genes, this process has seldom been investigated in soft tissue tumours. We screened a group of 36 liposarcomas for genetic abnormalities in the p53 tumour suppressor gene and c-myc oncogene. Altered c-myc gene expression was examined by differential RT-PCR assay. p53 Gene mutations in exons 4-8 were analysed by using PCR-SSCP analysis and direct sequencing. Elevated c-myc expression was found in 6 of 31 liposarcomas (19.4%). p53 Gene mutations were observed in 5 of 36 liposarcomas (13.9%). Both genetic alterations were associated with the histological subtype of liposarcomas. Whereas c-myc gene expression was a characteristic of myxoid/round cell liposarcomas, p53 gene mutations were found more frequently in pleomorphic variants. Liposarcomas of the well-differentiated subtype showed neither p53 gene mutations nor altered c-myc gene expression. Our results indicate that the c-myc oncogene and the p53 tumor suppressor gene do not seem to cooperate in the oncogenesis of liposarcomas.

Adult↗

PubMed1997

Round cell liposarcoma with the insertion (12;16)(q13;p11.2p13).

Cytogenetic analysis of a short-term culture from a round cell liposarcoma revealed ins(12;16)(q13;p11.2p13) as a sole abnormality in all metaphase cells studied. This chromosome rearrangement, thus far not described in liposarcomas, leads to recombination of bands 12q13 and 16p11.2 and, thus, seems to be the equivalent of t(12;16)(q13;p11), a translocation that is highly specific for the myxoid type of liposarcoma. Our case represents the fourth fully karyotyped round cell liposarcoma that displays a cytogenetic rearrangement of bands 12q13 and 16p11, thus supporting the concept that round cell liposarcoma is related to myxoid liposarcoma and constitutes its poorly differentiated form. The fact that ins(12;16) was the only detectable chromosome aberration suggests that the presence of secondary cytogenetic aberrations is not a prerequisite for the development of a round cell histology in liposarcoma.

Adult↗

PubMed1997

Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms.

Recent findings have indicated that TP53 inactivation in sarcomas may result from mutation and/or deletion of the TP53 gene or, alternatively, from binding to the MDM2 gene products. To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry. Nineteen cases of the same series were also molecularly analysed for both MDM2 gene amplification and TP53 mutations, and a further ten cases for non-random chromosomal abnormalities. In the retroperitoneal well-differentiated-dedifferentiated (WD-DD) group, 15/16 WD and 8/8 DD liposarcomas displayed the mdm2+/p53+ phenotype, consistent with MDM2 gene amplification in the absence of TP53 mutations. In the non-retroperitoneal WD-DD group, 5/11 WD liposarcomas also retained the mdm2+/p53+ phenotype whereas all DD liposarcomas showed an immunophenotype and, when assessed, a genotype consistent with mutant TP53. Null mdm2 immunophenotype, coupled with evidence of a specific chromosome translocation t(12;16), was constantly observed in both the usual and the cellular subtypes of myxoid liposarcoma, three cases of which also showed TP53 alterations at the genetic or protein level. Neither mdm2 nor p53 overexpression was observed in the lipomas. The results show the existence of three main pathogenetically distinct groups of liposarcoma. The first retroperitoneal WD-DD group, which represents a novel class of tumours within a single histological category of sarcoma, where MDM2-mediated inactivation of p53 could be related to the pathogenetic mechanism. The second is the non-retroperitoneal WD-DD group, where the TP53 mutations appear to correlate with the dedifferentiation process. The third is the myxoid group, which is characterized by its own unique cytogenetic profile and never shows any involvement of TP53 or MDM2 genes. As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas.

Adolescent↗

PubMed1997

Molecular abnormalities of the p53 pathway in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma represents a distinct subtype of liposarcoma and is characterized by the presence of abrupt transition from well-differentiated liposarcoma to high-grade pleomorphic sarcoma (mostly MFH-like). A key role for p53 in tumour progression of this subset of liposarcomas has been suggested on the basis of p53 immunopositivity. A series of 14 dedifferentiated liposarcomas has been investigated by analysing the p53 gene and protein together with the p53-related molecules p21Waf1 and mdm2, to verify whether the p53 pathway is involved in the development and progression of this tumour type. The results indicate that the p53 gene is rarely involved in dedifferentiated liposarcoma (7 per cent of cases analysed) and that low percentages of p53 immunopositivity are still compatible with integrity of the p53 gene. This concept is also supported by the observed preservation of p21Waf1 immunoreactivity in all but the p53-mutated cases. By contrast, mdm2 overexpression emerges as the most frequent abnormality in dedifferentiated liposarcoma (57 and 78 per cent of cases in well-differentiated and high-grade areas, respectively).

Cell Differentiation↗

PubMed1998

Molecular abnormalities in liposarcoma: role of MDM2 and CDK4-containing amplicons at 12q13-22.

It has recently been shown that mdm2 overexpression with stabilization of p53 represents a characteristic of retroperitoneal well-differentiated-dedifferentiated, here renamed evolved (WD-E), liposarcomas at the immunocytochemical, molecular, and cytogenetic level. This make-up appears to be confined to half the cases in non-retroperitoneal well-differentiated liposarcomas. Since in different tumours MDM2 amplification involves amplicons encompassing flanking genes, such as CDK4, the possibility was investigated that in these tumours, CDK4 could act as an alternative or additional gene involved in the transformation mechanism. Forty-one retroperitoneal (R)/non-retroperitoneal (NR) well-differentiated-dedifferentiated (WD-DD) and 33 myxoid/round cell liposarcomas were reanalysed by immunocytochemical, molecular (nine cases) and fluorescence in situ hybridization (FISH) (one case) techniques. The results showed that all but one R WD-E cases carried the mdm2+, p53+, cdk4+ immunophenotype. In NR-WD liposarcomas, this immunophenotype was shared in five cases and the remainder showed mdm2+, p53-, cdk4+ in four and mdm2-, p53-, cdk4+ in one case, showing ring chromosomes by FISH analysis. TP53 mutations are confirmed to be closely correlated with NR-DD liposarcomas and no CDK4 involvement was found in the myxoid/round cell liposarcoma group. As well as confirming the synergistic effect of MDM2 and CDK4, these results are consistent with the concept that amplicon(s) excluding MDM2 may contribute to transformation and support a role of CDK4 in opposing p53 function, particularly in NR WD liposarcoma.

Blotting, Southern↗

PubMed2004

Evaluation of MDM2 and CDK4 amplification by real-time PCR on paraffin wax-embedded material: a potential tool for the diagnosis of atypical lipomatous tumours/well-differentiated liposarcomas.

Atypical lipomatous tumours/well-differentiated liposarcomas and dedifferentiated liposarcomas are characterized by 12q13-15 region amplification. In contrast, this molecular event has not been reported in benign lipomas. Within the 12q13-15 chromosomal region, the MDM2, SAS, HMGA2, and CDK4 genes are the most frequent targets of amplification. A series of lipomas (36 cases) and liposarcomas (48 cases) was analysed for MDM2 and CDK4 gene amplification by real-time PCR. MDM2 and CDK4 gene amplification was detected in 2.8% and 5.6% of lipomas and 98.2% and 82.4% of liposarcomas, respectively. Moreover, co-amplification of the two genes as well as a higher-level amplification was observed more frequently in dedifferentiated liposarcomas than in atypical lipomatous tumours/well-differentiated liposarcomas. Real-time PCR proved to be a fast and reliable method to characterize lipomas and liposarcomas by quantification of MDM2 and CDK4 gene amplification. It is applicable to paraffin wax-embedded tissues and could be useful when histological diagnosis is difficult.

Abdominal Neoplasms↗

PubMed2004

Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity.

Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas.

Adult↗