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Cyril Fisher

Publications and source records attributed to Cyril Fisher.

At least 19 recordsLinked to original sources
PubMed2006

Epithelioid sarcoma of Enzinger.

Epithelioid sarcoma was named in 1970 in a classic paper by Enzinger, who expanded the observations in a larger series in 1985. He defined a sarcoma with a peak incidence in young adult males and a predilection for extremities, involving subcutis or deeper tissue and extending along tendon sheaths or aponeuroses. The tumor forms nodules with central necrosis surrounded by bland polygonal cells with eosinophilic cytoplasm and peripheral spindling. Fibromalike, angiomatoid, and proximal aggressive variants (with larger cells, prominent nuceloi, and rhabdoid change) have since been described. Epithelioid sarcomas regularly express vimentin, cytokeratins, and epithelial membrane antigen, and about half are positive for CD34, but a wide range of other antigens can be expressed. S100 protein, desmin, and FLI-1 are usually negative. The ultrastructure displays epithelial and mesenchymal features including myofibroblastic differentiation. There are no specific genetic findings but several cases display chromosomal abnormalities in the 22q region. The tumor has no normal cellular counterpart and differs from both synovial sarcoma and carcinoma. There is a wide differential diagnosis from numerous benign and malignant conditions, including granuloma annulare, melanoma, and epithelioid vascular neoplasms. Epithelioid sarcoma has a high recurrence rate, which can be reduced by adequate surgery, and up to 40% metastasize, to regional lymph nodes, to lung, and other locations including scalp. Adverse prognostic factors include large size, male sex, older age, necrosis, vascular invasion, rhabdoid cytomorphology, and inadequate excision. Thirty-six years after Enzinger's original account, epithelioid sarcoma remains a clinically and pathologically distinct, indolent but aggressive sarcoma of indeterminate lineage.

Biomarkers, Tumor↗
PubMed2006

The immunohistochemical profile of malignant mesotheliomas of the tunica vaginalis: a study of 20 cases.

Malignant mesotheliomas of the testis arise from the tunica vaginalis, formed from the evagination of the abdominal peritoneum into the scrotum. The immunohistochemical profile of the tunica vaginalis and associated neoplasms is often extrapolated from thoracic studies. Testicular series are uncommon, usually derived from previous case studies and literature reviews. The immunohistochemical findings in 20 cases originally diagnosed as malignant mesotheliomas are presented. Archival testicular malignant mesothelioma specimens from 1959 to 2004 were collected from hospitals throughout the United Kingdom and from the authors' own archives. Hematoxylin and eosin-stained sections were reviewed, and selected sections from each case were then examined using an immunohistochemical panel of eight antibodies: calretinin (Zymed, 1:200), epithelial membrane antigen (EMA) (DAKO, 1:50), thrombomodulin (DAKO 1:5), CK7 (DAKO, 1:100), CK5-CK6 (DAKO, 1:10), BerEp4 (DAKO, 1:25), carcinoembryonic antigen (CEA) (DAKO, 1:10), and CK20 (DAKO, 1:100). The EnVision technique was used for all antibodies. Sections were reviewed independently by three pathologists. Electron microscopy was performed on selected cases. In all cases, the morphologic light microscopy criteria for a diagnosis of malignant mesothelioma were present. However, two tumors were later excluded from the study because of diffuse strong positive immunostaining with CK20 and BerEp4 and an ultrastructural appearance of adenocarcinoma. Of the remaining cases, 15 of 18 (83%) were purely epithelioid in type, showing a mixture of papillary, tubular, and solid patterns, and 3 of 18 (17%) showed a mixed sarcomatoid/epithelioid pattern. All cases were positive for calretinin and EMA (100%), 16 of 18 (89%) were positive for thrombomodulin, and 15 of 18 (83%) were positive for CK7. CK5-CK6 positivity was present in 13 of 18 (72%) but varied in strength and distribution; 2 of 18 (11%) were positive for BerEp4. All the cases were negative for CK20 and CEA. Four of the 18 cases were examined by electron microscopy, which revealed long thin microvilli supporting a diagnosis of malignant mesothelioma. This study has shown that the immunocytochemical profile of testicular malignant mesotheliomas is similar to those arising in the pleura, with diffuse positivity for calretinin, EMA, thrombomodulin, and CK7, and negative for CK20 and CEA. Focal weak positivity may be encountered with BerEp4. However, histopathologists should be aware of the variability in CK5-6 staining in testicular specimens when compared with pleural mesotheliomas.

Aged↗
PubMed2006

Aggressive fibromatosis: MRI features with pathologic correlation.

OBJECTIVE: We present the MRI features with pathologic correlation of aggressive fibromatosis, incorporating 203 cases over a 5-year period from the Royal Marsden Hospital Sarcoma Unit database. MATERIALS AND METHODS: Sixty patients had imaging available for retrospective review of which 29 had preoperative MRI and final histopathologic diagnosis of aggressive fibromatosis. RESULTS: The average age at diagnosis was 41.3 years with a female-to-male sex ratio of 1.2:1. Twenty lesions were extraabdominal; six, intraabdominal; and three, in the abdominal wall (classic desmoid). The average tumor size was 6.4 cm (range, 2.2-13.7 cm). Intraabdominal aggressive fibromatosis produced the largest tumors, averaging 9.5 cm. Most lesions were ovoid (52%) or infiltrative (34.5%) in outline with an irregular or lobulated contour (76%). The lesions crossed major fascial boundaries in 31% of cases overall and in 66% of patients referred for recurrent disease. On MRI, homogeneous isointensity or mild hyperintensity on T1-weighted images and heterogenous high signal on T2-weighted or STIR images were seen. All lesions enhanced after IV gadolinium, usually avidly. In contrast to previous reports, 38% of cases failed to show low signal on all pulse sequences and no abnormalities were seen in local bone structures. Histology showed sheets of bland spindle cells in dense collagen and did not vary with the MRI signal characteristics of the lesion. Patients referred for recurrent disease were most likely to have a recurrence after surgery. MRI and pathology findings did not predict recurrence. CONCLUSION: Accurate diagnosis and staging of aggressive fibromatosis by MRI have important treatment and prognostic implications.

Adolescent↗
PubMed2005

Differential sensitivity of liposarcoma subtypes to chemotherapy.

Liposarcoma is one of the most common soft tissue sarcomas and has a number of different subtypes: well-differentiated; dedifferentiated; myxoid/round cell; and pleomorphic. However, the response of these subgroups to chemotherapy is not well documented. In this study, we have conducted a retrospective analysis of a prospectively maintained database of soft tissue sarcoma patients treated at the Royal Marsden Hospital. Eighty-eight liposarcoma patients who received chemotherapy between August 1989 and June 2004 were identified. The response rates to chemotherapy of the different histological subtypes and overall and progression free survival were investigated. Survival according to histological grade was also assessed. A statistically significant higher response rate to first-line chemotherapy was observed in patients with myxoid liposarcoma compared to de- and well-differentiated tumours, 48% (95%CI; 28-69) and 11% (95%CI; 2-29), P = 0.005. Similarly, those with myxoid liposarcoma had a significantly higher response rate compared to all other liposarcoma patients, 48% (95%CI; 28-69) and 18% (95%CI; 8-31). Patients with lower grade tumours had better overall survival. This retrospective analysis suggests that myxoid liposarcoma is relatively chemosensitive in comparison to a combination of other liposarcomas, and in particular de- and well-differentiated tumours. Further confirmation of these results should be sought by similar analyses of other databases.

Adult↗
PubMed2005

Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults.

We have previously identified amplification at 4q12 in testicular germ cell tumors of adolescents and adults centered around the KIT gene encoding a tyrosine kinase transmembrane receptor. Analysis of primary testicular germ cell tumors totaling 190 cases revealed 21% of the seminoma subtype with an increased copy number of KIT whereas this change was rarely found in the nonseminomas. In most cases, gain of KIT did not include the immediately flanking noncoding DNA or the flanking genes KDR and PDGFRA. Increased copy number of KIT was not found in the putative precursor lesion, carcinoma in situ (CIS), adjacent to tumor with this change. KIT overexpression was found independent of gain and KIT immunostaining was stronger in selected cases with gain of KIT compared to those without. Taken together with activating mutations of KIT in exon 17 identified in 13% of seminomas, this suggests that the KIT gene product plays a role in the progression of CIS towards seminoma, the further understanding of which may lead to novel less toxic therapeutic approaches.

Adolescent↗
PubMed2005

No evidence for epigenetic inactivation of fumarate hydratase in leiomyomas and leiomyosarcomas.

Germline mutations in Fumarate Hydratase (FH) cause the development of leiomyomas and leiomyosarcomas in the syndromes Multiple Cutaneous and Uterine Leiomyomata (MCUL1) and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). There is little evidence, however, that FH mutation plays a role in the development of sporadic leiomyomas or leiomyosarcomas. Such observations do not, however, exclude a role for FH in tumour development outside the context of MCUL1/HLRCC, as it is possible that FH expression could be silenced by epigenetic mechanisms. To explore this possibility we have developed a highly specific antibody to FH and analysed a series of forty-five fresh-frozen uterine leiomyomas and nine leiomyosarcomas for FH expression.

Adult↗
PubMed2005

Inflammatory myofibroblastic tumour of the gallbladder.

BACKGROUND: Inflammatory myofibroblastic tumour (IMT) is a benign, nonmetastasizing proliferation of myofibroblasts with a potential for local infiltration, recurrence and persistent local growth. CASE REPORT: We report a case of a 51 year-old female, who had excision of a gallbladder tumour. Histopathology showed it to be IMT of the gallbladder. CONCLUSION: The approach to these tumours should be primarily surgical resection to obtain a definitive diagnosis and relieve symptoms. IMT has a potential for local infiltration, recurrence and persistent local growth.

Journal Article↗
PubMed2005

Relationship between MYCN copy number and expression in rhabdomyosarcomas and correlation with adverse prognosis in the alveolar subtype.

PURPOSE: Amplification of the transcription factor MYCN is an important molecular diagnostic tool in stratifying treatment for neuroblastoma. Increased copy number and overexpression of MYCN in the pediatric cancer rhabdomyosarcoma has been described in a number of small studies with conflicting conclusions about its association with clinicopathologic characteristics. We aimed to study the phenomenon in the largest series to date. PATIENTS AND METHODS: Using quantitative polymerase chain reaction, we measured MYCN copy number and expression levels in rhabdomyosarcoma samples from 113 and 92 individuals with a confirmed diagnosis of rhabdomyosarcoma, respectively. RESULTS: Increased copy number of MYCN was found to be a feature of both the embryonal and alveolar subtypes. The copy number and expression levels were significantly greater in the alveolar subtype, although the range of expression in both subtypes spanned several orders of magnitude. MYCN copy number showed a significant correlation with expression in the alveolar subtype; this relationship between copy number and expression could be modeled as a logarithmic function. It is notable that relatively high expression frequently occurred in embryonal rhabdomyosarcoma without high copy number and that low expression was found in some cases with high copy number. In patients with alveolar rhabdomyosarcoma, overexpression (greater than median) or gain of genomic copies of MYCN were significantly associated with adverse outcome. CONCLUSION: MYCN deregulation is a feature of rhabdomyosarcoma tumorigenesis, defines groups of patients with a poor prognosis, and is a potential target for novel therapies.

Child↗
PubMed2005

Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene.

Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either more benign or more malignant tumor types. Cytogenetic analyses have identified a recurrent balanced translocation t(7;16) (q32-34;p11), later shown by molecular genetic approaches to result in a FUS/CREB3L2 fusion gene. Whereas preliminary studies suggest that this gene rearrangement is specific for LGFMS, its incidence in this tumor type and the possible existence of variant fusion genes have not yet been addressed. For this purpose, a series of potential LGFMS were obtained from nine different soft-tissue tumor centres and subjected to molecular analysis as well as careful histopathologic review. Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive. In one of the tumors with typical LGFMS appearance, we found that FUS was fused to the CREB3L1 gene instead of CREB3L2. The proteins encoded by these genes both belong to the same basic leucine-zipper family of transcription factors, and display extensive sequence homology in their DNA-binding domains. Thus, it is expected that the novel FUS/CREB3L1 chimera will have a similar impact at the cellular level as the much more common FUS/CREB3L2 fusion protein. Taken together, the results indicate that virtually all LGFMS are characterized by a chimeric FUS/CREB3L2 gene, and that rare cases may display a variant FUS/CREB3L1 fusion.

Adolescent↗
PubMed2005

PDGF-A, PDGF-Rbeta, TGFbeta3 and bone morphogenic protein-4 in desmoplastic small round cell tumors with EWS-WT1 gene fusion product and their role in stromal desmoplasia: an immunohistochemical study.

Histologically, desmoplastic small round cell tumor is composed of the characteristic neoplastic small round cells with divergent differentiation, and distinct desmoplastic stroma. Genetically, the tumor shows a characteristic 11;22 translocation, involving the EWS gene on chromosome 22 and the WT1gene on chromosome 11 to produce an EWS-WT1 fusion gene which generates a chimeric protein functioning as a novel transcription factor that activates expression of target genes such as PDGF-A. Expression of PDGF-A, a potent growth factor for fibroblasts, has been detected in desmoplastic small round cell tumors and has been linked to the characteristic desmoplasia in these tumors. Bone morphogenic proteins, which are members of the TGFbeta superfamily play a complex role in regulating cell growth and differentiation and bone formation but have not been evaluated in desmoplastic small round cell tumors. In all, 24 desmoplastic small round cell tumors with EWS-WT1 fusion product confirmed by RT-PCR analysis were evaluated for expression of PDGF-A, PDGF-Rbeta, TGFbeta3 and bone morphogenic protein-4 by standard immunohistochemical methods with antigen retrieval on paraffin sections. Immunoreactivity was evaluated semiquantitively. Tumor-associated desmoplasia was quantified using a three-tier scale on hematoxylin- and eosin-stained sections. Desmoplastic small round cell tumors showed variable immunoreactivity with TGFbeta3 (21/24), BMP4 (14/21), PDGF-A (19/24) and PDGF-Rbeta (16/22). Less frequently, the stromal cells showed reactivity with TGFbeta3, PDGF-Rbeta and PDGF-A. Tumor-associated desmoplasia was prominent in eight, intermediate in seven and weak in nine cases. There was no correlation between tumor-associated desmoplasia and the markers tested except PDGF-A. In contrast to a previous study, our study showed that the level of PDGF-A expression inversely correlated with tumor-associated desmoplasia. Other targets of the EWS-WT1 transcription factor other than PDGF-A may be directly responsible for the prominent tumor-associated desmoplasia seen in desmoplastic small round cell tumor.

Abdominal Neoplasms↗
PubMed2005

Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma.

Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Molecular genetic data of well-characterized cases of epithelioid sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by conventional metaphase comparative genomic hybridization reported recurrent gains at chromosome 11q13, a region containing many genes, including the cyclin D1 gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The objective of this study was to examine cyclin D1 expression in epithelioid sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by immunohistochemistry, were evaluated by fluorescence in situ hybridization (FISH) and RNA in situ hybridization (RISH) for amplification of the cyclin D1 gene and messenger RNA (mRNA) expression, respectively. Seven of eight cases showed a typical eusomic state. One case showed pseudoamplification due to aneusomy/polysomy. There was no evidence of cyclin D1 gene amplification or messenger RNA overexpression detected by FISH or RNA in situ hybridization analyses, respectively. Our data clearly demonstrate that cyclin D1 protein is upregulated in epithelioid sarcoma, suggesting a role for this cell cycle regulator in the pathogenesis of epithelioid sarcoma. The high level of cyclin D1 protein expression in epithelioid sarcoma appears to be regulated by translational and/or post-translational mechanisms.

Cyclin D1↗
PubMed2005

Nuclear beta-catenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions.

Deep fibromatoses (desmoid tumors) are clonal myofibroblastic proliferations that are prone to aggressive local recurrences but that do not metastasize. They must be distinguished from a host of fibroblastic and myofibroblastic lesions as well as from smooth muscle neoplasms. Virtually all deep fibromatoses have somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of beta-catenin. Since low-grade sarcomas in general lack beta-catenin and since reactive proliferations would not be expected to have it, we predicted that nuclear beta-catenin expression would be detected in deep fibromatoses but absent in other entities in the differential diagnosis. We evaluated the role of beta-catenin to help differentiate distinguish deep fibromatoses from congeners. Formalin-fixed, paraffin-embedded sections from 21 lesions from 20 patients with deep fibromatoses were stained with monoclonal beta-catenin antibody (Transduction Laboratories) and compared with low-grade fibromyxoid sarcoma (n=12), leiomyosarcoma (n=10), various other fibrosarcoma variants (n=13, including 3 myofibrosarcomas, 3 sclerosing epithelioid fibrosarcomas, 5 low-grade fibrosarcomas, 1 classic fibrosarcoma arising in dermatofibrosarcoma protuberans, 1 inflammatory myxohyaline tumor/myxoinflammatory fibroblastic sarcoma), myofibroma/myofibromatosis (n=12), nodular fasciitis (n=11), and scars (n=9). Nuclear and cytoplasmic staining was assessed. All 21 examples of deep fibromatosis displayed nuclear beta-catenin (focal nuclear staining in one case to 90% staining). All other lesions tested (n=67) lacked nuclear labeling for beta-catenin, showing only cytoplasmic accumulation. beta-Catenin immunohistochemistry separates deep fibromatosis from entities in the differential diagnosis, a finding that can be exploited for diagnosis. Most fibromatoses have diffuse nuclear staining although occasional examples only focally label.

Adolescent↗
PubMed2005

Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature.

PEComas, occasionally associated with the tuberous sclerosis complex, are defined by the presence of perivascular epithelioid cells that coexpress muscle and melanocytic markers. This family of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations. Because non-AML/non-LAM PEComas are extremely rare and their natural history and prognostic features undefined, we present our experience with 26 PEComas of soft tissue and the gynecologic tract, the largest series to date. We also performed a detailed review of the literature, with special attention to features predictive of clinical behavior. All PEComas exclusive of AML and LAM were retrieved from our consultation files. Immunohistochemistry for pan-cytokeratin (CK), S-100 protein, smooth muscle actins (SMA), desmin, vimentin, HMB45, Melan-A, microphthalmia transcription factor (MiTF), TFE3, CD117, and CD34 was performed. Clinical follow-up information was obtained. Fisher's exact test was performed. The median patient age was 46 years (range, 15-97 years); there was a marked female predominance (22 females, 4 males). Sites of involvement included the omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each). The tumors ranged from 1.6 to 29 cm in size (median, 7.8 cm). Tumors were epithelioid (N = 9), spindled (N = 7), or mixed (N = 10). Multinucleated giant cells were present in 18 cases. High nuclear grade was noted in 10 cases, high cellularity in 7 cases, necrosis in 8 cases, and vascular invasion in 3 cases. Mitotic activity was 0 to 50 mitotic figures (MF)/50 high power fields (HPF) (median, 0 MF/50 HPF) with atypical MF in 6 cases. IHC results were: SMA (20/25), desmin (8/22), HMB45 (22/24), Melan-A (13/18), MITF (9/18), S-100 protein (8/24), CK (3/23), vimentin (12/14), TFE3 (5/17), c-kit (1/20), and CD34 (0/7). Clinical follow-up (24 of 26 patients, 92%; median, 30 months; range, 10-84 months) showed 3 local recurrences and 5 distant metastases. At last available clinical follow-up, 2 patients (8%) were dead of disease, 4 patients (17%) were alive with metastatic or unresectable local disease, and 18 patients (75%) were alive with no evidence of disease. No patient in our series had a history of tuberous sclerosis complex. Recurrence and/or metastasis was strongly associated tumor size > median size (8 cm), mitotic activity greater than 1/50 HPF, and necrosis. We conclude that PEComas of soft tissue and gynecologic origin may be classified as "benign," "of uncertain malignant potential," or "malignant." Small PEComas without any worrisome histologic features are most likely benign. PEComas with nuclear pleomorphism alone ("symplastic") and large PEComas without other worrisome features have uncertain malignant potential. PEComas with two or more worrisome histologic features should be considered malignant. Occasional PEComas express unusual markers, such as S-100 protein, desmin, and rarely CK. The role of TFE3 in PEComas should be further studied.

Adolescent↗
PubMed2004

A gene expression signature associated with metastatic outcome in human leiomyosarcomas.

Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we have chosen leiomyosarcoma as a model for examining the relationship between gene expression profile and the development of metastasis in soft tissue sarcomas. Using cDNA microarray, we have identified a gene expression signature associated with metastasis in sarcoma that allowed prediction of the future development of metastases of primary tumors (Kaplan-Meier analysis P = 0.001). Our finding may aid the tailoring of therapy for individual sarcoma patients, where the aggressiveness of treatment is affected by the predicted outcome of disease.

Gene Expression Profiling↗
PubMed2004

Intra-abdominal metastases from soft tissue sarcoma.

OBJECTIVE: To define the clinical features and prognosis of patients with abdominal metastasis from primary soft tissue sarcoma (STS) at other sites. METHODS: All patients with abdominal metastasis from STS were identified from the Royal Marsden Hospital Sarcoma Unit prospective database from January 1990 to July 2001. RESULTS: Nineteen patients developed abdominal metastasis out of a cohort of 2127 patients (0.9%) evaluated during the study interval. The median age was 49 (19-71) years. The median time to abdominal metastasis from diagnosis of the primary was 27 (8-91) months. The presenting complaints were incomplete intestinal obstruction (n = 5), abdominal pain (n = 4), mass (n = 2), gastrointestinal bleed (n = 2), urinary obstruction (n = 2), anorexia (n = 1), and abdominal distension (n = 1). Emergency laparotomy was done for perforative peritonitis (n = 2), intussusception (n = 2), and bleed in spleen (n = 1). Two patients were asymptomatic. The common histologies were myxoid liposarcoma (n = 6) and leiomyosarcoma (n = 4). The median follow-up of survivors post metastasis was 12 months. Abdominal metastatectomy was performed in 16 patients, 3 of these patients had abdominal recurrences. The 1- and 2-year overall disease specific survival for the 19 patients was 66% (SE = 11%) and 43% (SE = 13%) with a median survival of 13 months (95% CI = 11.8-14.7). Metastasectomy was associated with slight improved median post-metastasis survival (33 months vs. 8 months for unresected patients). CONCLUSIONS: Although abdominal metastasis is rare, vigilance is warranted. Symptomatic patients should be examined and investigated thoroughly for metastases. Surgery is the treatment of choice for patients with an acute presentation; however, survival is dismal.

Abdominal Neoplasms↗
PubMed2004

Myofibrosarcoma.

Myofibrosarcomas are malignant tumours of myofibroblasts, which have been recognised for many years, but have become clearly defined only recently. They are low- or high-grade sarcomas that arise in soft tissue or bone in adults or children. Low-grade myofibrosarcomas are infiltrative tumours, usually in deep soft tissue, with a predilection for the head and neck region, which display a range of microscopic appearances from fasciitis-like to fibrosarcoma-like; all cases at least focally display nuclear pleomorphism. They express smooth-muscle actin and calponin, and some express desmin, but most lack h-caldesmon. Low-grade myofibrosarcomas can recur but rarely metastasise. Their differential diagnosis is from benign myofibroblastic proliferations, such as fasciitis and fibromatosis, as well as from fibrosarcoma and leiomyosarcoma. Pleomorphic myofibrosarcomas are high-grade pleomorphic sarcomas (malignant fibrous histiocytoma), which show ultrastructural evidence of myofibroblastic differentiation. They closely resemble malignant fibrous histiocytoma clinically and morphologically, but are more frequently actin positive. This article describes the low- and high-grade variants of myofibrosarcoma and other malignant tumours with myofibroblastic differentiation.

Adult↗
PubMed2004

Amplification and overexpression of E2F3 in human bladder cancer.

We demonstrate that, in human bladder cancer, amplification of the E2F3 gene, located at 6p22, is associated with overexpression of its encoded mRNA transcripts and high levels of expression of E2F3 protein. Immunohistochemical analyses of E2F3 protein levels have established that around one-third (33/101) of primary transitional cell carcinomas of the bladder overexpress nuclear E2F3 protein, with the proportion of tumours containing overexpressed nuclear E2F3 increasing with tumour stage and grade. When considered together with the established role of E2F3 in cell cycle progression, these results suggest that the E2F3 gene represents a candidate bladder cancer oncogene that is activated by DNA amplification and overexpression.

Base Sequence↗