Heterogeneous genetic profiles in soft tissue myoepitheliomas

Hallor, Karolin H.; Teixeira, Manuel R.; Fletcher, Christopher D.�M.; Bizarro, Susana; Staaf, Johan; Domanski, Henryk A.; Steyern, Fredrik Vult von; Panagopoulos, Ioannis; Mandahl, Nils; Mertens, Fredrik

doi:10.1038/modpathol.2008.124

Cited by 46 publications

(52 citation statements)

References 25 publications

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“…[28][29][30] Although some soft tissue myoepitheliomas may demonstrate PLAG1 rearrangement, 31 many soft tissue myoepitheliomas and mixed tumors of the skin have an EWSR1 gene rearrangement, which is not present in mixed tumors of salivary glands. 12,27,[32][33][34] Myoepithelioma of bone is rare; 9 cases have been reported in the literature (Table 3). 16,18,20,27 Combining our cases with those previously described, men and women are affected at a ratio 5:4, and the age range is 14 to 55 (mean, 32) years.…”

Section: Discussionmentioning

confidence: 95%

Primary Myoepithelioma of Bone

Kurzawa

Kattapuram²,

Hornicek³

et al. 2013

American Journal of Surgical Pathology

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The clinical and pathologic features of 8 primary myoepitheliomas of bone were analyzed. There were 5 female and 3 male patients who ranged in age from 16 to 49 (mean, 33.5) years. Three tumors arose in the ilium, 2 in the tibia, and 1 each in the maxilla, sacrum, and L1 vertebral body. Microscopically, the tumors had a solid, lobulated, reticular, or storiform growth pattern and were predominantly composed of spindle-shaped cells arranged in intersecting fascicles with eosinophilic cytoplasm. The round to polygonal epithelioid cells were arranged randomly or formed small clusters and contained variable amounts of eosinophilic or clear cytoplasm. Immunohistochemically, all the tumors were positive for vimentin and S100 protein, and 7 were positive for epithelial membrane antigen. No tumors were positive for keratin (AE1.3/CAM5.2). Smooth muscle actin was positive in 3 tumors and negative in 4, whereas desmin was negative in all 7 tumors tested. Nuclear staining for p63 was negative in 3 tested tumors. Staining for GFAP and CD34 was performed on 4 and 5 tumors, respectively, and all showed no expression. Fluorescence in situ hybridization for EWSR1 rearrangement was performed in 7 tumors. Five tumors (71%) showed the presence of EWSR1 gene rearrangement, and 2 were negative. Cytogenetic studies conducted on 1 tumor showed 46,XY,t(1;22)(q21;q12) associated with EWSR1-PBX1 fusion. Surgical procedures included curettage in 3 patients, resection in 3 patients, and 2 patients only had an open biopsy. Follow-up information was available for 4 patients; all remain free of disease with no recurrence. Although experience with primary myoepithelioma of bone is limited, histologically, banal tumors appear to behave in a benign manner, and conservative surgery appears to be sufficient treatment. Immunohistochemical and molecular analyses are helpful in their accurate identification.

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Section: Discussionmentioning

confidence: 95%

Primary Myoepithelioma of Bone

Kurzawa

Kattapuram²,

Hornicek³

et al. 2013

American Journal of Surgical Pathology

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“…Elevated activity of PLAG1 primarily results from recurrent translocations that lead to upregulation of the PLAG1 gene (Kas et al, 1997, 1998; Voz et al, 1998, 2000b; Astrom et al, 1999). Contrary to the extensive cytogenetic and molecular genetic studies of pleomorphic adenomas over the course of the past 2.5 decades (Mark and Dahlenfors, 1986; Bullerdiek et al, 1993; Kas et al, 1997, 1998; Voz et al, 1998, 2000a, 2000b, 2004; Astrom et al, 1999; Asp et al, 2006; Van et al, 2007), few studies have focused on exploring the genetics of myoepithelial tumors in soft tissues (Hallor et al, 2008; Antonescu et al, 2010). This is partly because of the novelty of the myoepithelioma concept in soft tissue (where there is no evident normal cellular counterpart), and partly due to the rarity of these tumors at extra-salivary sites and the difficulty in classifying them.…”

Section: Introductionmentioning

confidence: 99%

A subset of cutaneous and soft tissue mixed tumors are genetically linked to their salivary gland counterpart

Bahrami

Dalton

Krane

et al. 2011

Genes Chromosomes & Cancer

103

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Neoplasms morphologically similar to mixed tumors and myoepitheliomas of the salivary glands, under the broad concept of myoepithelial neoplasia, have recently been defined in the skin and soft tissue; however, to date, no data have supported a shared genetic background with their salivary gland counterpart. From a large body of research, it has been well established that rearrangement of pleomorphic adenoma gene 1 (PLAG1) leads to aberrant expression of its protein and is pathogenically relevant in the development of salivary mixed tumors. On the other hand, in soft tissue lesions, compelling evidence suggests that EWSR1 is involved in a significant subset. To examine the hypothesis that there is a genetic link between these histologically similar tumors at different sites, we randomly selected 20 benign myoepitheliomas/mixed tumors of skin and soft tissue (10 cases each). Nineteen cases could be immunostained for PLAG1, of which 11 cases showed distinct nuclear staining with moderate or strong intensity in a significant number of cells. Interphase fluorescence in situ hybridization (FISH) for PLAG1 was successfully performed in 11 cases (7 in skin, 4 in soft tissue) and was positive for gene rearrangement in 8 cases (5 in skin, 3 in soft tissue). All PLAG1-rearranged tumors, except one, had clear-cut ductal structures and were immunoreactive for PLAG1. In our series, tumors with PLAG1 alteration shared a common morphologic phenotype characterized by prominent tubuloductal differentiation, suggesting that myoepithelial neoplasms with genuine salivary gland-like morphology, so-called soft tissue/cutaneous mixed tumors, are genetically related to their salivary gland counterpart.

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“…Conversely, a different study showed that cutaneous mixed tumors could also harbor EWSR1 abnormalities (Flucke et al, 2011). No HMGA2 gene abnormalities were discovered so far in soft tissue or bone ME tumors (Hallor et al, 2008; Antonescu et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Novel FUS‐KLF17 and EWSR1‐KLF17 fusions in myoepithelial tumors

Huang

Chen

Zhang

et al. 2015

Genes Chromosomes & Cancer

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Myoepithelial (ME) tumors of soft tissue and bone display a heterogeneous histologic spectrum and in about half of the cases harbor EWSR1 gene rearrangements. Despite rare case reports, the prevalence of FUS gene abnormalities and its related fusion partners remains undetermined among ME tumors. Therefore, we screened 66 EWSR1-negative ME tumors for FUS abnormalities by fluorescence in situ hybridization (FISH). In an index FUS-rearranged case, 3'-Rapid Amplification of cDNA Ends (RACE) was applied to identify the fusion partner. Results were further confirmed by RT-PCR, followed by FISH screening the entire cohort of FUS-rearranged and EWSR1-positive ME lesions lacking a known fusion partner. The correlation between genotype and clinicopathological features was also investigated. As a result, six (9%) FUS-rearranged cases were identified, spanning divergent age groups, tumor locations, and morphologic features. A novel FUS-KLF17 fusion was identified by 3’RACE in an 11 year-old girl with a foot lesion associated with locoregional metastases. Three additional cases with FUS-KLF17 fusions were identified and one KLF17 rearrangement (6.3%) was found among the 16 EWSR1-positive cases tested. The KLF17-related ME tumors affected younger patients and often exhibited trabecular growth in a myxohyaline stroma, but this genotype did not correlate with a malignant phenotype. In conclusion, a small subset of ME tumors harbor FUS rearrangements, two thirds of them being associated with KLF17 fusion. FUS FISH analysis is recommended in EWSR1-negative lesions in which a ME diagnosis is suspected. KLF17 is also a rare gene fusion partner to EWSR1-rearranged ME tumors.

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Heterogeneous genetic profiles in soft tissue myoepitheliomas

Cited by 46 publications

References 25 publications

Primary Myoepithelioma of Bone

Primary Myoepithelioma of Bone

A subset of cutaneous and soft tissue mixed tumors are genetically linked to their salivary gland counterpart

Novel FUS‐KLF17 and EWSR1‐KLF17 fusions in myoepithelial tumors

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