Limits...
Solitary fibrous tumor - clinicopathologic, immunohistochemical and molecular analysis of 28 cases.

Vogels RJ, Vlenterie M, Versleijen-Jonkers YM, Ruijter E, Bekers EM, Verdijk MA, Link MM, Bonenkamp JJ, van der Graaf WT, Slootweg PJ, Suurmeijer AJ, Groenen PJ, Flucke U - Diagn Pathol (2014)

Bottom Line: All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.STAT6 immunohistochemistry is another useful tool in diagnosing SFT.EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. rob.vogels@radboudumc.nl.

ABSTRACT

Background: Solitary fibrous tumor is a mesenchymal tumor of fibroblastic type, which can affect any region of the body. Recently, a recurrent gene fusion NAB2-STAT6 has been identified as molecular hallmark. The NAB2-STAT6 fusion leads to EGR1 activation and transcriptional deregulation of EGR1-dependent target genes and is a driving event in initiation of SFT. In this study, we report the clinicopathologic and RT-PCR findings and evaluated expression of STAT6 and EGR1 protein in a cohort of 28 SFTs.

Methods: 28 patients with a median age of 54 years were included with SFTs originating at different sites, most occurring in the lung and pleura (9, 32%), 5 in soft tissues of the lower extremities (18%) and 5 in the head and neck (18%). For detection of the NAB2-STAT6 fusion gene, RT-PCR was performed using RNA extracted from formalin-fixed and paraffin-embedded tissues. Immunohistochemistry was performed on all cases with antibodies against STAT6 and EGR1.

Results: All patients were treated by surgery, 3 with adjuvant chemo- or radiotherapy. Follow-up data of 18 patients could be obtained of which 2 patients died of metastatic disease 13 months and 52 years after first diagnosis. Sixteen patients have no evidence of disease with a median follow up of 29.5 months (range 7 - 120 months). NAB2-STAT6 fusion transcripts were found in 19/28 cases (68%). The most common fusion was between NAB2 exon 4 and STAT6 exon 3 (11/19, 58%), mainly occurring in pleuropulmonary lesions. All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.

Conclusions: The identification of the NAB2-STAT6 fusion in SFTs can provide important diagnostic information, especially in cases with aberrant morphology or when biopsy material is limited. STAT6 immunohistochemistry is another useful tool in diagnosing SFT. EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_224.

Show MeSH

Related in: MedlinePlus

Low level variable expression of EGR1 was seen in all samples (20x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4264260&req=5

Fig3: Low level variable expression of EGR1 was seen in all samples (20x).

Mentions: Immunohistochemical staining results are summarized in Table 3 and Table 4. All 28 cases were stained for STAT6 and all of them showed diffuse and strong nuclear positivity (Figure 2; 28/28, 100%). All 28 cases were stained for EGR1 (Figure 3). Most cases showed less than 25% nuclear positivity (12/28 cases score 1, 6/28 cases score 2). Few cases had more than 25% of all nuclei stained (5/28 cases score 3, 1/28 cases score 4, 3/28 cases score 5). Scoring of one case was not possible due to limited available tissue. All dedifferentiated liposarcomas (0/5 pos), deep benign fibrous histiocytomas (0/5 pos), sarcomatoid mesotheliomas (0/5 pos), low grade fibromyxoid sarcomas (0/7 pos), schwannomas (0/5 pos), malignant peripheral nerve sheath tumors (0/4 pos), gasto-intestinal stroma cell tumors (0/5 pos), synovial sarcomas (0/5 pos) and leiomyomas (0/6 pos) showed no nuclear staining for STAT6. EGR1 showed variable expression in the different tumor samples, as depicted in Table 4.Table 4


Solitary fibrous tumor - clinicopathologic, immunohistochemical and molecular analysis of 28 cases.

Vogels RJ, Vlenterie M, Versleijen-Jonkers YM, Ruijter E, Bekers EM, Verdijk MA, Link MM, Bonenkamp JJ, van der Graaf WT, Slootweg PJ, Suurmeijer AJ, Groenen PJ, Flucke U - Diagn Pathol (2014)

Low level variable expression of EGR1 was seen in all samples (20x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4264260&req=5

Fig3: Low level variable expression of EGR1 was seen in all samples (20x).
Mentions: Immunohistochemical staining results are summarized in Table 3 and Table 4. All 28 cases were stained for STAT6 and all of them showed diffuse and strong nuclear positivity (Figure 2; 28/28, 100%). All 28 cases were stained for EGR1 (Figure 3). Most cases showed less than 25% nuclear positivity (12/28 cases score 1, 6/28 cases score 2). Few cases had more than 25% of all nuclei stained (5/28 cases score 3, 1/28 cases score 4, 3/28 cases score 5). Scoring of one case was not possible due to limited available tissue. All dedifferentiated liposarcomas (0/5 pos), deep benign fibrous histiocytomas (0/5 pos), sarcomatoid mesotheliomas (0/5 pos), low grade fibromyxoid sarcomas (0/7 pos), schwannomas (0/5 pos), malignant peripheral nerve sheath tumors (0/4 pos), gasto-intestinal stroma cell tumors (0/5 pos), synovial sarcomas (0/5 pos) and leiomyomas (0/6 pos) showed no nuclear staining for STAT6. EGR1 showed variable expression in the different tumor samples, as depicted in Table 4.Table 4

Bottom Line: All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.STAT6 immunohistochemistry is another useful tool in diagnosing SFT.EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. rob.vogels@radboudumc.nl.

ABSTRACT

Background: Solitary fibrous tumor is a mesenchymal tumor of fibroblastic type, which can affect any region of the body. Recently, a recurrent gene fusion NAB2-STAT6 has been identified as molecular hallmark. The NAB2-STAT6 fusion leads to EGR1 activation and transcriptional deregulation of EGR1-dependent target genes and is a driving event in initiation of SFT. In this study, we report the clinicopathologic and RT-PCR findings and evaluated expression of STAT6 and EGR1 protein in a cohort of 28 SFTs.

Methods: 28 patients with a median age of 54 years were included with SFTs originating at different sites, most occurring in the lung and pleura (9, 32%), 5 in soft tissues of the lower extremities (18%) and 5 in the head and neck (18%). For detection of the NAB2-STAT6 fusion gene, RT-PCR was performed using RNA extracted from formalin-fixed and paraffin-embedded tissues. Immunohistochemistry was performed on all cases with antibodies against STAT6 and EGR1.

Results: All patients were treated by surgery, 3 with adjuvant chemo- or radiotherapy. Follow-up data of 18 patients could be obtained of which 2 patients died of metastatic disease 13 months and 52 years after first diagnosis. Sixteen patients have no evidence of disease with a median follow up of 29.5 months (range 7 - 120 months). NAB2-STAT6 fusion transcripts were found in 19/28 cases (68%). The most common fusion was between NAB2 exon 4 and STAT6 exon 3 (11/19, 58%), mainly occurring in pleuropulmonary lesions. All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.

Conclusions: The identification of the NAB2-STAT6 fusion in SFTs can provide important diagnostic information, especially in cases with aberrant morphology or when biopsy material is limited. STAT6 immunohistochemistry is another useful tool in diagnosing SFT. EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_224.

Show MeSH
Related in: MedlinePlus