Nestin expression as a new marker in malignant peripheral nerve sheath tumors

Shimada, Satoko; Tsuzuki, Toyonori; Kuroda, Makoto; Nagasaka, Tetsuro; Hara, Kazuo; Takahashi, Emiko; Hayakawa, Soichiro; Ono, Kenzo; Maeda, Nobutaka; Mori, Naoyoshi; Illei, Peter B.

doi:10.1111/j.1440-1827.2006.02059.x

Cited by 47 publications

(54 citation statements)

References 25 publications

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“…Most immunohistochemical markers associated with malignant peripheral nerve sheath tumors, such as bcl2, CD56, nestin and S100 protein, are also expressed in a significant proportion of synovial sarcoma. 10,12,[29][30][31] TLE1 shows promise as a marker of synovial sarcoma, but weak and variable expression can be seen in malignant peripheral nerve sheath tumors. [32][33][34][35] Consequently, genetic and molecular tests to demonstrate t(X;18) rearrangement or SS18-SSX fusion, respectively, have become routine at many specialized centers to confirm the diagnosis of synovial sarcoma.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma

et al. 2014

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Synovial sarcoma and malignant peripheral nerve sheath tumor pose a significant diagnostic challenge given similar histomorphology. The distinction is further complicated by similar immunophenotype and especially by occasional synovial sarcomas that present as intraneural tumors. Although the presence of a t(X;18) rearrangement or expression of TLE1 can help confirm the diagnosis of synovial sarcoma, negative results for these tests are not diagnostic of malignant peripheral nerve sheath tumor. The SOX10 transcription factor, a putative marker of neural crest differentiation, may have diagnostic utility in this differential, but immunohistochemical data are limited. The goal of the present study was to determine the diagnostic utility of SOX10 to discriminate between synovial sarcoma and malignant peripheral nerve sheath tumor. Forty-eight cases of malignant peripheral nerve sheath tumor, all from patients with documented neurofibromatosis, and 97 cases of genetically confirmed synovial sarcoma, including 4 intraneural synovial sarcomas, were immunohistochemically stained for SOX10. The stain was scored for intensity and fraction of cells staining. Thirty-two of 48 malignant peripheral nerve sheath tumors (67%) were SOX10-positive. The majority of malignant peripheral nerve sheath tumors showed Z2 þ staining, but staining did not correlate with grade. By contrast, only 7/97 (7%) synovial sarcomas were SOX10-positive. Only three synovial sarcomas showed Z2 þ staining but, importantly, two of these were intraneural synovial sarcoma. Therefore, SOX10 is a specific (93%), albeit not very sensitive (67%), diagnostic marker to support a diagnosis of malignant peripheral nerve sheath tumor over synovial sarcoma. Furthermore, the stain needs to be interpreted with caution in intraneural tumors in order to avoid a potential diagnostic pitfall. It remains to be determined whether SOX10-positive cells in intraneural synovial sarcoma represent entrapped Schwann cells, synovial sarcoma cells or both.

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Section: Discussionmentioning

confidence: 99%

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma

et al. 2014

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“…41 Our finding here is similar to previous reports, in which higher mitotic rate was observed in mixed versus pure desmoplastic tumors, and correlated with more aggressive biological behavior. 4,24 Nestin is an intermediate filament protein and marker for melanoma-initiating cells; immunohistochemical expression has been identified in desmoplastic melanoma 42 and is associated with poor prognosis in conventional melanomas. 13 CD271 (p75NTR) is a neural crest stem cell marker expressed in melanoma cells, which is associated with higher metastatic potential and worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

et al. 2012

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Desmoplastic melanoma is subclassified into pure and mixed variants with a higher rate of lymph node metastasis in the latter. Given that reasons for these biological differences are not currently known, we investigated these subtypes with techniques that included genetic and immunohistochemical analyses of 43 cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13 and 17). Immunohistochemical stains were performed with antibodies to markers of significance with respect to biological potential of nevomelanocytic proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin, SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no mutations were found in any of the cases on analyses of exons 11, 13 and 17 of the c-KIT gene (P ¼ NS for all). For immunohistochemical analyses of pure versus mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d. ¼ 5.6) versus 28% (s.d. ¼ 12.6, Po0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases, Po0.01); nestin stained 83% (n ¼ 19/23 cases) versus 89% (16/18 cases, P ¼ NS); clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P ¼ NS); SOX10 87% (20/23 cases) versus 94% (17/18 cases, P ¼ NS) and CD271 stained 61% (14/23 cases) versus 67% (12/18 cases, P ¼ NS). Increased CD117 staining in the mixed variant suggests that alterations in the KIT protein may be involved in tumor progression. In addition, the proliferative index of the mixed variant was higher than that of the pure variant.

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“…10 A number of other antibodies have been touted as useful for these tumor types. For example, cytokeratin subsets, especially CK7 and 19, 3,9,14 bcl-2, 15 CD56, 9 calponin, 16 beta-catenin, 17 and matrix metalloproteinase-2 (MMP-2) 18 have been reported as potentially useful in synovial sarcoma; p75 nerve growth factor receptor (NGFR), 19 nestin, 20 CD57, 7,21,22 CD34, 22 PGP9.5, 23 and GFAP 21 in malignant peripheral nerve sheath tumor; Fli-1 in Ewing sarcoma; 6 and neuroectodermal markers such as chromoganin, synaptophysin, and PGP9.5 in primitive neuroectodermal tumor. [24][25][26][27] In order to further characterize the immunohistochemical profiles of synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma in a model that mimics small biopsy sampling, we evaluated a series of 73 tumors in tissue microarrays with a panel of 22 antibodies potentially useful in the differential diagnosis.…”

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confidence: 99%

Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

2006

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As a result of overlapping morphologic and immunohistochemical features, it can be difficult to distinguish synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma/primitive neuroectodermal tumor in core biopsies. To analyze and compare immunohistochemical profiles, we stained tissue microarrays of 23 synovial sarcomas, 23 malignant peripheral nerve sheath tumors, and 27 Ewing sarcomas with 22 antibodies potentially useful in the differential diagnosis, and analyzed the data with cluster analysis. Stain intensity was scored as none, weak, or strong. For CD99, tumors with membranous accentuation were independently categorized. Cluster analysis sorted five groups, with like tumors clustering together. Synovial sarcoma clustered into two groups: one cytokeratin and EMA positive (n ¼ 11), the other mostly cytokeratin negative, EMA positive, bcl-2 positive and mostly CD56 positive (n ¼ 9). Malignant peripheral nerve sheath tumor clustered into two groups: one S100 positive, with nestin and NGFR positivity in most (n ¼ 10), the other mostly S100 negative, and variably but mostly weakly positive for nestin and NGFR (n ¼ 11). Ewing sarcomas clustered into a single group driven by membranous CD99 staining. Thirteen cases failed to cluster (outliers), while three Ewing sarcomas clustered into groups of other tumor types. Paired antibodies for each tumor type determined by visual assessment of cluster analysis data and statistical calculations of specificity, sensitivity, and predictive values showed that EMA/CK7 for synovial sarcoma, nestin/S100 for malignant peripheral nerve sheath tumor, and membranous CD99/Fli-1 for Ewing sarcoma yielded high specificity and positive predictive values. Cluster analysis also highlighted aberrant staining reactions and diagnostic pitfalls in these tumors. Hierarchical cluster analysis is an effective method for analyzing high-volume immunohistochemical data.

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Nestin expression as a new marker in malignant peripheral nerve sheath tumors

Cited by 47 publications

References 25 publications

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

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