Microtubule-Associated Protein-2 and Class III β-Tubulin Are Expressed in Extraskeletal Myxoid Chondrosarcoma

Abstract

Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma of uncertain histogenetic origin. Because recent reports have indicated neural-neuroendocrine differentiation in some extraskeletal myxoid chondrosarcomas, we investigated 25 tumors for expressions of microtubule-associated protein-2 and Class III ␤-tubulin, which are major components of microtubules and specifically localized in neurons and their derivatives. Immunohistochemical expression of microtubule-associated protein-2 and Class III ␤-tubulin was studied in extraskeletal myxoid chondrosarcomas using formalin-fixed, paraffin-embedded tissues. Cytoplasmic expressions of microtubule-associated protein-2 and Class III ␤-tubulin were detected in 21 (84%) and 13 (52%) of the 25 extraskeletal myxoid chondrosarcomas, respectively, although the number of positively stained tumor cells varied. Expression of the Class III ␤-tubulin gene was also assessed in two immunohistochemically positive cases by in situ hybridization using an oligonucleotide probe specific for its transcript, and both cases showed expression of Class III ␤-tubulin transcript.Another case was examined with immunoelectron microscopy, and immunogold particles for Class III ␤-tubulin were localized to microtubular aggregates. Our data indicate that microtubules in extraskeletal myxoid chondrosarcoma are similar to those found in neurons, further supporting the concept that neural-neuroendocrine differentiation occurs in a significant number of extraskeletal myxoid chondrosarcoma. Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma with distinct clinicopathologic and cytogenetical features (1-8). It is typically myxoid and arises in the deep soft tissue of the proximal extremities and limb girdles of middle-aged adults (1-4). Characteristic chromosomal translocations including t(9;22)(q22;q12), resulting in a fusion of the EWS gene at 22q12 and the CHN/TEC gene at 9q22, have been reported in extraskeletal myxoid chondrosarcoma, as well as two other less common rearrangements, including fusion of the EWSrelated gene TAF2N to CHN/TEC and fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to CHN/TEC (5-8). Extraskeletal myxoid chondrosarcoma has generally been regarded as a chondroid tumor because of morphologic similarities between extraskeletal myxoid chondrosarcoma and embryonic chondrogenesis, the presence of chondroitin-4 and 6-sulfate in its myxoid matrix, frequent S-100 protein positivity, and Type II collagen synthesis by tumor cells (1, KEY WORDS: Extraskeletal

Extraskeletal myxoid chondrosarcoma

“…These fusion products are postulated to modify transcriptional activity and regulate cellular differentiation and growth, leading to tumorigenesis 16–18,25. Ultrastructural studies of EMC have also uncovered evidence of markers of neuroendocrine differentiation7,8 such as class III β-tubulin and microtubule-associated protein-2 9. These findings argue against a chondrocytic or prechondrocytic origin of this malignancy, and further distinguish EMC as a unique entity among sarcomas.…”

TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma

“…Histologically, the lesion was characterized by lobular configurations of a proliferation of short spindle or oval cells arranged mainly in a lacelike fashion or partially in a loose fascicular pattern with an abundant myxoid matrix. Immunohistochemically, the tumor showed features of neural/neuroendocrine differentiation; neuron-specific enolase, synaptophysin, protein gene product 9.5 (PGP9.5), peripherin, and microtubule-associated protein (MAP)-2 were positive, whereas S-100 protein, cytokeratin, epithelial membrane antigen, muscle actins, and desmin were negative (Okamoto et al, 2001;Hisaoka et al, 2003).…”

“…To address this possibility, we performed reverse transcription-polymerase chain reaction (RT-PCR) using RNA extracted from snap-frozen and/or formalin-fixed, paraffin-embedded tissues of four EMCs in which no transcripts of previously described NOR1 fusions could be detected (Okamato et al, 2001;Hisaoka et al, 2003).…”

Clinicopathological features of extraskeletal myxoid chondrosarcoma: An analysis of 9 cases

“…EMC has recently been shown to frequently express class III β-tubulin and microtubuleassociated protein-2 immunohistochemically, the former of which was also demonstrated to localize to the aggregated microtubules immunoelectron microscopically [22] . Such constituent or associated proteins of microtubules are known to be restricted almost entirely to neurons and their derivatives with some minor exceptions such as Sertoli cells and hair follicles [24] .…”

“…A novel finding recently has been the reported expression of microtubule-associated protein-2 and Class III β-tubulin of EMC. Cytoplasmic expressions of microtubule-associated protein-2 and Class III β-tubulin were detected in 21 (84%) and 13 (52%) of the 25 extraskeletal myxoid chondrosarcomas, respectively [22] . It provides additional support for the notion of neural differentiation in EMC.…”