MET-overexpressing myxofibrosarcoma frequently exhibit polysomy of chromosome 7 but not MET amplification, especially in high-grade cases: clinical and pathological review of 30 myxofibrosarcoma cases

Abstract

Background: Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas. Previous studies have shown that MET protein overexpressed in MFS patients and can serve as a prognostic factor. The reasons for MET protein overexpression include amplification of the MET gene, which is located on chromosome 7q. Triggered by an index case harboring chromosome 7 polysomy rather than MET gene amplification in myxofibrosarcoma, we investigated chromosome 7 polysomy in more cases.

Methods: Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed in 30 MFS cases (including 2 epithelioid variant) to detect the expression of MET protein and gene status.

Results: MET was overexpressed in 14 cases out of 30, while thirteen cases were in higher FNCLCC grades (Grade 2-3). FISH showed that 11 cases having 3 signals on average of Met and more than 3 signals (Mean: 4.6) of centromere 7q (CEP7q). The MET/CEP7 ratio was about 0.65 on average, suggesting that chromosome 7 polysomy, rather than Met gene amplification, leading to the overexpression of MET protein in MFS. MET overexpression and chromosome 7 polysomy are positively correlated with higher Ki-67 index and higher grade and might have a high risk of local recurrence and metastasis.

Conclusions: It might reveals another explain of MET overexpression in myxofibrosarcoma, providing a clue for the therapy of MFS.

Keywords: Chromosome 7 polysomy; FISH; MET; Myxofibrosarcoma.

Fig. 1

Mophology of MFS: Spindle to polygonal sarcoma cells within variably myxoid stroma containing long curvilinear vessels. a: FNCLCC Grade 1 MFS; b: FNCLCC Grade 2 MFS; c: FNCLCC Grade 3 MFS; d: Epithelioid variant of MFS, tumor cells is an infiltrative multinodular growth pattern, with alternation of hypercellular and hypocellular myxoid areas. Tumor cells had epithelioid morphology with abundant eosinophilic cytoplasm and oval or plump spindle nuclei, scattered in the myxoid background (inset).

Fig. 2

MET immunostain shows positive cytoplasm staining in the FNCLCC Grade 2 (a), Grade 3 (b), and Epthelioid MFS (c), while negative expression in FNCLCC Grade 1 MFS (d)

Fig. 3

FISH examination of met gene status by MET (red)/CEP 7(green). Chromosome 7 polysomy, rather than MET amplification, was found in FNCLCC Grade 2 cases (a), Grade 3 cases (b), and epithelioid variant (c). Lower FNCLCC grade cases are usually negative for either MET amplification or chromosome 7 polysomy (d)