FGFR家族受体蛋白在纤维母细胞/肌纤维母细胞性肿瘤中的表达与鉴别诊断价值

Expression and differential diagnosis value of FGFR family proteins in fibroblast/myofibroblast tumors

目的:成纤维细胞生长因子受体(fibroblast growth factor receptor,FGFR)蛋白属于受体酪氨酸激酶家族,含有4种受体亚型(FGFR1,2,3和4)。FGFR激活突变或者配体/受体过表达导致其持续激活与肿瘤的发生、发展、不良预后密切相关。目前,FGFR家族蛋白在纤维母细胞/肌纤维母细胞性肿瘤的表达尚无研究报道。方法:纳入2016-2019年华中科技大学同济医学院附属同济医院手术切除的罕见纤维母细胞/肌纤维母细胞性良、恶性肿瘤共89例,包括17例孤立性纤维肿瘤、16例隆突性皮肤纤维肉瘤(dermatofibrosarcoma protuberans,DFSP),22例侵袭性纤维瘤病,27例未分化肉瘤以及7例结节性筋膜炎(nodular fasciitis,NF)。通过免疫组织化学的方法检测FGFR1,FGFR2,FGFR3,FGFR4蛋白质在组织中的表达水平,通过Fisher’sexacttest统计分析其阳性率差异。结果:未检测到FGFR2和FGFR4在上述纤维母细胞/肌纤维母细胞性肿瘤中的表达。FGFR1高表达于孤立性纤维肿瘤(16/17,94.1%)和DFSP(11/16,68.8%),而在NF和未分化肉瘤中表达均为阴性,FGFR1在孤立性纤维肿瘤、DFSP中表达阳性率与未分化肉瘤相比差异具有统计学意义(P<0.0001),与侵袭性纤维瘤病相比亦具有统计学差异(P<0.0001)。FGFR3在上述纤维母细胞/肌纤维母细胞性肿瘤中均有一定阳性率,阳性率分别为孤立性纤维肿瘤47.1%(8/17)、DFSP68.8%(11/16),侵袭性纤维瘤病86.4%(19/22),未分化肉瘤100%(27/27)以及NF100%(7/7)。结论:免疫组织化学检测FGFR蛋白质的表达有助于孤立性纤维肿瘤、DFSP与未分化肉瘤和侵袭性纤维瘤病的鉴别诊断。通过免疫组织化学检测FGFR蛋白质表达对于纤维母细胞/肌纤维母细胞性肿瘤患者靶向使用FGFR小分子抑制剂具有重要指导意义。

Objective: Fibroblast growth factor receptors(FGFRs) belong to the receptor tyrosine kinase family(RTKs),including four subtypes(FGFR1, 2, 3 and 4). FGFR mutation or overexpression lead to its continuous activation, which is closely related to tumorigenesis, tumor development and patient poor prognosis. However, up to now, the expression of FGFR family proteins in fibroblast/myofibroblast tumors has not been investigated. Methods: Eighty-nine cases of benign and malignant tumors from 2016 to 2019 were collected, including 17 cases of solitary fibrous tumor, 16 cases of dermatofibrosarcoma protuberans(DFSP), 22 cases of aggressive fibromatosis, 27 cases of undifferentiated sarcomas and 7 cases of nodular fasciitis. The expression of FGFR1, FGFR2, FGFR3, FGFR4 protein was detected by immunohistochemistry(IHC), and the difference of positive rate was analyzed by Fisher’s exact test. Results: No expression of FGFR2 or FGFR4 was detected. FGFR1 was highly expressed in solitary fibrous tumor(16/17, 94.1%) and DFSP(11/16, 68.8%), but negative in nodular fasciitis and undifferentiated sarcomas. The positive rate in either solitary fibrous tumor(16/17, 94.1%) or DFSP were significantly different from that in undifferentiated sarcomas and aggressive fibromatosis. The positive staining of FGFR3 was detected in solitary fibrous tumor(8/17, 94.1%), DFSP(11/16, 68.8%), aggressive fibromatosis(19/22, 86.4%), undifferentiated sarcomas(27/27, 100%) and nodular fasciitis(7/7, 100%), respectively. Conclusion: Immunohistochemical staining of FGFR could be helpful in the differential diagnosis of solitary fibrous tumor, DFSP, aggressive fibromatosis, and undifferentiated sarcomas. The detection of FGFR protein expression by immunohistochemistry is important for targeted therapy of FGFR inhibitors.