18例孤立性纤维瘤的临床病理特点分析及蛋白质组学探索

Clinicopathological characteristics and proteomic study of 18 cases of solitary fibrous tumors

目的:研究孤立性纤维瘤患者的复发特点及每次手术标本的病理特点,分析孤立性纤维瘤的生物学行为特点,以便为患者选择最佳的治疗方案,以期获得更大的临床收益和更长生存时间。方法:回顾性研究2011年11月01日至2019年05月31日于我院住院行孤立性纤维瘤切除手术的18例患者的临床和病理资料(3例曾在外院手术者借阅既往病历资料和病理标本切片),综合分析患者的临床资料和病理特点。比较16份孤立性纤维瘤标本肿瘤微环境蛋白质组学构成变化。结果:随访期间18例患者手术后的生存时间从1个月到213个月,平均生存时间为57.9个月。6例复发后再手术者中,3例死于疾病进展,2例带瘤生存,1例治愈,手术次数2~5次。6例复发后再手术者中,有5例为2次及以上复发者,其中4例复发间隔时间递减。6例复发后再手术者中,随着复发次数的增多,肿瘤细胞核分裂象明显增加,Ki-67阳性率明显增加,病理结果逐步由良性转为交界性,甚至恶性。提示复发性孤立性纤维瘤患者的肿瘤细胞随着手术次数的增加,恶性程度也在随之增加。4个因为肿瘤进展而死亡的病例肿瘤均来源于腹腔和盆腔。蛋白质组学研究发现,肿瘤中的processing of RNA和splicing of RNA相关蛋白上调表达,肿瘤微环境中的中性粒细胞相关蛋白表达水平上升。结论:孤立性纤维瘤手术后容易复发,随手术次增加,其复发间隔变短,并且恶性程度递增。延长复发后的观察时间,尽量减少手术次数,可能达到患者更优的生存收益。腹腔和盆腔来源的孤立性纤维瘤呈现更多侵袭性,容易造成死亡。孤立性纤维瘤有可能分泌促进自身生长的因子,或者肿瘤切除之后人体合成的促进细胞组织和生物生发的激素明显下降。蛋白质组学研究结果分析发现,手术创伤引起的炎症反应,导致免疫相关蛋白在病灶处富集,并在肿瘤富集形成大量的毛细血管从而导致肿瘤细胞的增殖与转移。

Objective:To study the recurrence characteristics of patients with solitary fibrous tumors and the pathological characteristics of each surgical specimen,and to analyze the biological behavior characteristics of solitary fibrous tumors,so as to select the best treatment for patients,so as to obtain greater clinical benefits and longer survival time.Methods:The clinical and pathological data of 18 patients who underwent resection of solitary fibrous tumors in our hospital from November 1,2011 to May 31,2019 were retrospectively studied(3 patients who had been operated in other hospital borrowed medical records and pathological specimens).The clinical data and pathological features were analyzed comprehensively.The proteomic changes of tumor microenvironment in 16 solitary fibrous tumors were compared.Results:During the follow-up period,the survival time of 18 patients after operation ranged from 1 month to 213 months,with an average survival time of 57.9 months.Among the 6 patients who underwent reoperation after recurrence,3 died of disease progression,2 patients survived with tumors,and 1 patient was cured.The times of operations ranged from 2 to 5.Among the 6 patients who underwent reoperation after recurrence,5 patients had 2 or more recurrences,of which 4 patients had a decreasing interval of recurrence.Among the 6 patients who underwent reoperation after recurrence,with the increase of recurrence times,the mitotic image and the positive rate of Ki-67 increased significantly.The pathological results gradually changed from benign to borderline or even malignant.It was suggested that the malignant degree of the tumor specimens in patients with recurrent solitary fibrous tumors increases with the times of operations.The tumors of 4 patients who died as a result of the progression of the tumors all originated from the abdominal cavity and pelvic cavity.Proteomic studies found that the expression of processing of RNA and splicing of RNA-related proteins in tumors was up-regulated,and the expression level of neutrophil-related proteins in tumor microenvironment was increased.Conclusion:Solitary fibrous tumors is prone to recurrence after surgery.The more reoperations,the shorter the recurrence interval,and the degree of malignancy increases with the times of operations.Extending the observation time after recurrence and minimizing the times of operations may achieve better survival benefits for patients.Solitary fibrous tumors from abdominal and pelvic sources is more invasive and prone to death.Solitary fibrous tumors may secrete growth-promoting factors,or the hormones synthesized by the human body to promote cell tissue and biogenesis significantly decrease after tumor resection.The analysis of proteomic research results found that the inflammatory reaction caused by surgical trauma led to the enrichment of immune-related proteins in the focus and the formation of a large number of capillaries in the tumor,leading to the proliferation and metastasis of tumor cells.