Oliushina E M, Zavalishina L E, Alekseenok E Yu, Oskina N A, Andreeva Yu Yu, Kuznetsova O A, Filipenko M L, Frank G A
Russian Medical Academy of Continuous Professional Education, Moscow, Russia.
Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
Arkh Patol. 2023;85(2):5-12. doi: 10.17116/patol2023850215.
To study the somatic mutational status of the gene in urothelial bladder cancer (BC) and evaluate its relationship with the clinical and morphological characteristics of the tumor, deficiency of the DNA mismatch repair (dMMR), PD-L1 tumor status, and immunohistochemical (IHC) expression of the p16 protein.
Surgical material of 40 patients with BC, on which the mutational status of the gene was studied using the molecular genetic method, as well as the MMR status, PD-L1 and p16 expression by the IHC method.
mutations, such as G370C, S249C, S371C/Y373C, R248C, were detected in 35.0% of the studied BC samples. FGFR3 status did not depend on the gender and age of patients, as well as on the degree of tumor lymphoid infiltration (TILs). Statistically significant differences were found in the analysis of FGFR3 status depending on the histological structure and degree of tumor differentiation, as well as on the pT stage. The FGFR3 status of BC was not associated with the IHC expression of the studied proteins of the MMR system, as well as with the PD-L1 status. Higher levels of PD-L1 expression were demonstrated by BC tumor cells, in which no aberrations in were detected. There was no significant association between p16 status and the presence of mutations, but for FGFR3-positive carcinomas, the basal pattern of p16 staining by IHC was noted.
A positive somatic mutational status of the gene was statistically significantly more common in the group of papillary low-grade non-muscle-invasive BC, demonstrating basal p16 IHC staining. In the study sample, there was no statistically significant relationship between the FGFR3 status of BC and gender and age differences, TILs, MMR status, PD-L1 status (SP142 and 22C3), and p16 status. The results of the study indicate the need to determine the FGFR3 status in patients with BC for further prescription of personalized therapy.
研究尿路上皮膀胱癌（BC）中该基因的体细胞突变状态，并评估其与肿瘤的临床和形态学特征、DNA错配修复缺陷（dMMR）、PD-L1肿瘤状态以及p16蛋白免疫组化（IHC）表达的关系。
40例BC患者的手术材料，采用分子遗传学方法研究该基因的突变状态，以及通过IHC方法检测MMR状态、PD-L1和p16表达。
在35.0%的研究BC样本中检测到G370C、S249C、S371C/Y373C、R248C等突变。FGFR3状态不依赖于患者的性别和年龄，也不依赖于肿瘤淋巴细胞浸润（TILs）程度。根据组织学结构、肿瘤分化程度以及pT分期分析FGFR3状态时发现有统计学显著差异。BC的FGFR3状态与MMR系统研究蛋白的IHC表达以及PD-L1状态无关。未检测到该基因畸变的BC肿瘤细胞表现出更高水平的PD-L1表达。p16状态与该基因突变的存在之间无显著关联，但对于FGFR3阳性癌，注意到IHC检测p16染色的基底模式。
在乳头状低级别非肌层浸润性BC组中，该基因的体细胞突变阳性状态在统计学上显著更常见，表现为p16 IHC基底染色。在研究样本中，BC的FGFR3状态与性别和年龄差异、TILs、MMR状态、PD-L1状态（SP142和22C3）以及p16状态之间无统计学显著关系。研究结果表明，有必要确定BC患者的FGFR3状态，以便进一步制定个性化治疗方案。
