作者
A. A. Musaelyan,С. В. Лапин,В. Д. Назаров,S. L. Vorobyev,А. А. Захаренко,Sergey Orlov
摘要
Solid tumors with microsatellite instability (MSI), regardless of location, are highly susceptible to immune checkpoint inhibitors. The aim of the study was to investigate clinical and morphological features of tumors with MSI. The study included 787 tumor samples of the following localizations: 530- colorectal cancer (CRC), 95- endometrial carcinoma (EC), 87- gastric cancer (GC), 20- ovarian cancer, 18- pancreatic cancer, 15- cervical cancer, 15- esophageal cancer, 7- cancers of unknown primary site. The study of MSI was carried out using fragment analysis by determining mononucleotide markers: BAT-25, BAT-26, NR-21, NR-24, NR-27. Data of preoperative level of CEA and CA19-9 were obtained in 185 patients with CRC. The prevalence of MSI in CRC was 6.8%, in EC- 27.4%, in GC - 6.9%, in ovarian cancer - 5%. MSI was not found in other localizations. The characteristic clinical and morphological features of MSI-positive CRC were younger age (p=0.032), right-sided localization (p<0.0001), presence of multiple primary tumors (p=0.041), absence of distant metastases (p=0.013), presence of carcinoma G3 (p=0.0008), mucinous component (p<0.0001), Crohn-like reaction (p=0.0063) and tumor-infiltrating lymphocytes (p<0.0001). Also, in patients with CRC with MSI, the preoperative level of CEA was lower than in patients with MSS tumors: the median was 2.0 ngml (interquartile range (IQR): 0.7-3.4; n=20) and 3.9 ng/ml (IQR: 1.1-13.1; n=165), respectively (p=0.0061). No differences in smoking status, tumor size and the presence of diseases associated with an increase of CEA were shown between the MSI and MSS CRC. For EC with MSI, there were the following features: endometrioid adenocarcinoma (p=0.017), high grade tumors (p=0.0054), presence of cribriform growth pattern (p=0.0084) and tumor-infiltrating lymphocytes (p=0.0019), as well as a higher level of mitotic activity (p=0.002). MSI-positive GC was more often found in women (p=0.033), was characterized by older age (p=0.001), distal tumor localization (p=0.022), presence of high-grade tumors (p=0.012) and tumor-infiltrating lymphocytes (p=0.009). Common features for CRC, EC and GC with MSI are the presence of a high-grade tumors and tumor-infiltrating lymphocytes.