Study of the Lymphonodular Metastasizing Patterns of Colorectal Carcinoma (Crc) in Microsatellite-Instability (Msi) Context

Introduction Lymphonodular metastasis of CRC is a prognostic factor that plays an important role in implementing the individualized CRC treatment strategies [1]. Microsatellites (MS) are short repeating DNA fragments, and CRC with unstable MS (MSI) demonstrates a more effective response to immune checkpoint inhibitor therapy [2]. Considering improving CRC therapy based on morphological diagnostics and molecular testing, accurate morphologic diagnostic information of the lymphonodular metastasizing patterns of CRC in MSI context is relevant. Aim Study aim is to determine the lymphonodular metastasizing patterns of CRC in MSI context. Methods A morphological analysis of 225 colorectal surgical specimens received to CRC pathology diagnostic processing in 2019 – 2023 was carried out. Morphological analysis of primary neoplasia (pT), local lymphogenic metastases (pN), distant metastasis (pM) was accomplished by light microscopy (TNM classification, 5th ed.). Immunohistochemical reactions against MLH1 (M1 clone), PMS2 (A16-4 clone), MSH2 (G219-1129 clone), and MSH6 (SP93 clone) for MSI status were performed and evaluated. Statistical analysis, including descriptive statistics (median, minimal and maximal values, frequencies), Mann-Whitney U test, χ2 test, was performed by SPSS 29.0 software (p<0.05). Results 125 men and 100 women of similar age (median – 66 years old (y.o.), min. – 28 y.o., max. – 92 y.o. and median – 69 y.o., min. – 29 y.o., max. – 89 y.o.; U=6492, p=0.618) were included into the study. Most of CRC cases were pT3 (n=211, 93.8%). There were no local lymphonodular metastases (pN0) in 91.6% cases (n=206). 8.4% (n=19) of CRC cases had distant metastases (pM1). Immunohistochemical MSI status was detected in 22.7% (n=51) CRC cases. Lymphonodular metastasizing was more likely to be detected among younger patients (medians of pN0 vs. pN>0 cases – 68 y.o. vs. 60 y.o, U=1258, p=0.01), pT4a (10.5%, χ2=46.426, p<0.001), and pM1 (4.4%, χ2=52.409, p<0.001) CRC cases. Lymphonodular metastasizing was similar among gender (χ2=0.072, p=0.813) and MS-stable (MSS) vs. MSI status of CRC (χ2=1.745, p=0.257). Conclusions CRC metastases in local lymph nodes were more likely to be detected in younger CRC patients, with pT4a and pM1 categories among CRC cases with immunohistochemically examined MSI status. Local lymphonodular metastasizing was similar among MSS and MSI CRC cases, implying that far more complex oncogenetic mechanisms (compared to MSI) may affect CRC lymphonodular metastasizing process.