Correlation of NTRK genetic fusions with mismatch repair protein deletion in patients with colorectal cancer.
10.3760/cma.j.cn112151-20210716-00512
- VernacularTitle:结直肠癌中错配修复蛋白缺陷与NTRK基因融合的相关性分析
- Author:
Xiao Hong PU
1
;
Fu Ping GAO
2
;
Hong Yan WU
1
;
Yao FU
1
;
Xiang Shan FAN
1
Author Information
1. Department of Pathology, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
2. Department of Pathology, Gaochun People's Hospital Branch, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Gaochun 211300, China.
- Publication Type:Journal Article
- MeSH:
Colonic Neoplasms;
Colorectal Neoplasms/genetics*;
DNA Mismatch Repair/genetics*;
Humans;
In Situ Hybridization, Fluorescence;
Mismatch Repair Endonuclease PMS2/metabolism*;
MutL Protein Homolog 1/metabolism*;
MutS Homolog 2 Protein/metabolism*
- From:
Chinese Journal of Pathology
2022;51(2):103-107
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the relationship between the expression of four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) and NTRK genetic fusions in colorectal cancer. Methods: The paraffin-embedded tissue blocks of 830 cases of colorectal cancer were collected at the Affiliated Drum Tower Hospital, Nanjing University Medical School, China, from 2015 to 2019. Immunohistochemical and fluorescence in situ hybridization(FISH) method were used respectively to detect the expression of mismatch repair proteins and the break-apart of NTRKs; and the relationship between the expression of mismatch repair proteins and the NTRK genetic fusions was analyzed. Results: The overall mismatch repair protein deficiency (dMMR) rate was 9.88% (82/830), the mismatch repair proteins proficiency (pMMR) rate was 90.12%(748/830). The total deficiency rate of MLH1 protein was 9.04% (75/830), hPMS2 protein deficiency rate was 9.04% (75/830), MSH2 protein deficiency rate was 2.53% (21/830), MSH6 protein deficiency rate was 4.10% (34/830), the deficiency rate of synchronous MLH1 and PMS2 were 8.67% (72/830) and the deficiency rate of synchronous MSH2 and MSH6 were 2.17% (18/830). The dMMR group was associated with tumor location, different histological subgroups, tumor differentiation, AJCC stage and N stage (P<0.05). There were six cases (7.32%) carrying NTRK fusion by FISH among the 82 cases of dMMR, but only seven cases (0.94%) carrying NTRK fusion among the 748 cases of PMMR. The NTRKs translocation by FISH in all 13 cases were further confirmed by next generation sequencing. Among the clinicopathological characteristics, only differentiation showed significant difference between NTRK fusion positive and negative groups (P<0.05). More importantly, NTRK fusion was enriched in dMMR group (7.32% vs. 0.94%). Conclusion: In dMMR colorectal cancer group, the prevalence of NTRK fusion is higher than that in pMMR group.
