Title Page
Abstracts
Contents
Introduction 9
Materials and Methods 12
Study population 12
Clinicopathologic evaluation and postoperative surveillance 12
Evaluation of tumor infiltrating lymphocytes 13
DNA extraction 15
Whole exome sequencing 15
Statistical analysis 15
Results 17
Clinicopathological characteristics of patients with synchronous colorectal carcinoma 17
Relationship between tumor location and clinicopathologic characteristics 22
Comparison of clinicopathologic characteristics and oncologic outcomes in the groups divided according to TILs 27
Comparison of clinicopathologic characteristics and oncologic outcomes in the groups divided according to MSI status 30
Mutation analysis of synchronous tumors using WES 36
Discussion 43
Conclusion 48
References 49
Korean Abstracts 54
Table 1. Demographic, clinical, and pathological characteristics 18
Table 2. Comparison of clinicopathologic features of tumors according to MSI status 19
Table 3. Comparison of clinicopathologic features between the index lesions and concurrent lesions 20
Table 4. Clinicopathologic characteristics according to tumor location in SCRC 23
Table 5. Comparison of clinicopathologic characteristics between patients with synchronous tumors located at the same site and at different sites 25
Table 6. Comparison of clinicopathologic features of tumors according to TILs 28
Table 7. Comparison of clinicopathologic characteristics between the groups divided according to MSI status 32
Table 8. Characteristics of tumors analyzed with whole exome sequencing 37
Table 9. Comparison of clinicopathologic characteristics between patients who had tumors with similar mutation burden and different mutation burden 42
Fig. 2. Relationship between the locations of synchronous tumors in each patient. The horizontal axis represents each patient, and the vertical axis represents the distance between... 21
Fig. 3. Survival analysis of subgroups divided according to TILs. (A) Recurrence-free survival (B) Overall survival 29
Fig. 4. Associated family history of 100 patients with synchronous colorectal cancer 31
Fig. 5. Survival analysis in the All MSS, All MSI-H, and MSI-H/MSS groups. (A) Recurrence-free survival and (B) Overall survival in all patients. (C) Recurrence-free survival and (D) Overall survival in stage I-III patients 35
Fig. 6. Mutations identified by whole exome sequencing in 9 patients with 18 synchronous tumors. (A) Single nucleotide variants (B) Insertion or deletion of bases in the genome 38
Fig. 7. The Venn plots of distribution of mutations in patients with SCRC. The number of mutations identified in the index tumor (blue circle), that in the concurrent tumor (red circle), and the number of mutations found in both tumors simultaneously are marked. 39
Fig. 8. Similarity matrix of all mutated genes across the 18 synchronous tumors. The Jaccard coefficient was calculated for each combination of tumors from the same or different patients. 40
Fig. 9. Types of mutations in synchronous tumors. Each square represents a mutated cancer gene in a single tumor, with the color representing the mutation type. The upper panel indicate total mutation burden of each tumor. The blue bars on the right panel indicate the proportions of... 41