Search

Identification of molecular alterations occurring in the adenomatous and carcinomatous components within the same tumor would greatly enhance understanding of the neoplastic progression of colorectal cancer. We examined somatic copy number alterations (SCNAs) and mRNA expression at the corresponding loci involved in the adenoma–carcinoma sequence in the isolated adenomatous and cancer glands of the same tumor in 15 cases of microsatellite‐stable “carcinoma in adenoma,” using genome‐wide SNP and global gene expression arrays. Multiple copy‐neutral loss of heterozygosity events were detected at 4q13.2, 15q15.1, and 14q24.3 in the adenomatous component and at 4q13.2, 15q15.1, and 14q24.3 in the carcinomatous component. There were significant differences in the copy number (CN) gain frequencies at 20q11.21–q13.33, 8q13.3, 8p23.1, and 8q21.2–q22.2 between the adenomatous and carcinomatous components. Finally, we found a high frequency of five genotypes involving CN gain with upregulated expression of the corresponding gene (RPS21, MIR3654, RSP20, SNORD54, or ASPH) in the carcinomatous component, whereas none of these genotypes were detected in the adenomatous component. This finding is interesting in that CN gain with upregulated gene expression may enhance gene function and play a crucial role in the progression of an adenoma into a carcinomatous lesion.

This study aimed to clarify the histological characteristics related to preoperative chemotherapy for colorectal liver metastases (CRLM). Sixty-three patients with CRLM were divided into two groups: CRLM with chemotherapy (41 cases, group A) and CRLM without chemotherapy (22 cases; surgical treatment alone, group S) to identify the histological differences associated with chemotherapy. In addition, we investigated the effects of combination chemotherapy on the histology of metastatic lesions. Infarct-like necrosis (ILN), three-zonal changes, and cholesterol clefts were more frequent in group A than in group S (P < 0.05). ILN and three-zonal changes were more common in the 5-FU with leucovorin and oxaliplatin (FOLFOX), or 5-FU with leucovorin and irinotecan (FOLFIRI) with or without additional bevacizumab groups than in group S (P < 0.05). Cholesterol clefts in the FOLFOX or FOLFIRI with bevacizumab group and foamy macrophages in the FOLFOX or FOLFIRI group were more common than in group S (P < 0.05). Cases with more than three of the four histological findings—i.e. ILN, three-zonal changes, cholesterol clefts, and foamy macrophages—were more frequent in the FOLFOX or FOLFIRI with or without additional bevacizumab groups than in group S (P < 0.05). We showed histological findings for every representative chemotherapy regimen for CRLM to clarify the effects of preoperative chemotherapy.