Background/Objectives: Colorectal neoplasia developing from ulcerative colitis mucosa (CRNUC) can be divided into ulcerative colitis-associated neoplasia (UCAN) and non-UCAN; however, it is often difficult to distinguish UCAN from non-UCAN during a biopsy diagnosis. We investigated whether a genomic analysis could improve the diagnostic accuracy of UCAN using biopsy specimens. Methods: In step 1, 14 CRNUCs were used to examine whether the genomic landscape of biopsy and resection specimens matched. In step 2, we investigated the relationship between the genomic landscapes and the pathological diagnosis of 26 CRNUCs. The cancer genome was analyzed by deep sequencing using a custom panel of 27 genes found to be mutated in our previous CRNUC analysis. Results: In step 1, of the 27 candidate genes, 14 were mutated. The concordance rate of the pathogenic mutations in these 14 genes between the biopsy and resection specimens was 29% (4/14), while that of the pathogenic mutations inTP53andKRASwas 79% (11/14). In step 2, the pathological diagnosis of biopsy specimens using only hematoxylin and eosin (HE) staining had a sensitivity of 33% and an accuracy of 38% for UCAN diagnosis. On the other hand, the combination of the HE pathology and p53 immunohistochemical staining had a sensitivity of 73% and an accuracy of 85% for UCAN diagnosis, while the combination of HE staining and aTP53mutation had a sensitivity of 87% and an accuracy of 88% for UCAN diagnosis. Conclusions: An evaluation ofTP53mutations in biopsy specimens may be useful for diagnosing UCAN. However, further studies with larger sample sizes are required before this can be applied in clinical practice.
背景/目的：溃疡性结肠炎黏膜来源的结直肠肿瘤（CRNUC）可分为溃疡性结肠炎相关肿瘤（UCAN）与非UCAN；然而，在活检诊断中常难以区分两者。本研究旨在探讨通过活检标本进行基因组分析是否能提高UCAN的诊断准确性。方法：第一步，使用14例CRNUC样本检验活检标本与切除标本的基因组图谱是否一致。第二步，分析26例CRNUC的基因组图谱与病理诊断之间的关系。通过深度测序技术，采用包含27个基因的定制检测面板（这些基因在我们既往的CRNUC研究中被证实存在突变）进行癌症基因组分析。结果：第一步，在27个候选基因中，14个基因检测到突变。活检与切除标本间这14个基因致病突变的一致率为29%（4/14），而TP53与KRAS基因致病突变的一致率达79%（11/14）。第二步，仅使用苏木精-伊红（HE）染色的活检标本病理诊断对UCAN的敏感度为33%，准确率为38%。相比之下，HE病理联合p53免疫组化染色对UCAN的诊断敏感度提升至73%，准确率达85%；而HE染色联合TP53突变检测的诊断敏感度达87%，准确率为88%。结论：活检标本中TP53突变的评估可能有助于UCAN的诊断，但该方法应用于临床前仍需更大样本量的进一步研究验证。
Genetic Analysis of Biopsy Tissues from Colorectal Tumors in Patients with Ulcerative Colitis
肿瘤(癌症)患者之家