Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
J Clin Pathol. 2018 Oct;71(10):865-873. doi: 10.1136/jclinpath-2018-205002. Epub 2018 Apr 25.
The aim of our study was to analyse correlations between mutation status, chromosomal changes that affect status in cells from pancreatic tumours.
We collected 69 cases of surgically resected pancreatic ductal adenocarcinoma (PDA) and seven cases of chronic pancreatitis (CP). Chromosomal abnormalities of and CEP12 were detected using fluorescence in situ hybridisation (FISH).
The number of CEP12 signals per cell ranged from 1.78 to 2.04 and 1.46 to 4.88 in CP and PDA samples, respectively, while the number of signals per cell ranged from 1.94 to 2.06 and 1.88 to 8.18 in CP and PDA samples, respectively. The 'chromosomal instability index', which was defined as the percentage of cells with any chromosomal abnormality, was over 5.7 times greater in PDA than in CP. We performed mutation analysis by direct sequencing and found that tumours with mutations have a significantly higher mean signal per cell from PDA samples compared with tumours with wild-type amplification was noted in 10% of cases. Although we found that lymph node metastasis and distal metastasis of PDA were more frequent in cases with amplification, this was not correlated with overall survival. Using a threshold of 40%, we found that the chromosomal instability index robustly discriminated PDA cells from CP cells.
Based on these findings, we concluded that FISH testing of using cytology samples may represent an accurate approach for the diagnosis of PDA.
我们的研究旨在分析胰腺肿瘤细胞中 突变状态与影响 状态的染色体变化之间的相关性。
我们收集了 69 例手术切除的胰腺导管腺癌(PDA)和 7 例慢性胰腺炎(CP)病例。使用荧光原位杂交(FISH)检测 和 CEP12 的染色体异常。
CEP12 信号的细胞数分别为 CP 和 PDA 样本中的 1.78-2.04 和 1.46-4.88,而 信号的细胞数分别为 CP 和 PDA 样本中的 1.94-2.06 和 1.88-8.18。“染色体不稳定性指数”定义为具有任何染色体异常的细胞百分比,在 PDA 中比 CP 高 5.7 倍以上。我们通过直接测序进行了 突变分析,发现 PDA 样本中具有 突变的肿瘤的平均 信号细胞数明显高于具有野生型 扩增的肿瘤。在 10%的病例中观察到 扩增。尽管我们发现 PDA 中的淋巴结转移和远端转移在 扩增病例中更为频繁,但这与总生存期无关。使用 40%的阈值,我们发现染色体不稳定性指数能够可靠地区分 PDA 细胞和 CP 细胞。
基于这些发现,我们得出结论,使用细胞学样本进行 FISH 检测 可能代表诊断 PDA 的一种准确方法。