Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins. We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017–2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes. Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352–9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019). Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.

中文翻译：

---

分子手术切缘分析对胰十二指肠切除术后胰腺癌复发预测的影响


胰腺癌是实体恶性肿瘤中致命的癌症之一。由于组织萎缩、看不见的野癌化和肿瘤出芽等跳过病变，手术切缘的病理诊断有时不可靠。因此，有时甚至在病理阴性的手术切缘处也会发生肿瘤复发。我们通过组织印迹程序应用分子手术切缘（MSM）分析，以提高胰十二指肠切除术后手术标本表面微小癌细胞的检测灵敏度。手术标本采集自 2017-2019 年在名古屋大学医院接受保胃次全胰十二指肠切除术的 45 例胰腺癌病例。对原始甲基化标记物组（CD1D、KCNK12、PAX5）进行定量甲基化特异性 PCR (QMSP)，并分析术后生存结果。在 45 个肿瘤中，26 例（58%）CD1D QMSP 阳性，25 例（56%）KCNK12 阳性，27 例（60%）PAX5 阳性。在这三种标志物中至少一种呈阳性的38个肿瘤中，在手术切缘处检测到CD1D阳性癌细胞、KCNK12阳性癌细胞和PAX5阳性癌细胞的有8例、7例和10例，分别。因此，共有 17 名患者在手术切缘处通过 QMSP 检测到至少一种标记物，这些患者被定义为 MSM 阳性。与 MSM 阴性患者相比，它们的无复发生存期 (p = 0.002) 和总生存期 (p = 0.005) 显着较差。多变量分析显示，MSM 阳性是无复发生存率较差的唯一显着独立因素（风险比：3.522，95% 置信区间：1.352–9.179，p = 0.010）。 另一方面，很大一部分 MSM 阴性病例接受了新辅助化疗 (p = 0.019)。建立胰腺癌特异性甲基化标记物组以进行 MSM 分析。 MSM 阳性状态可能代表手术切缘上显微镜无法检测到的癌细胞，并可能影响术后的长期结果。