Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea.
Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea.
Sci Rep. 2023 Oct 2;13(1):16547. doi: 10.1038/s41598-023-42386-6.
Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3-49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04-3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11-3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19-9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23-4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.
壶腹腺癌患者的预后结果各不相同，这可能是由于这些恶性肿瘤可以起源于该部位的三种汇聚上皮中的任何一种。这种变异性给临床决策过程和治疗方法的制定带来了困难。在这项研究中，通过整合组织病理学分析与蛋白表达（MUC1、CDX2、CK20 和 MUC2），对接受根治性手术切除的 87 例 IB 至 III 期壶腹腺癌患者的潜在临床价值进行了评估。在这 87 名患者中，54 名被归类为胰胆管（PB）亚型，33 名被归类为肠型。所有患者的中位随访时间为 32.8 个月（95%CI，25.3-49.2）。具有组织分子 PB 表型（CDX2 阴性、MUC1 阳性、MUC2 阴性，无论 CK20 结果如何）的患者在无病生存率（DFS）（HR=1.81；95%CI，1.04-3.17；p=0.054）和总生存率（OS）（HR=2.01；95%CI，1.11-3.66；p=0.039）方面的预后均较差。与肠型相比，PB 型患者更易出现局部复发（37 例中有 11 例，29.7%），而肠型仅有 1 例（15 例中有 1 例，6.7%）。在全身性疾病的情况下，与肠型相比，PB 型患者中观察到更高比例的患者出现升高的癌抗原 19-9 水平（p=0.024）。在接受一线姑息性化疗的 38 名患者队列中，与肠型相比，PB 型患者的中位总生存期（OS）明显缩短（10.3 个月 vs. 28.3 个月，HR=2.47；95%CI，1.23-4.95；p=0.025）。通过整合组织病理学和分子标准，我们可以在壶腹腺癌中识别出独特且具有临床意义的组织分子表型，这可能对现有的治疗方法产生重大影响。
