Kim Juwan, Hong Seung Soo, Kim Sung Hyun, Hwang Ho Kyoung, Hong Namki, Rhee Yumie, Kang Chang Moo
Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Pancreatology. 2025 Feb;25(1):134-141. doi: 10.1016/j.pan.2024.11.020. Epub 2024 Nov 29.
Pancreatic neuroendocrine tumors (PNETs) are the leading cause of death related to multiple endocrine neoplasia type 1 (MEN1). Previous studies have linked certain mutations in the MEN1 gene and loss of interactions with MENIN's functional partners to the mortality or aggressiveness of PNETs. This study aimed to evaluate the genotype-phenotype correlations of MEN1-related PNETs in Korean patients and to summarize the treatment outcomes comprehensively.
We retrospectively analyzed 72 patients diagnosed with MEN1 at a tertiary care center in Korea between January 2003 and September 2022. MEN1 mutations were analyzed using direct or next-generation sequencing.
Among 40 families with MEN1, 10 had exon 2 mutations, which were the most frequently observed. Of these, 50 (69.4 %) were diagnosed with PNETs; 20 underwent pancreatic resection. Patients with truncating mutations showed a significant difference in age-related penetrance of PNET (p = 0.029). No distinct genotype was associated with malignant transformation (lymph node or distant metastasis) in MEN1-related PNETs. In the subgroup Cox model, mutations in exons 3 or 10 showed significant differences in tumor progression in the observation group (adjusted hazard ratio: 8.164,(95 % CI: 1.648-40.436), p = 0.010, HR: 8.300, (95 % CI: 1.808-38.113), p = 0.007).
PNETs in Korean patients with MEN1 exhibit a stable prognosis. An individualized follow-up strategy may be necessary, particularly for young patients with truncating mutation in the MEN1 gene. In addition, those with mutations in exons 3 or 10 may require more active surveillance to decrease the risk of progression.
胰腺神经内分泌肿瘤（PNETs）是与1型多发性内分泌腺瘤病（MEN1）相关的主要死亡原因。先前的研究已将MEN1基因中的某些突变以及与MENIN功能伙伴相互作用的丧失与PNETs的死亡率或侵袭性联系起来。本研究旨在评估韩国患者中MEN1相关PNETs的基因型与表型的相关性，并全面总结治疗结果。
我们回顾性分析了2003年1月至2022年9月在韩国一家三级医疗中心诊断为MEN1的72例患者。使用直接测序或下一代测序分析MEN1突变。
在40个患有MEN1的家族中，10个有外显子2突变，这是最常见的。其中，50例（69.4%）被诊断为PNETs；20例接受了胰腺切除术。截断突变患者在PNET的年龄相关外显率方面存在显著差异（p = 0.029）。在MEN1相关的PNETs中，没有明显的基因型与恶性转化（淋巴结或远处转移）相关。在亚组Cox模型中，外显子3或10的突变在观察组的肿瘤进展方面存在显著差异（调整后的风险比：8.164，（95%置信区间：1.648 - 40.436），p = 0.010，风险比：8.300，（95%置信区间：1.808 - 38.113），p = 0.007）。
韩国MEN1患者的PNETs预后稳定。可能需要个体化的随访策略，特别是对于MEN1基因有截断突变的年轻患者。此外，外显子3或10有突变的患者可能需要更积极的监测以降低进展风险。
