Background:Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes.Methods:This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic databases were used for mutational correlation analysis.p-value ≤ 0.05 was considered as significant.Results:A total of thirty-nine patients with resected IPMN with complete clinical and sequencing data were identified and included in the final cohort. The male-to-female distribution was 21:18, and the mean age was 70.1 ± 9.1 years. GNAS mutations occurred in 23.1% of patients, and 89.7% of patients had iIPMN. In iIPMN patients, GNAS mutation was strongly associated with improved disease-free survival: all GNAS-mutant patients survived to follow-up with significantly fewer recurrences than in GNAS wild-type (WT) patients (p= 0.013). Mutated GNAS closely co-occurred with wild-type KRAS (p< 0.001), and further analysis of large genomic PDAC datasets validated this finding (OR 3.47,p< 0.0001).Conclusions:Our study suggests prognostic value of mutational status in malignant resected IPMNs. WT GNAS, mutant P53, and mutant KRAS each correlate with recurrence and decreased survival. Further studies are required to validate these preliminary observations.
背景：导管内乳头状黏液性肿瘤（IPMNs）是胰腺的癌前病变，可能进展为侵袭性胰腺导管腺癌（PDAC）。与非IPMN来源的PDAC相比，IPMN相关侵袭性癌（iIPMN）与更良好的生存预后相关。本研究旨在探讨IPMNs的基因图谱，以评估其与肿瘤学预后的相关性。 方法：本回顾性研究采用了一个大型单中心前瞻性维护数据库。纳入2016年至2022年间接受根治性胰腺切除术且经组织学确诊为IPMN的患者。记录人口统计学、病理学、分子学及肿瘤学预后数据。采用Kaplan-Meier法进行生存分析，并使用公共基因数据库中的PDAC数据进行突变相关性分析。p值≤0.05被认为具有统计学意义。 结果：共39例接受切除术的IPMN患者被纳入最终队列，这些患者具有完整的临床和测序数据。男女比例为21:18，平均年龄为70.1±9.1岁。23.1%的患者存在GNAS突变，89.7%的患者为iIPMN。在iIPMN患者中，GNAS突变与改善的无病生存期显著相关：所有GNAS突变患者均存活至随访结束，其复发率显著低于GNAS野生型（WT）患者（p=0.013）。突变型GNAS与野生型KRAS密切共存（p<0.001），对大型基因组PDAC数据集的进一步分析验证了这一发现（OR 3.47，p<0.0001）。 结论：我们的研究表明，在恶性切除的IPMNs中，突变状态具有预后价值。野生型GNAS、突变型P53和突变型KRAS均与复发和生存期降低相关。需要进一步的研究来验证这些初步观察结果。
肿瘤(癌症)患者之家