Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal.
Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.
Dig Dis Sci. 2018 Sep;63(9):2351-2361. doi: 10.1007/s10620-018-5128-y. Epub 2018 May 24.
Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas.
To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making.
We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing.
There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst.
In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing.
胰腺囊肿是常见的偶发病变，具有恶性潜能，这引发了诊断和治疗方面的难题。
确定 KRAS 和 GNAS 基因突变分析对囊肿分类和决策的附加价值。
我们分析了 2008 年至 2014 年间通过 EUS-FNA 获得的 52 例胰腺囊性液冷冻样本。除了细胞学和 CEA 检测外，还使用 Sanger 测序分析了 GNAS（外显子 8 和 9）和 KRAS（外显子 2 和 3）基因突变。
共纳入 52 例患者（67%为女性），平均年龄为 59±15 岁（29-91 岁）。21 例（40%）患者的囊肿为黏液性，14 例为低危，7 例为恶性；31 例（60%）患者的囊肿为非黏液性。EUS-FNA 后，11 例患者接受了手术，6 例接受了化疗或姑息治疗，1 例接受了内镜引流，34 例患者在平均 57 个月的随访后仍在继续治疗。9 例样本中检测到 KRAS 突变，2 例样本中检测到 GNAS 突变。携带 KRAS 突变的患者年龄更大（p=0.01），囊肿更常见为黏液性（p=0.001）且恶性程度更高（p=0.01）。KRAS 突变存在于低危和恶性黏液性病变中。对于识别黏液性病变，CEA＞192ng/mL 的检测效能更好（AUC ROC=93%），而对于恶性/高危黏液性病变，EUS 成像的准确性最高（AUC ROC=88%）。经过分子分析，10 例患者的囊肿分类发生了改变，但仅有 2 例改变是正确的，即一个假性囊肿被重新归类为 IPMN，一个恶性囊肿被归类为非黏液性囊肿。
在本胰腺囊肿患者队列中，与传统检测相比，KRAS 和 GNAS 基因突变在诊断方面没有显著获益。
