PO.CL01.17 · 临床研究
伴神经内分泌分化的结直肠癌的临床病理及预后分析
Clinicopathological and prognostic analyses of colorectal cancer with neuroendocrine differentiation
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：一部分结直肠癌（CRC）表现出神经内分泌分化（NED），其特征为表达突触素和嗜铬粒蛋白A等神经内分泌标志物。尽管NED在其他癌症类型中已被报道与侵袭性行为和不良预后相关，但由于证据有限且不一致，NED在CRC中的临床病理和预后意义仍不明确。更好地理解伴NED的CRC可能为其分子特征和潜在治疗策略提供见解。
方法：回顾性分析了2013年至2017年间在我院接受手术切除的病理分期II-IV期CRC患者。对福尔马林固定石蜡包埋组织切片进行突触素免疫组化染色。当突触素H评分≥4时，NED定义为阳性。比较NED阳性组与NED阴性组之间的临床病理特征，包括淋巴管血管和神经周围浸润、促结缔组织增生反应模式、肿瘤出芽分级和低分化簇（PDC）分级。使用Kaplan-Meier方法分析总生存期（OS）和无复发生存期（RFS）。
结果：在261例可评估的CRC病例中，21例（8.0%）基于突触素表达被分类为NED阳性。NED阳性组包括9例男性和12例女性，中位年龄68岁（范围17-91岁）。TNM分类（第8版）如下：病理II期（n=4，各期总例数的4.1%）、III期（n=10，9.3%）和IV期（n=7，12.5%）。与NED阴性CRC相比，NED阳性组更频繁地表现出以下特征：神经周围浸润（61.9% vs. 31.3%）、高级别肿瘤出芽（G2/G3：61.9% vs. 33.8%）和PDC（G2/G3：47.6% vs. 21.3%）。NED阳性组的中位OS和RFS分别为78个月和28个月。NED阳性组的5年OS和RFS率分别为71.9%和35.3%，而NED阴性组分别为75.1%和67.1%。伴NED的CRC的RFS显著短于不伴NED者（log-rank检验，p=0.0073）。
结论：NED的存在倾向于与神经周围浸润和高级别PDC相关，提示更具侵袭性的组织病理学特征的趋势。伴NED的CRC的RFS显著短于不伴NED者，表明NED与早期复发之间可能存在关联。
查看英文原文 English abstract
Background: A subset of colorectal cancers (CRCs) exhibits neuroendocrine differentiation (NED), characterized by the expression of neuroendocrine markers such as synaptophysin and chromogranin A. Although NED has been reported to be associated with aggressive behavior and poor prognosis in other cancer types, the clinicopathological and prognostic significance of NED in CRC remains unclear due to limited and inconsistent evidence. A better understanding of CRC with NED may provide insights into its molecular characteristics and potential therapeutic strategies.
Methods: Patients with pathological stage II-IV CRC who underwent surgical resection at our institution between 2013 and 2017 were retrospectively analyzed. Immunohistochemical staining for synaptophysin was performed on formalin-fixed, paraffin-embedded tissue sections. NED was defined as positive when the H-score for synaptophysin was ≥4. Clinicopathological features-including lymphovascular and perineural invasion, desmoplastic reaction pattern, tumor budding grade, and poorly differentiated cluster (PDC) grade-were compared between NED-positive and NED-negative groups. Overall survival (OS) and relapse-free survival (RFS) were analyzed using Kaplan-Meier method.
Results: Among 261 evaluable CRC cases, 21 (8.0%) were classified as NED-positive based on synaptophysin expression. The NED-positive group included 9 males and 12 females, with a median age of 68 years old (range, 17-91 years old). The TNM classification (8th edition) was as follows: pathological stage II (n=4, 4.1%), stage III (n=10, 9.3%), and stage IV (n=7, 12.5%) of the total cases in each stage. Compared with NED-negative CRCs, the NED-positive group more frequently exhibited the following features: perineural invasion (61.9% vs. 31.3%), high-grade tumor budding (G2/G3: 61.9% vs. 33.8%) and PDC (G2/G3: 47.6% vs. 21.3%). The median OS and RFS for the NED-positive group were 78 months and 28 months, respectively. The 5-year OS and RFS rates were 71.9% and 35.3% in the NED-positive group, compared with 75.1% and 67.1% in the NED-negative group, respectively. RFS was significantly shorter in CRCs with NED than in those without (log-rank test, p=0.0073).
Conclusions: The presence of NED tended to be associated with perineural invasion and high-grade PDC, suggesting a trend toward more aggressive histopathological features. RFS was significantly shorter in CRCs with NED than in those without, indicating a possible association between NED and early recurrence.
利益披露 Disclosure
Y. Yasuda, None..
K. Murakami, None..
H. Karasawa, None..
W. Kosaka, None..
Y. Akamori, None..
I. Ise, None..
T. Ono, None..
M. Murakami, None..
Y. Sato, None..
G. Yoshimatsu, None..
H. Suzuki, None..
T. Kamei, None..
S. Ohnuma, None..
T. Furukawa, None..
M. Unno, None.