Unveiling the Prognostic Role of Synaptophysin in Conventional Colorectal Carcinomas.

IF 3.2 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Neuroendocrinology Pub Date : 2025-05-05 DOI:10.1159/000545979

Giovanna Sabella, Giovanni Centonze, Vincenzo Lagano, Andrea Scardino, Filiberto Belli, Giovanna Garzone, Carlotta Pardo, Daniela Galbiati, Sara Pusceddu, Alessandro Mangogna, Valentina Angerilli, Matteo Fassan, Andrea Vingiani, Luca Agnelli, Giancarlo Pruneri, Stefania Gobba, Silvia Uccella, Stefano La Rosa, Fausto Sessa, Carlo Capella, Massimo Milione

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引用次数: 0

Abstract

Introduction: Although neuroendocrine differentiation in colorectal carcinomas (CRCs) has been extensively reported, the biological behavior of adenocarcinomas expressing synaptophysin (Syn) but lacking typical neuroendocrine morphology remains unclear.

Methods: We tested 663 conventional CRCs with non-neuroendocrine morphology for Syn expression and correlated the results with clinicopathological and molecular characteristics as well as patient survival (overall survival [OS] and disease-free survival [DFS]). The survival characteristics of Syn expression group were compared to those of conventional CRCs and subsequently to those of 14 MiNENs.

Results: Syn immunohistochemical expression ≥30% was confirmed in 27 (4.1%) patients and correlated with right colon site, grade 2, marked intratumoral lymphocyte infiltrate and BRAF p.V600E mutation. At univariate analysis variables associated with poor OS were 10-year increase in age (p=0.001), stage IIII-IV (p=0.001), Syn ≥30% (p=0.001), infiltrative growth (p=0.04) and residual tumor R1-2 (p=0.03). At multivariable analysis, Syn expression in ≥30% of gland-forming tumor cells emerged as an independent negative prognostic factor for both OS and DFS. Moreover 10-year increase in age, stage III-IV and Syn ≥30% (p<0.001) were associated with poor OS and marked peritumoral lymphocyte infiltrate with longer OS (p=0.02). Comparable results were obtained according to DFS; in addition, right colon site (p=0.04) was associated with longer DFS while KRAS mutation (p=0.04) was associated with poor DFS at univariate analysis. MiNEN patients showed a shorter DFS than all conventional adenocarcinomas with or without Syn expression in univariate analyses (p<0,001).

Conclusions: Among conventional CRCs, we provided evidence that Syn expression is associated with worse OS and DFS and contributes to predicting clinical outcome. Future studies should explore the molecular mechanisms underlying the acquisition of the neuroendocrine phenotype to identify new targeted treatment strategies.

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揭示突触素在常规结直肠癌中的预后作用。

虽然大肠癌（crc）的神经内分泌分化已被广泛报道，但表达synaptophysin （Syn）但缺乏典型神经内分泌形态的腺癌的生物学行为尚不清楚。方法：我们检测了663例非神经内分泌形态的常规crc的Syn表达，并将结果与临床病理和分子特征以及患者生存期（总生存期[OS]和无病生存期[DFS]）相关联。将Syn表达组的生存特征与常规crc进行比较，随后与14例MiNENs进行比较。结果：27例（4.1%）患者证实Syn免疫组化表达≥30%，与右结肠部位2级、瘤内淋巴细胞浸润明显、BRAF p.V600E突变相关。在单因素分析中，与不良OS相关的变量为年龄增加10年（p=0.001）、iii - iv期（p=0.001）、Syn≥30% （p=0.001）、浸润性生长（p=0.04）和残留肿瘤R1-2 （p=0.03）。在多变量分析中，Syn在≥30%的腺体形成肿瘤细胞中的表达成为OS和DFS的独立负面预后因素。此外，年龄增加10年，III-IV期和Syn≥30%(结论：在常规crc中，我们提供的证据表明Syn表达与更差的OS和DFS相关，并有助于预测临床结局。未来的研究应探索神经内分泌表型获得的分子机制，以确定新的靶向治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroendocrinology 医学-内分泌学与代谢

CiteScore

8.30

自引率

2.40%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.