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胃非典型增生和发育异常中MUC5AC、MUC6、P53和Ki67独特的免疫组化特征

Unique immunohistochemical profiles of MUC5AC, MUC6, P53, and Ki67 in gastric atypical hyperplasia and dysplasia.

作者信息

Miao Lanfang, Sun Yuanyuan, Guo Mei, Yang Haijun, Du Xianjuan, Li Junkuo, Shen Jingwei, Wang Xiaomin, Lei Ruixue

机构信息

Department of Pathology, Anyang Tumor Hospital/The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology Anyang 455000, Henan, China.

Department of Radiotherapy, Anyang Tumor Hospital/The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology Anyang 455000, Henan, China.

出版信息

Int J Clin Exp Pathol. 2024 Mar 15;17(3):63-71. doi: 10.62347/JVIX8887. eCollection 2024.

Abstract

OBJECTIVES

Differentiating gastric atypical hyperplasia (AH) from dysplasia, including low-grade dysplasia (LGD) and high-grade dysplasia (HGD), poses significant challenges in small biopsies and specimens with technical artifacts. This study aims to establish objective diagnostic criteria for these conditions through combined morphologic and immunohistochemical (IHC) analyses.

METHODS

Between January 2018 and September 2020, a total of 123 gastric mucosa biopsy specimens were collected at Anyang Tumor Hospital. According to the WHO Classification of Digestive System Tumors (5 edition), specimens were categorized into three groups: AH (n=48), LGD (n=30), and HGD (n=45). Morphologic characteristics were assessed, and IHC staining for MUC5AC, MUC6, MUC2, CD10, P53, and Ki67 was performed, followed by statistical analysis.

RESULTS

Histologically, AH was predominantly marked by a pronounced inflammatory background (60.42%), intestinal metaplasia (64.58%), indistinct boundaries (83.33%), and a distinct maturation gradient (97.72%). AH nuclei were typically circular (97.92%), with a high nucleus-to-cytoplasm ratio (64.58%), prominent nucleoli (47.92%), and preserved polarity (89.58%). In contrast, LGD and HGD typically exhibited well-defined boundaries with an absent maturation gradient. LGD nuclei were rod-shaped (96.67%), with a low nucleus-to-cytoplasm ratio (96.67%) and preserved polarity (100%), whereas HGD demonstrated a loss of cellular polarity (77.78%). IHC findings revealed a consistent maturation gradient in AH, with polarized MUC5AC and MUC6 expression, significantly reduced in LGD (86.67%), and absent in HGD. P53 expression in HGD showed a predominant 'mutation-type pattern' (66.67%), contrasting with 'wild-type pattern' expression in AH and LGD (100%, 93.33%). Ki67 expression patterns varied from a 'pit neck pattern' in AH (95.83%) to a 'polarity pattern' in LGD (76.67%) and a 'diffuse pattern' in HGD (57.78%). The expression patterns of MUC5AC, MUC6, CD10, P53, and Ki67 varied significantly across the three groups (<0.001).

CONCLUSIONS

The integration of histomorphological features and expression profiles of MUC5AC, MUC6, P53, and Ki67 is instrumental in diagnosing gastric atypical hyperplasia and dysplasia.

摘要

目的

在小活检标本及存在技术假象的标本中,鉴别胃非典型增生(AH)与发育异常,包括低级别发育异常(LGD)和高级别发育异常(HGD),面临重大挑战。本研究旨在通过形态学和免疫组织化学(IHC)联合分析,为这些病症建立客观的诊断标准。

方法

2018年1月至2020年9月期间,安阳市肿瘤医院共收集了123例胃黏膜活检标本。根据世界卫生组织消化系统肿瘤分类(第5版),标本分为三组:AH(n = 48)、LGD(n = 30)和HGD(n = 45)。评估形态学特征,并进行MUC5AC、MUC6、MUC2、CD10、P53和Ki67的免疫组织化学染色,随后进行统计分析。

结果

组织学上,AH主要表现为明显的炎症背景(60.42%)、肠化生(64.58%)、边界不清(83.33%)和明显的成熟梯度(97.72%)。AH细胞核通常呈圆形(97.92%),核质比高(64.58%),核仁明显(47.92%),极性保留(89.58%)。相比之下,LGD和HGD通常边界清晰,无成熟梯度。LGD细胞核呈杆状(96.67%),核质比低(96.67%),极性保留(100%),而HGD显示细胞极性丧失(77.78%)。免疫组织化学结果显示,AH中存在一致的成熟梯度,MUC5AC和MUC6表达呈极性,在LGD中显著降低(86.67%),在HGD中缺失。HGD中P53表达以“突变型模式”为主(66.67%),与AH和LGD中的“野生型模式”表达形成对比(100%,93.33%)。Ki67表达模式从AH中的“腺颈部模式”(95.83%)到LGD中的“极性模式”(76.67%)再到HGD中的“弥漫模式”(57.78%)各不相同。MUC5AC、MUC6、CD10、P53和Ki67的表达模式在三组之间差异显著(<0.001)。

结论

MUC5AC、MUC6、P53和Ki67的组织形态学特征与表达谱的整合有助于诊断胃非典型增生和发育异常。

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