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犬浸润性尿路上皮癌中罕见组织学亚型的频率及特征

Frequency and Characterization of Rare Histologic Subtypes in Canine Invasive Urothelial Carcinoma.

作者信息

Corbett Megan P, Elbadawy Mohamed, Woodward Andrew P, Cheville John C, Wickham Hannah, Nicholson Hannah, Catucci Michael, Melvin Bryan J, Ahmed Basant, Zdyrski Christopher, Oliveira Lilian J, Howerth Elizabeth W, Pawlak Aleksandra, Fasina Olufemi, Mochel Jonathan P, Allenspach Karin

机构信息

Precision One Health Initiative, Department of Pathology, University of Georgia College of Veterinary Medicine, 30602 Athens, GA USA.

Department of Pharmacology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt.

出版信息

bioRxiv. 2025 May 14:2025.05.13.651218. doi: 10.1101/2025.05.13.651218.

Abstract

UNLABELLED

The histologic and molecular heterogeneity of human muscle-invasive bladder cancer (MIBC) is a major contributor to poor treatment outcomes. While most cases of MIBC are diagnosed as conventional urothelial carcinoma (UC), there is growing recognition of histologic subtypes and divergent differentiation within conventional UC. This is clinically significant, as some require modification of therapy and some are associated with more aggressive behavior. Spontaneously occurring UC in dogs has been shown to exhibit histologic and molecular features that closely resemble those of human MIBC. In this study, we evaluated 31 canine UC tumor samples for histologic subtypes and divergent differentiation. Slides were reviewed by a human uropathologist and three board-certified veterinary pathologists and assessed for expression of uroplakin III and E-cadherin. All tumors were classified as high-grade UC. Fifteen cases were identified as conventional UC. Among the remainder, eight displayed glandular differentiation, four were classified as sarcomatoid UC, two showed squamous differentiation, and one case each was classified as large nested and tubular and microcystic subtypes. In summary, this study found a higher frequency of certain histologic subtypes and divergent differentiation in canine UC-particularly sarcomatoid UC and UC with glandular differentiation-compared to previous reports in both canine UC and human MIBC.

CONCLUSION

The relatively high prevalence of the sarcomatoid UC subtype in dogs observed in this study suggests that canine UC may serve as a valuable translational model for evaluating novel therapeutic agents, particularly for this rare and aggressive variant in humans.

摘要

未标注

人类肌层浸润性膀胱癌(MIBC)的组织学和分子异质性是导致治疗效果不佳的主要因素。虽然大多数MIBC病例被诊断为传统尿路上皮癌(UC),但人们越来越认识到传统UC内的组织学亚型和分化差异。这在临床上具有重要意义,因为有些病例需要调整治疗方案,有些则与更具侵袭性的行为相关。已证明犬自发性UC表现出与人类MIBC非常相似的组织学和分子特征。在本研究中,我们评估了31例犬UC肿瘤样本的组织学亚型和分化差异。玻片由一名人类泌尿病理学家和三名获得委员会认证的兽医病理学家进行复查,并评估尿路上皮蛋白III和E-钙黏蛋白的表达。所有肿瘤均被分类为高级别UC。15例被鉴定为传统UC。其余病例中,8例显示腺性分化,4例被分类为肉瘤样UC,2例显示鳞状分化,1例分别被分类为大巢状和管状以及微囊性亚型。总之,本研究发现,与之前犬UC和人类MIBC的报道相比,犬UC中某些组织学亚型和分化差异的频率更高,尤其是肉瘤样UC和腺性分化的UC。

结论

本研究中观察到的犬肉瘤样UC亚型相对较高的患病率表明,犬UC可能作为一种有价值的转化模型,用于评估新型治疗药物,特别是针对人类这种罕见且侵袭性强的变体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1926/12132475/0e350f6765d2/nihpp-2025.05.13.651218v1-f0001.jpg

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