结直肠癌中的 TROP2:与组织病理学、分子表型和患者预后的关系。

IF 3.4 2区 医学 Q1 PATHOLOGY
Sebastian Foersch, Maxime Schmitt, Anne-Sophie Litmeyer, Markus Tschurtschenthaler, Thomas Gress, Detlef K Bartsch, Nicole Pfarr, Katja Steiger, Carsten Denkert, Moritz Jesinghaus
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引用次数: 0

摘要

针对滋养层细胞表面抗原 2(TROP2)的抗体药物共轭物(ADCs)已被批准作为晚期三阴性乳腺癌的治疗选择,TROP2 的表达与各种恶性肿瘤的不良预后有关。在结直肠癌(CRC)中,目前仍缺乏关于其表达频率及其与主要临床病理参数相关的预后影响的全面研究。我们研究了 1,052 例 CRC 病例中 TROP2 的表达情况,并将研究结果与组织病理学和分子参数、肿瘤分期以及患者预后相关联。在 214/1,052 例 CRC(20.3%)中,TROP2 呈异质性表达,仅有部分肿瘤呈强阳性。TROP2的表达与侵袭性组织学表型(如肿瘤萌芽增加/侵袭性组织病理学亚型)、肿瘤晚期、微卫星稳定肿瘤和p53改变密切相关。虽然在对整个队列进行的单变量分析中,TROP2的表达对预后有影响(如无病生存期,p
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TROP2 in colorectal carcinoma: associations with histopathology, molecular phenotype, and patient prognosis

TROP2 in colorectal carcinoma: associations with histopathology, molecular phenotype, and patient prognosis

Antibody–drug conjugates (ADCs) directed to trophoblast cell surface antigen 2 (TROP2) have gained approval as a therapeutic option for advanced triple-negative breast cancer, and TROP2 expression has been linked to unfavourable outcomes in various malignancies. In colorectal carcinoma (CRC), there is still a lack of comprehensive studies on its expression frequency and its prognostic implications in relation to the main clinicopathological parameters. We examined the expression of TROP2 in a large cohort of 1,052 CRC cases and correlated our findings with histopathological and molecular parameters, tumour stage, and patient outcomes. TROP2 was heterogeneously expressed in 214/1,052 CRCs (20.3%), with only a fraction of strongly positive tumours. TROP2 expression significantly correlated with an invasive histological phenotype (e.g. increased tumour budding/aggressive histopathological subtypes), advanced tumour stage, microsatellite stable tumours, and p53 alterations. While TROP2 expression was prognostic in univariable analyses of the overall cohort (e.g. for disease-free survival, p < 0.001), it exhibited distinct variations among important clinicopathological subgroups (e.g. right- versus left-sided CRC, microsatellite stable versus unstable CRC, Union for International Cancer Control [UICC] stages) and lost its significance in multivariable analyses that included stage and CRC histopathology. In summary, TROP2 is quite frequently expressed in CRC and associated with an aggressive histopathological phenotype and microsatellite stable tumours. Future clinical trials investigating anti-TROP2 ADCs should acknowledge the observed intratumoural heterogeneity, given that only a subset of TROP2-expressing CRC show strong positivity. The prognostic implications of TROP2 are complex and show substantial variations across crucial clinicopathological subgroups, thus indicating that TROP2 is a suboptimal parameter to predict patient prognosis.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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