Institute of Pathology, University Medical Center, Mainz, Germany.
Institute of Pathology, Philipps-University Marburg und University Hospital Marburg, Marburg, Germany.
J Pathol Clin Res. 2024 Sep;10(5):e12394. doi: 10.1002/2056-4538.12394.
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.
抗体药物偶联物（ADCs）针对滋养细胞表面抗原 2（TROP2）已被批准作为晚期三阴性乳腺癌的治疗选择，并且 TROP2 的表达与各种恶性肿瘤的不良预后相关。在结直肠癌（CRC）中，关于其表达频率及其与主要临床病理参数的相关性的综合研究仍然缺乏。我们研究了 TROP2 在 1052 例 CRC 病例的大队列中的表达，并将我们的发现与组织病理学和分子参数、肿瘤分期和患者结局相关联。TROP2 在 214/1052 例 CRC 中（20.3%）呈异质性表达，仅有少数强阳性肿瘤。TROP2 表达与侵袭性组织学表型（例如增加肿瘤芽殖/侵袭性组织病理学亚型）、晚期肿瘤分期、微卫星稳定型肿瘤和 p53 改变显著相关。虽然 TROP2 表达在整个队列的单变量分析中具有预后意义（例如，无病生存率，p<0.001），但在重要的临床病理亚组中存在明显差异（例如，右半与左半 CRC、微卫星稳定与不稳定 CRC、国际抗癌联盟 [UICC] 分期），并且在包括分期和 CRC 组织病理学的多变量分析中失去了意义。总之，TROP2 在 CRC 中表达相当频繁，与侵袭性组织学表型和微卫星稳定型肿瘤相关。未来研究抗 TROP2 ADCs 的临床试验应考虑到观察到的肿瘤内异质性，因为只有一部分表达 TROP2 的 CRC 表现出强烈的阳性。TROP2 的预后意义很复杂，在关键的临床病理亚组中存在显著差异，因此表明 TROP2 是预测患者预后的次优参数。
