Institute of Pathology.
German Cancer Consortium (DKTK), Partner Site Munich.
Am J Surg Pathol. 2019 May;43(5):618-627. doi: 10.1097/PAS.0000000000001230.
Initial treatment planning in esophageal squamous cell carcinoma mainly relies on clinical staging. Recently, a highly prognostic grading system based on the cellular dissociation parameters Tumor Budding and Cell Nest Size has been proposed for resected esophageal squamous cell carcinoma. To probe for the transferability and relevance of this established novel grading system in the pretreatment setting, we evaluated Tumor Budding/Cell Nest Size in pretherapeutic biopsies of either primarily resected (cohort 1, n=80) or neoadjuvantly treated (cohort 2, n=75) esophageal squamous cell carcinoma. Grading data were correlated with clinicopathologic and survival parameters. High Tumor Budding Activity and small Cell Nest Size in pretherapeutic biopsies were strongly associated with shortened overall survival, disease-free survival, and disease-specific survival in both cohorts. A modified histopathologic grading system incorporating both factors termed "Cellular Dissociation Grade" showed excellent prognostic demarcation between well (G1), moderately (G2), and poorly differentiated (G3) carcinomas in both scenarios (overall survival: cohort 1: P<0.001; cohort 2: P=0.009) and was predictive for a high pathologic tumor stage and the presence of nodal metastases in primarily resected patients. Multivariate analyses revealed the Cellular Dissociation Grade to be a predictor of poor outcome in the pretherapeutic setting independent of clinical stage (overall survival, disease-free survival, and disease-specific survival: P<0.001). Hazard ratio for disease-free survival was 3.19 for G2 and 5.66 for G3 carcinomas compared with G1 neoplasms. Our data not only prove the transferability of histopathologic grading based on Tumor Budding/Cell Nest Size to biopsy specimens in esophageal squamous cell carcinoma, but also demonstrate that the Cellular Dissociation Grade is a strong outcome predictor in this entity even in the pretreatment scenario. Therefore, we believe that this novel type of grading has the ability to serve as a powerful histology-based pretherapeutic biomarker, that might supplement clinical staging for choosing the most suitable therapy decision.
在食管鳞状细胞癌的初始治疗计划中，主要依赖于临床分期。最近，提出了一种基于肿瘤芽殖和细胞巢大小的细胞分离参数的高度预后分级系统，用于切除的食管鳞状细胞癌。为了探讨该新型分级系统在治疗前评估中的可转移性和相关性，我们评估了经原发切除（队列 1，n=80）或新辅助治疗（队列 2，n=75）的食管鳞状细胞癌的治疗前活检中的肿瘤芽殖/细胞巢大小。分级数据与临床病理和生存参数相关。在两个队列中，治疗前活检中高肿瘤芽殖活性和小细胞巢大小与总生存期、无病生存期和疾病特异性生存期缩短密切相关。在两种情况下，包含这两个因素的改良组织病理学分级系统“细胞分离分级”在良好（G1）、中度（G2）和低分化（G3）癌之间显示出极好的预后区分（总生存期：队列 1：P<0.001；队列 2：P=0.009），并且可以预测原发切除患者的高病理肿瘤分期和淋巴结转移的存在。多变量分析显示，在治疗前环境中，细胞分离分级是临床分期之外预测不良结局的一个指标（总生存期、无病生存期和疾病特异性生存期：P<0.001）。G2 和 G3 癌的疾病无进展生存期危险比分别为 G1 肿瘤的 3.19 和 5.66。我们的数据不仅证明了基于肿瘤芽殖/细胞巢大小的组织病理学分级在食管鳞状细胞癌活检标本中的可转移性，而且还证明了在该实体中，细胞分离分级甚至在治疗前环境中也是一个强大的预后预测因子。因此，我们认为这种新型分级具有作为一种强大的基于组织学的治疗前生物标志物的能力，可能补充临床分期，为选择最合适的治疗决策提供依据。
