Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.
J Pathol. 2022 Jul;257(4):561-574. doi: 10.1002/path.5902. Epub 2022 May 3.
Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post-surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri-tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter-patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri-tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri-tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
全球每七个女性一生中就有一个会受到乳腺癌的影响。广泛的乳房 X 光筛查计划和教育活动使得疾病能够得到早期发现，通常是在无症状阶段。目前的治疗和复发监测实践主要基于病理评估，但也可以包括基因组评估，两者都侧重于原发性肿瘤。尽管乳腺癌是研究最多的癌症之一，但患者在手术后 10 年内仍有高达 15%的复发率。局部复发最初归因于肿瘤细胞在手术切缘之外的组织学正常（HN）组织中污染，但技术的进步允许鉴定出存在于肿瘤周围组织本身中的独特异常。一种主要的理论是肿瘤发生场理论来解释这一现象。根据这一假说，肿瘤是由分子改变的细胞群产生的，这些细胞群为恶性进化创造了一个允许的环境，这种进化可能发生也可能不发生形态变化。传统的组织病理学范式表明，分子改变反映在组织表型中。然而，正常乳腺组织的个体间变异性谱可能会使人们在常规诊断中难以识别肿瘤化的领域。在这篇综述中，我们探讨了肿瘤发生场的概念，重点是 HN 肿瘤周围组织：我们介绍了这些组织中肿瘤发生场的病理学和分子特征，并讨论了如何使用肿瘤周围组织来影响研究。我们的观察表明，病理和分子评估可以协同使用，以评估风险并指导患者的治疗管理。© 2022 作者。《病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学学会出版。
