肿瘤细胞异质性与转移：孰因孰果

　　2018年8月1日，施普林格·自然旗下《乳腺癌研究与治疗》正式发表加拿大多伦多大学的研究报告，探讨了肿瘤大小、淋巴结状态与远处转移之间的相关性。该全面和详细的研究报告得出结论，浸润性乳腺癌患者的肿瘤大小、淋巴结状态与远处转移之间的相关性非线性。

　　2018年8月4日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表塞尔维亚贝尔格莱德大学的述评：肿瘤细胞异质性与转移孰因孰果？

　　众所周知，转移过程为多步骤过程，涉及影响肿瘤细胞和周围基质的多种遗传学改变，允许转移向远处部位扩散。肿瘤转移可以通过两种不同模型解释：线性进展模型和平行进展模型，本文根据第一种。我们不能忽视肿瘤细胞释放也可能发生于疾病早期阶段的事实。许多研究证实，约30%～40%的患者在疾病早期可能出现来自循环肿瘤细胞的隐匿转移。相反，临床前动物研究数据表明，不到0.02%的循环肿瘤细胞可以生存并且具有形成转移性病变的能力。很明显，肿瘤细胞的异质性在肿瘤生长期间可以增加。由于缺乏稳定的血液供应和肿瘤进一步坏死，少数细胞可以接近较大肿瘤的血管或淋巴系统。毫无疑问，肿瘤大小是转移和预后的临床和放射学初步预测因素，但是肿瘤细胞遗传学改变异质性和宿主免疫系统状态是乳腺癌患者转移更可预测的因素。详细的原发肿瘤和受累淋巴结或转移性病变组织病理学和免疫组织化学可以提供精准信息，并且确定进一步的诊治方案以及预后。

Breast Cancer Res Treat. 2018 Aug 4.

Heterogeneity of tumor cells and metastases in breast cancer patients: cause or consequence?

Darko Zdravkovic, Dejan Nikolic, Marija Zdravkovic.

University Medical Center, Belgrade, Serbia; University of Belgrade, Belgrade, Serbia.

First of all, we would like to congratulate Sopik and colleague for their article [1] in which they tried to find out a relationship between tumor size, nodal status, and distant metastases. In this very comprehensive and detailed article, the authors concluded that the relationship between tumor size, lymph node status, and distant metastases in patients with invasive breast cancer is not linear. However, we would like to highlight our observation regarding this very important topic.

It is well known that the metastatic process is a multistep process, involving multiple genetic alterations affecting both tumor cells and the surrounding stroma, allowing spreading of metastases at distant sites. Tumor metastasis could be explained by two different models: linear progression model and parallel progression model, and this article is based on the first one. We could not neglect the fact that the release of tumor cells may happen also at early stages of the disease. Many studies confirmed that about 30-40% of patients in early stage of the disease may present occult metastasis derived from circulating tumor cells (CTCs). Contrary, data from preclinical animal studies have shown that less than 0.02% of circulating tumor cells can survive and have the capability to form metastatic lesion [2]. It is obvious that the heterogeneity of tumor cells rises during the tumors growth. We agree with authors that a smaller proportion of cells accessible to the vascular or lymphatic system in larger tumors because of lack of stable blood supply and further tumor necrosis. Undoubtedly that the tumor size is clinically and radiologically initial predictor of metastasis and prognosis, but heterogeneity of tumor cells in terms of genetic alterations and the status of host's immune system is more predictable factor regarding metastases in breast cancer patients. Detailed histopathology and immunohistochemistry of primary tumor and affected lymph nodes or metastatic lesion could give precise information and determine further diagnostic procedures and therapy as well as prognosis [3].

REFERENCES

1. Sopik V, Narod SA. The relationship between tumour size, nodal status and distant metastases: on the origins of breast cancer. Breast Cancer Res Treat. 2018;170(3):647-656.

2. Kimbung S, Loman N, Hedenfalk I. Clinical and molecular complexity of breast cancer metastases. Semin Cancer Biol. 2015;35:85-95.

3. Falck AK, Bendahl PO, Chebil G, et al. Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years' follow-up. Breast Cancer Res Treat. 2013;140(1):93-104.

DOI: 10.1007/s10549-018-4913-9