Prognostic Significance of the Tumor-Stromal Ratio in Invasive Breast Cancer and a Proposal of a New Ts-TNM Staging System
Prognostic Significance of the Tumor-Stromal Ratio in Invasive Breast Cancer and a Proposal of a New Ts-TNM Staging System
复制标题
浸润性乳腺癌肿瘤间质比的预后意义以及新 Ts-TNM 分期系统的建议
DOI：
10.1155/2020/9050631
复制
发表时间：
2020-04-21
影响因子：
--
通讯作者：
Xiong, Bin
中科院分区：
文献类型：
--
作者：
Xu, Qian;Yuan, Jing-Ping;Xiong, Bin
以往的研究表明，肿瘤间质比（TSR）是几种类型肿瘤的独立预后因素。本研究旨在利用免疫组化（IHC）染色的组织微阵列（TMAs）技术，并将TSR纳入传统的肿瘤-淋巴结-转移（TNM）分期系统，探讨TSR在浸润性乳腺癌中的预后意义。方法制备7个TMAs， 240例患者480例浸润性BC标本，采用免疫组化染色法进行细胞角蛋白（CK）染色。目测肿瘤细胞与间质细胞的比值。将TSR > 1和TSR≤1分别分为高TSR（低基质）组和低TSR（高基质）组，分析TSR在5年无病生存期（5-DFS）的预后价值。建立并评估了一种新的Ts-TNM（肿瘤间质-肿瘤-淋巴结-转移）分期系统。结果CK免疫组化染色能特异性标记肿瘤细胞，造影剂清晰，便于人工评估TSR。高TSR（低间质）占52.5% (n = 126)，低TSR（高间质）占47.5 （n = 114）。Kaplan-Meier分析显示，低TSR组患者的5-DFS较高TSR组患者差（P=0.022）。多变量分析显示，T分期（P=0.014）、N状态（P < 0.001）、组织学分级（P < 0.001）、雌激素受体状态（P=0.015）、TSR （P=0.011）是侵袭性BC患者预后的独立影响因素。结合TSR、肿瘤分期、淋巴结状态、转移分期，建立新的Ts-TNM分期体系。受试者工作特征（ROC）曲线分析显示，Ts-TNM分期系统预测复发的能力不低于TNM分期系统。结论TSR是侵袭性乳腺癌的预后指标之一。包含基质和肿瘤信息的Ts-TNM分期系统可以优化浸润性乳腺癌的风险分层。
Background Previous studies have demonstrated that the tumor-stromal ratio (TSR) was an independent prognostic factor in several types of carcinomas. This study aimed at exploring the prognostic significance of the TSR in invasive breast cancer using immunohistochemistry (IHC)-stained tissue microarrays (TMAs) and integrating the TSR into the traditional tumor-node-metastasis (TNM) staging system. Methods The prepared 7 TMAs containing 240 patients with 480 invasive BC specimens were stained with cytokeratin (CK) by the IHC staining method. The ratio of tumor cells and stromal cells was visually assessed. TSR > 1 and TSR ≤ 1 were categorized as the high TSR (low stroma) and low TSR (high stroma) groups, respectively, and the prognostic value of the TSR at 5-year disease-free survival (5-DFS) was analyzed. A new Ts-TNM (tumor stroma-tumor-node-metastasis) staging system was established and assessed. Results IHC staining of CK could specifically label tumor cells with clear contrast, making it easy to manually assess TSR. High TSR (low stroma) and low TSR (high stroma) were observed in 52.5% (n = 126) and 47.5 (n = 114) of the cases, according to the division of value 1. A Kaplan–Meier analysis showed that patients in the low TSR group had a worse 5-DFS compared with patients in the high TSR group (P=0.022). Multivariable analysis indicated that the T stage (P=0.014), N status (P < 0.001), histological grade (P < 0.001), estrogen receptor status (P=0.015), and TSR (P=0.011) were independent prognostic factors of invasive BC patients. The new Ts-TNM staging system combining TSR, tumor staging, lymph node status, and metastasis staging was established. The receiver operating characteristic (ROC) curve analysis demonstrated that the ability of the Ts-TNM staging system to predict recurrence was not lower than that of the TNM staging system. Conclusions This study confirms that the TSR is a prognostic indicator for invasive breast cancer. The Ts-TNM staging system containing stromal and tumor information may optimize risk stratification for invasive breast cancer.