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预测前哨淋巴结阳性乳腺癌患者非前哨淋巴结转移的临床病理参数和生物学标志物。

Clinicopathological parameters and biological markers predicting non-sentinel node metastasis in sentinel node-positive breast cancer patients.

机构信息

Research Institute and Hospital, National Cancer Center, Gyeonggi-do, Republic of Korea.

出版信息

Oncol Rep. 2011 Apr;25(4):1063-71. doi: 10.3892/or.2011.1157. Epub 2011 Jan 21.

DOI:10.3892/or.2011.1157
PMID:21258771
Abstract

The value of complete axillary lymph node dissection (ALND) has been questioned in invasive breast cancer (IBC) patients with positive sentinel lymph nodes (SLNs) who have no non-sentinel lymph node (NSLN) metastases. Because biological markers have not been systematically studied in this setting, we sought to identify clinicopathological characteristics and biological markers for predicting NSLN metastases in SLN-positive IBC patients. Two hundred and five IBC patients who had at least one positive SLN and received SLN biopsy and ALND were included in our study. We examined the clinicopathological characteristics of their primary tumors, SLNs and NSLNs. We also evaluated the biological markers of the primary tumors by tissue microarray and immunohistochemistry. Of the 205 patients with SLN metastases, 89 patients (43.4%) had additional metastases in NSLNs. The following factors were found to be associated with NSLN metastases: peritumoral lymphovascular invasion (p=0.01), two or more metastatic SLNs (p<0.01), SLN metastasis >2.0 mm (p<0.01) and extra-nodal extension (p<0.01). Primary tumors >2.0 cm showed more NSLN metastases, but the association was statistically insignificant (p=0.08). In contrast, NSLN metastases were not associated with histologic grade, histologic type, presence of extensive intraductal component, presence of high grade ductal carcinoma in situ and number of harvested SLNs. Biological markers such as E-cadherin, CD44, cyclin D1, p21, ER, PR, c-erbB2, p53, Ki-67, luminal (CK7, CK18, CK19) and basal (CK5, p63) markers were not useful predictors of NSLN metastasis in IBC patients with SLN metastases. Multivariate analysis revealed that SLN metastasis >2.0 mm (p=0.01), two or more metastatic SLNs (p=0.03) and extranodal extension (p<0.01) were independent predictors of NSLN metastasis. For the prediction of NSLN metastasis in IBC patients with SLN metastases, light microscopic evaluation of the number, size and extranodal extension of metastatic SLNs by hematoxylin and eosin staining appeared to be critical. However, the biological markers of primary tumor characterized by immunohistochemical staining, such as luminal and basal markers, hormone receptors, E-cadherin, CD44, cyclin D1, p21, c-erb-B2, p53 and Ki-67, did not appear to be helpful predictors.

摘要

前哨淋巴结活检阳性且无非前哨淋巴结转移的浸润性乳腺癌患者中,完整腋窝淋巴结清扫术的价值受到质疑。由于在这种情况下尚未系统地研究生物学标志物,因此我们试图确定预测前哨淋巴结活检阳性的浸润性乳腺癌患者非前哨淋巴结转移的临床病理特征和生物学标志物。我们纳入了 205 例至少有 1 个前哨淋巴结阳性且接受前哨淋巴结活检和腋窝淋巴结清扫术的浸润性乳腺癌患者,对其原发肿瘤、前哨淋巴结和非前哨淋巴结的临床病理特征进行了分析。我们还通过组织微阵列和免疫组织化学评估了原发肿瘤的生物学标志物。在 205 例前哨淋巴结转移的患者中,89 例(43.4%)非前哨淋巴结有额外转移。结果发现,以下因素与非前哨淋巴结转移相关:肿瘤周围淋巴管侵犯(p=0.01)、两个或更多转移的前哨淋巴结(p<0.01)、前哨淋巴结转移>2.0mm(p<0.01)和淋巴结外扩展(p<0.01)。原发肿瘤>2.0cm 显示出更多的非前哨淋巴结转移,但相关性无统计学意义(p=0.08)。相反,非前哨淋巴结转移与组织学分级、组织学类型、广泛的导管内成分、高级别导管原位癌和前哨淋巴结的数量无关。生物学标志物如 E-钙黏蛋白、CD44、细胞周期蛋白 D1、p21、ER、PR、c-erbB2、p53、Ki-67、腔面标志物(CK7、CK18、CK19)和基底标志物(CK5、p63)不能预测前哨淋巴结转移的浸润性乳腺癌患者的非前哨淋巴结转移。多因素分析显示,前哨淋巴结转移>2.0mm(p=0.01)、两个或更多转移的前哨淋巴结(p=0.03)和淋巴结外扩展(p<0.01)是非前哨淋巴结转移的独立预测因子。对于前哨淋巴结转移的浸润性乳腺癌患者,苏木精-伊红染色对转移前哨淋巴结的数量、大小和淋巴结外扩展的光镜评估似乎至关重要。然而,通过免疫组织化学染色特征化的原发肿瘤的生物学标志物,如腔面和基底标志物、激素受体、E-钙黏蛋白、CD44、细胞周期蛋白 D1、p21、c-erb-B2、p53 和 Ki-67,似乎不是有帮助的预测因子。

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