Matsuura Kazuo, Yamaguchi Yoshiyuki, Osaki Akihiko, Ohara Masahiro, Okita Riki, Emi Akiko, Murakami Shigeru, Arihiro Koji
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Oncol Rep. 2009 Nov;22(5):1181-7. doi: 10.3892/or_00000553.
A number of methods have been established for identifying sentinel nodes (SNs). In the present study, we attempted to clarify the immunological status of SNs with or without micrometastasis in breast cancer patients. SNs were identified by the dye- and gamma probe-guided method. Total RNA was extracted from the SNs, and the expression of T-BET, GATA-3, and FOXP3 were evaluated using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Micrometastasis was identified as microscopically negative but positive by RT-PCR specific for mammaglobin. Of 88 patients, 17 (19.3%) showed positive metastasis in SNs (pN1, 14; pN2, 3). Of the 71 metastasis-negative SNs, 11 showed positive bands on RT-PCR specific for mamma-globin [pN0(mol+)]. There was no significant correlation among clinicopathological features with or without micrometastasis. Immunological parameters were compared among the 60 pN0, 11 pN0(mol+), and 17 pN1-2. Although T-BET expression was higher in pN0(mol+) than pN0, FOXP3 expression was also higher in pN0(mol+) than pN0. In pN1-2, T-BET expression decreased compared with pN0(mol+), but FOXP3 expression did not. On the other hand, GATA-3 expression inversely increased in pN1-2 compared with pN0(mol+). In patients with breast cancer, micrometastasis can stimulate Th1 response in SNs. However, the Treg cell response is also induced at the micrometastasis level and persists during the progression of metastasis in SNs. Then, the shift in the Th1/Th2 balance may preferentially lean toward Th2 responses in pN1-2 SNs and suppress antitumor immune responses. Micrometastasis [pN0(mol+)] is a status immunologically distinguishable from pN0 and pN1-2.
已经建立了多种识别前哨淋巴结（SNs）的方法。在本研究中，我们试图阐明乳腺癌患者中有或无微转移的前哨淋巴结的免疫状态。通过染料和γ探针引导法识别前哨淋巴结。从前哨淋巴结中提取总RNA，并使用定量实时逆转录聚合酶链反应（RT-PCR）评估T-BET、GATA-3和FOXP3的表达。微转移被定义为显微镜下阴性但通过乳腺珠蛋白特异性RT-PCR检测为阳性。88例患者中，17例（19.3%）前哨淋巴结出现阳性转移（pN1，14例；pN2，3例）。在71例转移阴性的前哨淋巴结中，11例在乳腺珠蛋白特异性RT-PCR上显示阳性条带[pN0（mol+）]。有无微转移的临床病理特征之间无显著相关性。比较了60例pN0、11例pN0（mol+）和17例pN1-2患者的免疫参数。虽然pN0（mol+）中T-BET表达高于pN0，但pN0（mol+）中FOXP3表达也高于pN0。在pN1-2中，与pN0（mol+）相比，T-BET表达降低，但FOXP3表达没有降低。另一方面，与pN0（mol+）相比，pN1-2中GATA-3表达反而增加。在乳腺癌患者中，微转移可刺激前哨淋巴结中的Th1反应。然而，Treg细胞反应也在微转移水平被诱导，并在前哨淋巴结转移进展过程中持续存在。然后，Th1/Th2平衡的转变可能在pN1-2前哨淋巴结中优先倾向于Th2反应并抑制抗肿瘤免疫反应。微转移[pN0（mol+）]是一种在免疫上与pN0和pN1-2可区分的状态。
