Ohlsson-Wilhelm B M, Wang G
Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Eur J Histochem. 1994;38 Suppl 1:77-82.
Needle-directed excisional breast biopsy (NDBB) is performed on many women having suspicious mammograms. Only a small subset of these women (approximately 20%) will be found to have breast cancer. The goal of this study was to test the hypothesis that presence (or absence) of circulating lymphocytes able to kill cultured breast cancer-derived cell lines would discriminate the subset of women with early forms of breast cancer from those with benign breast disease. The immune status of over 200 women undergoing NDBB was ascertained at the time of biopsy from a peripheral blood sample. Use of a standard surface immunophenotyping panel able to discriminate a variety of both natural killer cells and cytotoxic T lymphocytes revealed no significant differences when compared to a group of healthy volunteers or to the normal ranges established for our laboratory. Functional assays (cytotoxicity studies) were performed in a blinded fashion on peripheral blood lymphocytes from a subset (N = 31) of these women using a panel of target cell lines. Target cells included the NK sensitive K562; the NK resistant Daudi; and two breast cancer-derived cell lines, the hormone sensitive MCF7 and MDA-MB-435 which has been shown to metastasize in immunocompromised mice. No differences were apparent among the groups with respect to ability to kill either K562 or Daudi. All individuals undergoing NDBB had an enhanced ability to kill the breast cancer-derived cell lines compared to healthy donors. Individuals with breast cancer killed, on average, twice as many MCF7 cells as than did individuals with benign breast disease whereas both groups killed approximately three times as many MDA-MB-435 cells as did healthy donors. Further, a higher proportion of the women undergoing NDBB (2-3x) had relatively high cytotoxic ability directed against the breast cancer-derived lines than was found among healthy donors. These data expand earlier observations (Hamilton et al., 1988) that women with stage I breast cancer had elevated ability to kill MCF7 to include a substantial subset of all women with suspicious mammograms.
许多乳房X光检查结果可疑的女性会接受针引导下的乳房切除活检（NDBB）。这些女性中只有一小部分（约20%）会被查出患有乳腺癌。本研究的目的是检验这样一个假设，即能够杀死培养的乳腺癌衍生细胞系的循环淋巴细胞的存在（或不存在），可以区分患有早期乳腺癌的女性子集和患有良性乳腺疾病的女性。在活检时，从200多名接受NDBB的女性的外周血样本中确定其免疫状态。使用能够区分多种自然杀伤细胞和细胞毒性T淋巴细胞的标准表面免疫表型分析面板，与一组健康志愿者或我们实验室确定的正常范围相比，没有发现显著差异。对这些女性的一个子集（N = 31）的外周血淋巴细胞进行了盲法功能测定（细胞毒性研究），使用一组靶细胞系。靶细胞包括NK敏感的K562；NK抗性的Daudi；以及两种乳腺癌衍生细胞系，激素敏感的MCF7和已被证明在免疫受损小鼠中会转移的MDA-MB-435。在杀死K562或Daudi的能力方面，各组之间没有明显差异。与健康供体相比，所有接受NDBB的个体杀死乳腺癌衍生细胞系的能力都有所增强。患有乳腺癌的个体平均杀死的MCF7细胞数量是患有良性乳腺疾病个体的两倍，而两组杀死的MDA-MB-435细胞数量均约为健康供体的三倍。此外，接受NDBB的女性中具有针对乳腺癌衍生细胞系的相对较高细胞毒性能力的比例（2 - 3倍）高于健康供体。这些数据扩展了早期的观察结果（Hamilton等人，1988年），即I期乳腺癌女性杀死MCF7的能力有所提高，这一结果涵盖了所有乳房X光检查结果可疑的女性中的相当一部分。
