Thor A, Viglione M J, Ohuchi N, Simpson J, Steis R, Cousar J, Lippman M, Kufe D W, Schlom J
Laboratory of Tumor Immunology and Biology, NCI, Bethesda, MD 20892.
Breast Cancer Res Treat. 1988 May;11(2):133-45. doi: 10.1007/BF01805837.
Twenty percent (n = 6) of Stage III or IV breast cancer patients (n = 30) had bone marrow metastases detected in bilateral bone marrow biopsy/aspiration preparations using standard histologic preparations. Each metastasis was also detected by four separate monoclonal antibodies (MAbs) which recognize breast carcinoma associated antigens (DF3, anti-EMA, HMFG-2, and CAM5.2). These MAbs were then utilized to stain other bone marrow preparations (n = 81) to determine their utility for the detection of micrometastatic breast carcinoma. MAbs HMFG-2, anti-EMA, and DF3 were each strongly reactive with bone marrows containing histologically-evident metastatic breast carcinoma (18/18). These anti-epithelial membrane antigen MAbs, however, were also reactive with rare plasma cells and immature cells (as well as cell clusters) in some of the control bone marrow samples tested, including those from normal patients and patients with hematologic disorders. They also reacted with some of the preparations from patients with leukemia and lymphoma, and with uninvolved marrows from patients with non-epithelial malignancies. The anti-keratin MAb CAM5.2, in contrast, reacted with 83% (15/18) breast cancer metastases and failed to stain any cells in the various categories of control marrow preparations. These data suggested that MAb CAM5.2 might be utilized to immunohistochemically differentiate micrometastatic breast carcinoma from immature myeloid or erythroid elements. Each MAb was then reacted with histologically uninvolved marrow preparations from the remaining 24 of 30 breast cancer patients in an attempt to identify occult breast carcinoma metastases. While MAbs HMFG-2, DF3, and anti-EMA demonstrated reactive cells in some of these marrows, this reactivity was similar to that seen with control preparations. MAb CAM5.2, in contrast, was negative with all specimens. These data suggest that MAb CAM5.2 may be a useful immunologic probe for the detection and confirmation of metastatic breast carcinoma in bone marrow, while more caution must be employed in the interpretation of results obtained using MAbs anti-EMA, DF3, and HMFG-2.
在30例III期或IV期乳腺癌患者中，20%（n = 6）的患者通过标准组织学制片在双侧骨髓活检/穿刺标本中检测到骨髓转移。每个转移灶也可被识别乳腺癌相关抗原的4种不同单克隆抗体（MAb，即DF3、抗上皮膜抗原抗体、HMFG - 2和CAM5.2）检测到。然后利用这些单克隆抗体对其他骨髓标本（n = 81）进行染色，以确定它们在检测微小转移乳腺癌方面的效用。MAb HMFG - 2、抗上皮膜抗原抗体和DF3与含有组织学上明显的转移性乳腺癌的骨髓均呈强反应（18/18）。然而，这些抗上皮膜抗原单克隆抗体在一些检测的对照骨髓样本中，包括来自正常患者和血液系统疾病患者的样本中，也与罕见的浆细胞和未成熟细胞（以及细胞簇）发生反应。它们也与白血病和淋巴瘤患者的一些标本以及非上皮性恶性肿瘤患者的未受累骨髓发生反应。相比之下，抗角蛋白单克隆抗体CAM5.2与83%（15/18）的乳腺癌转移灶发生反应，且在各类对照骨髓标本中未对任何细胞进行染色。这些数据表明，单克隆抗体CAM5.2可用于免疫组织化学鉴别微小转移乳腺癌与未成熟的髓系或红系细胞成分。然后让每种单克隆抗体与30例乳腺癌患者中其余24例组织学上未受累的骨髓标本反应，试图识别隐匿性乳腺癌转移灶。虽然MAb HMFG - 2、DF3和抗上皮膜抗原抗体在其中一些骨髓中显示有反应性细胞，但这种反应性与对照标本所见相似。相比之下，单克隆抗体CAM5.2对所有标本均呈阴性。这些数据表明，单克隆抗体CAM5.2可能是检测和确认骨髓中转移性乳腺癌的一种有用的免疫探针，而在解释使用抗上皮膜抗原抗体、DF3和HMFG - 2单克隆抗体获得的结果时必须更加谨慎。
