Introduction: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists’ interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. Methods: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. Results: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250–500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels > 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. Conclusions: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (<20 min) and can be performed without special equipment by non-specialized personnel, suggesting future point-of-care testing for BIA-ALCL may be feasible.
引言：乳房植入物相关间变性大细胞淋巴瘤（BIA-ALCL）通常表现为种植体周围积液（血清肿）。CD30（TNFRSF8）是肿瘤细胞的稳定标志物，但也可在良性血清肿中被活化的淋巴细胞表达。目前BIA-ALCL的诊断包括细胞学检查以及通过免疫组化或流式细胞术检测CD30，但这些检测需要专业设备和病理医师判读。我们假设CD30侧向层析检测法（LFA）可为可溶性CD30提供一种成本较低的快速检测方法，最终可能由非专业人员用于BIA-ALCL的即时诊断。 方法：我们对15例病理确诊的BIA-ALCL患者和10例良性血清肿患者进行了CD30 LFA检测和酶联免疫吸附试验（ELISA）。为确定LFA检测CD30的动态范围，我们在通用缓冲液中加入七种不同浓度（125 pg/mL至10,000 pg/mL）的重组CD30蛋白。随后对10例病理确诊的BIA-ALCL患者和10例良性血清肿患者的冷冻保存血清肿样本进行CD30 LFA检测。 结果：加入通用缓冲液的重组CD30蛋白在浓度高于1000 pg/mL时产生清晰检测线，在250–500 pg/mL时产生微弱检测线。LFA检测显示：所有未稀释的BIA-ALCL血清肿样本均呈阳性检测线；10例恶性血清肿样本在1:10稀释后有8例呈阳性；10例良性血清肿样本中有3例未稀释时呈阳性，但所有样本在1:10稀释后均呈阴性。未稀释样本的CD30 LFA检测对BIA-ALCL的敏感性为100.00%，特异性为70.00%，阳性预测值为76.92%，阴性预测值为100.00%。当样本稀释1:10时，敏感性降至80.00%，但特异性和阳性预测值均提高至100.00%，而阴性预测值降至88.33%。ELISA检测显示：6例良性血清肿的CD30浓度均低于1200 pg/mL；7例BIA-ALCL血清肿的CD30水平均>2300 pg/mL（除1例外，其余均通过1:10或1:50稀释计算得出）。 结论：CD30 ELISA和LFA均可区分BIA-ALCL血清肿与良性血清肿，但LFA耗时更短（<20分钟）且无需专业设备，可由非专业人员操作，提示未来开展BIA-ALCL即时检测具有可行性。
CD30 Lateral Flow and Enzyme-Linked Immunosorbent Assays for Detection of BIA-ALCL: A Pilot Study
肿瘤(癌症)患者之家