Department of Surgery, The Brody School of Medicine at East Carolina University, Greenville, NC, USA.
Ann Surg Oncol. 2010 Oct;17 Suppl 3:368-77. doi: 10.1245/s10434-010-1262-2. Epub 2010 Sep 19.
This prospective multicenter sentinel lymph node (SLN) trial investigated whether molecular analysis would improve the detection of SLN metastases and their prognostic value. We report mammaglobin quantitative real-time polymerase chain reaction (qRT-PCR) results and clinical outcome for 547 patients (mean follow-up 7 years).
Breast cancer patients (excluding stage IV disease or palpable nodes) were enrolled from 1996 to 2005 at 16 institutional review board-approved sites. Alternate 2-mm serial sections of each SLN were examined by hematoxylin and eosin staining with or without immunohistochemistry at multiple levels or blinded and assayed by Taqman qRT-PCR according to previously established thresholds.
Mammaglobin remains a highly specific (99%), sensitive (97% primary tumor; 82% N1 SLN) marker for breast cancer. Mammaglobin SLN expression was associated with other prognostic factors, was detected in most patients with distant recurrence (48 of 79; 61%), and was associated with decreased recurrence-free survival (log rank P < 0.0001). Molecular analysis upstaged 13% (52 of 394) node-negative (N0) patients who exhibited a significantly lower distant recurrence-free survival compared to node-negative, PCR-negative patients (80 vs. 91%; P < 0.04). N0 patients with PCR-positive SLN were 3.4 times more likely to experience relapse than PCR-negative patients (odds ratio 3.4; 95% confidence interval 1.6-7.1; P = 0.001). However, molecular staging failed to predict most of the N0 patient recurrences (25 of 34) and was not a statistically significant independent predictor of distant recurrence.
To our knowledge, these data are the first to prospectively compare PCR detection of SLN metastases with long-term outcome in breast cancer patients. Molecular staging of SLN detected clinically significant disease missed by standard pathology. Further refinement and optimization of molecular staging is indicated to improve clinical utility.
本前瞻性多中心前哨淋巴结 (SLN) 试验旨在研究分子分析是否能提高 SLN 转移的检出率及其预后价值。我们报告了 547 例患者（平均随访 7 年）的定量实时聚合酶链反应 (qRT-PCR) 结果和临床结局。
1996 年至 2005 年，在 16 个机构审查委员会批准的地点纳入了乳腺癌患者（不包括 IV 期疾病或可触及的淋巴结）。对每个 SLN 的 2-mm 间隔连续切片，采用苏木精和伊红染色，并在多个水平上进行免疫组化检查，或进行盲法检测，使用 Taqman qRT-PCR 按先前建立的阈值进行检测。
Mammaglobin 仍然是一种高度特异性（99%）、敏感性（原发肿瘤 97%；N1 SLN 82%）的乳腺癌标志物。Mammaglobin SLN 表达与其他预后因素相关，在大多数远处复发患者（48/79；61%）中可检测到，并与无复发生存率降低相关（对数秩 P<0.0001）。分子分析将 13%（52/394）的淋巴结阴性（N0）患者分期上调，这些患者的无远处复发生存率明显低于淋巴结阴性、PCR 阴性患者（80%对 91%；P<0.04）。Mammaglobin SLN 阳性的 N0 患者比 Mammaglobin SLN 阴性患者更有可能复发（优势比 3.4；95%置信区间 1.6-7.1；P=0.001）。然而，分子分期未能预测大多数 N0 患者的复发（34 例中有 25 例），也不是远处复发的统计学上显著独立预测因素。
据我们所知，这些数据首次前瞻性比较了乳腺癌患者 SLN 转移的 PCR 检测与长期结局。SLN 的分子分期检测到了标准病理学遗漏的具有临床意义的疾病。需要进一步改进和优化分子分期，以提高临床实用性。
