Shivers S C, Wang X, Li W, Joseph E, Messina J, Glass L F, DeConti R, Cruse C W, Berman C, Fenske N A, Lyman G H, Reintgen D S
Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Department of Surgery, University of South Florida, Tampa 33612, USA.
JAMA. 1998 Oct 28;280(16):1410-5. doi: 10.1001/jama.280.16.1410.
For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases.
To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma.
A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months.
A major university-based melanoma referral center at a National Cancer Institute-designated cancer center.
A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases.
Melanoma recurrence and overall survival.
Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival.
The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.
对于大多数实体瘤而言，区域淋巴结的转移状态是复发和生存的最强预测指标。然而，淋巴结的常规病理检查可能会低估黑色素瘤发生淋巴结转移的患者数量。
确定一种用于检测隐匿性淋巴结转移的高灵敏度分子检测方法对黑色素瘤患者分期的临床意义。
一项对连续患者进行的前瞻性队列研究，对114例临床I期和II期黑色素瘤患者进行淋巴绘图和前哨淋巴结（SLN）活检。将SLN切成两半，每个标本的一半送去进行常规病理检查。另一半送去使用逆转录酶-聚合酶链反应（RT-PCR）检测酪氨酸酶信使核糖核酸，以作为黑色素瘤细胞存在的标志物，用于亚微观转移的分子检测。患者平均随访28个月。
一所国立癌症研究所指定癌症中心的主要大学附属黑色素瘤转诊中心。
总共114例新诊断的皮肤恶性黑色素瘤患者，存在区域淋巴结转移风险。
黑色素瘤复发和总生存期。
23例患者（20%）的SLN病理检查呈阳性，所有这些患者的RT-PCR检测也呈阳性。在91例病理检查呈阴性的患者中，44例RT-PCR检测呈阴性，47例RT-PCR检测呈阳性。23例病理检查和RT-PCR检测均呈阳性的患者中有14例（61%）复发，44例病理检查和RT-PCR检测均呈阴性的患者中有1例（2%）复发。对于因分子检测而分期上调的患者（病理检查呈阴性，RT-PCR检测呈阳性），47例患者中有6例（13%）复发。病理检查呈阴性、RT-PCR检测呈阴性的患者组与病理检查呈阴性、RT-PCR检测呈阳性的患者组在复发率和总生存期方面的差异具有统计学意义（无病生存期和总生存期的P值均为0.02）。在单因素和多因素回归分析中，SLN的组织学和RT-PCR状态都是无病生存期的最佳预测指标。
与常规病理检查相比，使用RT-PCR检测SLN中的亚微观黑色素瘤转移可改善对黑色素瘤复发和总生存期的预测。
