Kammula Udai S, Ghossein Ronald, Bhattacharya Satyajit, Coit Daniel G
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
J Clin Oncol. 2004 Oct 1;22(19):3989-96. doi: 10.1200/JCO.2004.03.052.
Reverse transcriptase-polymerase chain reaction (RT-PCR) may provide an extremely sensitive method for detection of occult nodal disease. We evaluated the role of a single-marker RT-PCR assay for tyrosinase mRNA in the detection of melanoma sentinel lymph node (SLN) metastases and correlated the results with long-term clinical outcome.
One hundred twelve patients who underwent SLN biopsy for melanoma were prospectively analyzed. SLNs were bivalved, with half of each specimen evaluated by histologic methods and the other half evaluated by nested RT-PCR for tyrosinase.
Fifteen patients (13%) had histologically positive SLNs, all of whom were also positive by RT-PCR (HISTO+/PCR+). Thirty-nine patients (35%) had SLNs that were negative by both histology and RT-PCR (HISTO-/PCR-). Fifty-eight patients (52%) were histologically negative but upstaged with a positive RT-PCR result (HISTO-/PCR+). Initially, at a median follow-up of 42 months, recurrence rates among the three cohorts were statistically different (HISTO+/PCR+, 53%; HISTO-/PCR+, 14%; and HISTO-/PCR-, 0%). However, at a longer median follow-up (67 months), recurrence rates for the HISTO-/PCR+ (24%) and HISTO-/PCR- (15%) groups were no longer statistically different (P =.25). The median time to relapse between the HISTO-/PCR+ and HISTO-/PCR- groups differed by 10 months (31 v 41 months, respectively).
With extended follow-up of patients with histologically negative SLNs, detection of submicroscopic disease by tyrosinase RT-PCR does not define a subgroup that is at higher recurrence risk when compared with patients with RT-PCR-negative SLNs. Future studies evaluating molecular staging will require approximately 5 years of median follow-up to accurately define outcome for patients with occult melanoma metastases.
逆转录酶-聚合酶链反应(RT-PCR)可能为检测隐匿性淋巴结疾病提供一种极其灵敏的方法。我们评估了酪氨酸酶信使核糖核酸(mRNA)单标记RT-PCR检测法在黑色素瘤前哨淋巴结(SLN)转移检测中的作用,并将结果与长期临床结局相关联。
对112例行黑色素瘤SLN活检的患者进行前瞻性分析。将SLN切成两半,每个标本的一半通过组织学方法评估,另一半通过巢式RT-PCR检测酪氨酸酶。
15例患者(13%)的SLN组织学检查呈阳性,所有这些患者的RT-PCR检测也呈阳性(组织学阳性/PCR阳性)。39例患者(35%)的SLN组织学和RT-PCR检测均为阴性(组织学阴性/PCR阴性)。58例患者(52%)组织学检查为阴性,但RT-PCR结果为阳性,从而进行了分期上调(组织学阴性/PCR阳性)。最初,中位随访42个月时,三组患者的复发率在统计学上存在差异(组织学阳性/PCR阳性组为53%;组织学阴性/PCR阳性组为14%;组织学阴性/PCR阴性组为0%)。然而,在更长的中位随访期(67个月)时,组织学阴性/PCR阳性组(24%)和组织学阴性/PCR阴性组(15%)的复发率不再具有统计学差异(P = 0.25)。组织学阴性/PCR阳性组和组织学阴性/PCR阴性组之间的中位复发时间相差10个月(分别为31个月和41个月)。
对组织学检查阴性的SLN患者进行延长随访后,与RT-PCR检测阴性的SLN患者相比,通过酪氨酸酶RT-PCR检测到亚显微镜下疾病并不能确定复发风险更高的亚组。未来评估分子分期的研究需要约5年的中位随访期,以准确确定隐匿性黑色素瘤转移患者的结局。