Denninghoff Valeria C, Falco Jorge, Kahn Andrea G, Trouchot Víctor, Curutchet Hector P, Elsner Boris
Department of Pathology, Center for Medical Education and Clinical Investigation, Buenos Aires, Argentina.
Mod Pathol. 2008 Apr;21(4):438-44. doi: 10.1038/modpathol.3801020. Epub 2008 Jan 25.
Lymph node mapping and sentinel lymph node biopsy are currently used to stage patients with cutaneous malignant melanoma. Immunohistochemical stains contribute to the detection of micrometastases; however, molecular biology techniques are associated with better diagnostic sensitivity. Sixty sentinel lymph nodes were included in this study. The primary lesions were malignant melanoma stage I or II, with a follow-up of longer than 2 years. Sentinel lymph nodes were studied with hematoxylin-eosin, immunohistochemistry for S-100 and HMB-45, and molecular biology techniques (reverse transcription (RT)-PCR) for the detection of tyrosinase messenger RNA. In 15 of 60 cases (25%), tyrosinase was detected by RT-PCR; three of these cases were also positive by immunohistochemistry. The population was divided into three groups: (i) hematoxylin-eosin-/immunohistochemistry+/molecular biology techniques+ (3 cases); (ii) hematoxylin-eosin-/immunohistochemistry-/molecular biology techniques+ (12 cases); (iii) hematoxylin-eosin-/immunohistochemistry-/molecular biology techniques- (45 cases). Correlation of the groups with overall survival showed the following: (i) 2 of 3 patients died (67%); (ii) 5 of 12 died (42%), and (iii) all 45 patients are alive, with no lymphadenectomy and a median follow-up of 84 months. The inclusion of molecular biology techniques appears to be of great value for the detection of sentinel lymph node micrometastases in patients with cutaneous malignant melanoma. In our series, those patients who showed negativity with all the three methods had a null recurrence rate. Therefore, this triple negativity could be a positive prognostic factor for overall survival. Our findings suggest the possibility of molecular oncological staging, which would allow the selection of patients with submicroscopic metastases for a complete treatment.
淋巴结图谱绘制和前哨淋巴结活检目前用于对皮肤恶性黑色素瘤患者进行分期。免疫组织化学染色有助于微转移灶的检测；然而，分子生物学技术具有更高的诊断敏感性。本研究纳入了60个前哨淋巴结。原发灶为I期或II期恶性黑色素瘤，随访时间超过2年。对前哨淋巴结进行苏木精-伊红染色、S-100和HMB-45免疫组织化学检测以及用于检测酪氨酸酶信使核糖核酸的分子生物学技术（逆转录（RT）-PCR）。60例中有15例（25%）通过RT-PCR检测到酪氨酸酶；其中3例免疫组织化学检测也呈阳性。研究对象分为三组：（i）苏木精-伊红染色阴性/免疫组织化学阳性/分子生物学技术阳性（3例）；（ii）苏木精-伊红染色阴性/免疫组织化学阴性/分子生物学技术阳性（12例）；（iii）苏木精-伊红染色阴性/免疫组织化学阴性/分子生物学技术阴性（45例）。各组与总生存率的相关性如下：（i）3例患者中有2例死亡（67%）；（ii）12例中有5例死亡（42%），（iii）45例患者均存活，未进行淋巴结清扫，中位随访时间为84个月。分子生物学技术的应用对于检测皮肤恶性黑色素瘤患者前哨淋巴结微转移灶似乎具有重要价值。在我们的系列研究中，三种方法均为阴性的患者无复发率。因此，这种三联阴性可能是总生存的一个阳性预后因素。我们的研究结果提示了分子肿瘤学分期的可能性，这将有助于选择有亚显微镜下转移的患者进行完整治疗。
