Konstadoulakis M M, Vezeridis M, Hatziyianni E, Karakousis C P, Cole B, Bland K I, Wanebo H J
Department of Surgery, Brown University School of Medicine, Center for Statistical Science, Providence, Rhode Island, USA.
Ann Surg Oncol. 1998 Apr-May;5(3):253-60. doi: 10.1007/BF02303782.
Oncogenes and other molecular tumor markers that predict tumor aggressiveness may allow individualization and optimization of surgical therapy of intermediate-thickness malignant melanoma. We examined the expression of selected markers, including the HLA-DR antigen, the heat shock protein-70 (HSP-70), and the c-myc oncogene in primary melanoma and regional nodes and related these findings to metastatic potential and survival.
Forty patients with primary melanoma (1.5-4.0 mm) were studied, all of whom had prophylactic lymph node dissection and were followed for 18 months to 7 years. The primary tissue and nodes were examined using immunohistochemical techniques for the presence of HLA-DR antigen and HSP-70 protein and the expression of the c-myc oncogene.
Of 40 patients, there were 23 with lesions 1 to 2.9 mm thick and 17 with lesions 3 to 4 mm thick. Nodal metastases were present in 25 of the 40 patients who had elective node dissection. HLA-DR antibody stained the primary tumor in 10 patients (25%), but there was no correlation with survival in this group. HLA-DR antibody stained the stroma and cellular infiltrates surrounding the primary tumor in 28 of 40 patients; in this group there was a correlation of HLA-DR staining of the peritumoral stroma with improved survival overall. HLA-DR staining of the peritumoral stroma also influenced survival when patients were stratified by tumor thickness groups 1 to 2.9 mm and 3 to 4 mm and presence of nodal metastases. HSP-70 was demonstrated in the primary tumor in 25% of patients, who were also shown to have significantly improved survival when compared with those whose primary tumor did not stain with HSP-70. C-myc was expressed in the primary tumor in 25%, but showed no correlation with survival. None of these proteins correlated with or predicted the presence of nodal metastases.
We conclude that the use of specific molecular-oncogene markers in intermediate-thickness primary melanoma may identify patients at high risk for conventional treatment failure and reduced survival who may profit from more aggressive surgery, adjuvant therapy, or both.
癌基因及其他预测肿瘤侵袭性的分子肿瘤标志物可能有助于实现中间厚度恶性黑色素瘤手术治疗的个体化及优化。我们检测了包括HLA-DR抗原、热休克蛋白-70（HSP-70）以及c-myc癌基因在内的特定标志物在原发性黑色素瘤及区域淋巴结中的表达情况，并将这些结果与转移潜能及生存率相关联。
对40例原发性黑色素瘤（厚度为1.5 - 4.0 mm）患者进行研究，所有患者均接受了预防性淋巴结清扫，并随访18个月至7年。采用免疫组化技术检测原发组织及淋巴结中HLA-DR抗原的存在情况、HSP-70蛋白的表达情况以及c-myc癌基因的表达情况。
40例患者中，23例病变厚度为1至2.9 mm，17例病变厚度为3至4 mm。在40例行选择性淋巴结清扫的患者中，25例出现了淋巴结转移。HLA-DR抗体在10例患者（25%）的原发性肿瘤中呈阳性染色，但该组中其与生存率无相关性。HLA-DR抗体在40例患者中的28例原发性肿瘤周围的基质及细胞浸润中呈阳性染色；在该组中，肿瘤周围基质的HLA-DR染色与总体生存率的提高相关。当根据肿瘤厚度分组（1至2.9 mm和3至4 mm）及有无淋巴结转移对患者进行分层时，肿瘤周围基质的HLA-DR染色也影响生存率。25%的患者原发性肿瘤中检测到HSP-70，与原发性肿瘤未被HSP-70染色的患者相比，这些患者的生存率也显著提高。25%的患者原发性肿瘤中表达c-myc，但与生存率无关。这些蛋白均与淋巴结转移的存在无相关性或不能预测淋巴结转移情况。
我们得出结论，在中间厚度原发性黑色素瘤中使用特定的分子癌基因标志物可能识别出那些常规治疗失败风险高且生存率降低的患者，这些患者可能从更积极的手术、辅助治疗或两者结合中获益。
