Department of Clinical Sciences, Division of Pathology, Lund University, Skåne University Hospital, 221 85 Lund, Sweden.
Biol Sex Differ. 2012 Jul 2;3(1):16. doi: 10.1186/2042-6410-3-16.
Malignant melanoma is the most deadly form of skin cancer. Female sex is known to have a protective effect on incidence, tumour characteristics, and mortality from melanoma. However, the potentially modifying effect of sex on the prognostic significance of clinicopathological and investigative factors is generally not taken into consideration in biomarker studies. In this study, we compared the sex-specific distribution and prognostic value of established tumour characteristics and Ki67 expression in 255 cases of incident primary melanoma in a prospective, population-based cohort study.
The study included 255 incident cases of melanoma, 132 females and 123 males, in the Malmö Diet and Cancer Study. Tumours from 226 (88.6%) cases had been assembled in tissue microarrays. Clinicopathological factors and immunohistochemical Ki67 expression were assessed and correlated with disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier analysis, log rank test and univariable and multivariable Cox regression analyses, stratified for gender. Effect of gender on melanoma-specific survival (MSS) after first recurrence was also analysed.
Women were significantly younger at diagnosis than men (p = 0.012). The most common tumour sites were the legs in women (37.5%) and the dorsal trunk in men (37.8%). Kaplan-Meier analysis revealed that tumour location had no prognostic impact in women, but in men, location to the frontal trunk was significantly associated with a reduced DFS compared with all other locations combined and location to the dorsal trunk was significantly associated with a prolonged OS. High Ki67 expression was significantly associated with a reduced DFS and OS in men but not in women, also when adjusted for other factors. In men, but not in women, ulceration was an independent prognostic factor for both DFS and OS. MSS after first local, regional or distant recurrence was significantly shorter for men than for women.
The results from this study demonstrate that the prognostic value of tumour location, Ki67 expression and ulceration in melanoma differs according to gender. These findings need to be validated in future studies, as they may help improve prognostication in patients with melanoma. Moreover, our findings demonstrate that sex-stratified analyses add valuable information to biomarker studies.
恶性黑色素瘤是最致命的皮肤癌形式。已知女性对黑色素瘤的发病率、肿瘤特征和死亡率具有保护作用。然而，在生物标志物研究中，通常没有考虑到性别对临床病理和研究因素预后意义的潜在修饰作用。在这项研究中，我们比较了 255 例原发性黑色素瘤病例的性别特异性分布和既定肿瘤特征和 Ki67 表达的预后价值，这些病例来自一项前瞻性、基于人群的队列研究。
该研究包括 255 例黑色素瘤病例，其中女性 132 例，男性 123 例，来自马尔默饮食与癌症研究。226 例（88.6%）病例的肿瘤已被组装成组织微阵列。使用 Kaplan-Meier 分析、对数秩检验以及单变量和多变量 Cox 回归分析，评估临床病理因素和免疫组织化学 Ki67 表达，并与无病生存（DFS）和总生存（OS）相关，同时按性别分层。还分析了性别对首次复发后黑色素瘤特异性生存（MSS）的影响。
女性的诊断年龄明显小于男性（p=0.012）。最常见的肿瘤部位是女性的腿部（37.5%）和男性的背部（37.8%）。Kaplan-Meier 分析显示，在女性中，肿瘤位置没有预后影响，但在男性中，与所有其他位置相比，前躯干位置与 DFS 缩短显著相关，与背部位置与 OS 延长显著相关。高 Ki67 表达与男性的 DFS 和 OS 降低显著相关，但在女性中没有，即使在调整其他因素后也是如此。在男性中，但在女性中，溃疡是 DFS 和 OS 的独立预后因素。与女性相比，首次局部、区域或远处复发后的 MSS 明显缩短。
本研究结果表明，肿瘤位置、Ki67 表达和溃疡在黑色素瘤中的预后价值因性别而异。这些发现需要在未来的研究中验证，因为它们可能有助于改善黑色素瘤患者的预后。此外，我们的研究结果表明，性别分层分析为生物标志物研究提供了有价值的信息。
