Pathology of SN and non-SN in Patients with Melanoma

项目I将继续通过提供专家咨询和密切质量来支持MSLT-I和MSLT-II 保障服务。使用这些试验的数据，我们将评估技术的病理方面 淋巴标测和前哨淋巴结(SN)活检，探讨SN的细胞和分子基础 对转移的易感性以及这种易感性背后的细胞和分子机制。 具体来说，与核心B合作的项目I人员将确认和分类初级黑色素瘤和 所有进入MSLT-II的患者的序列号。MSLT-I和MSLT4I的患者人口学特征 他们的原发黑色素瘤的特征，单独和合并到算法中，将被评估 预测肿瘤阳性SN的能力(组织学和/或分子阳性SN(项目II)，结外 黑色素瘤复发和死亡(项目III)。我们还将评估SN程度的影响 抽样调查阳性SN、结节(假阴性SN)、结外复发和死亡的频率 黑色素瘤)。我们还将研究黑色素瘤的特性和黑色素瘤免疫反应性 预测非黑色素瘤、随后的结外转移和死于黑色素瘤。这些 研究将包括分析黑色素瘤的数量和分布，细胞的生物学特性 副皮质细胞密度、树突性和成熟免疫表型的改变 树突状细胞、T淋巴细胞亚型和结节血管的评估。这些研究将是 与分子阳性的结节的预后预测潜力密切相关，但 组织学阴性(项目II)。此外，我们还将评估分子正性的基础 组织学阴性，通过组织学和组织学来详尽地评估这些患者的组织块 免疫组织学。我们将继续研究SN免疫下调的细胞和分子基础 通过评估免疫活性细胞的构成来评估对转移的易感性 肿瘤阳性和肿瘤阴性SN及自体原发肿瘤旁组织中的种群 黑色素瘤的免疫组织学和定量形态计量学研究。人与人之间关系的分子基础 原发性黑色素瘤及其相关免疫活性细胞与肿瘤阳性和阴性 SN将依赖于原代细胞及其相关细胞的细胞因子和趋化因子图谱 免疫组织化学和逆转录原位聚合酶链式反应。

Project I will continue to support MSLT-I and MSLT-II by providing expert consultation and close quality assurance services. Using data from these trials, we will evaluate pathological aspects of the techniques of lymphatic mapping and sentinel node (SN) biopsy, investigate the cellular and molecular basis of SN susceptibility to metastases and the cellular and molecular mechanisms that underlie that susceptibility. Specifically Project I personnel, working with Core B will confirm and categorise the primary melanomas and SN of all patients entering MSLT-II. Patient demographic characteristics for MSLT-I and MSLT4I and characteristics of their primary melanomas, singly and combined into algorithms, will be be evaluated for capacity to predict tumor-positive SN (histologically and/or molecularly-positive SN (Project II), extranodal recurrence and death from melanoma (with Project III).We will also assess the impact of extent of SN sampling on frequency of positive SN, nodal (false-negative SN) and extranodal recurrences and death from melanoma). We will also investigate the capacity of characteristics of SN tumor and SN immune reactivity to predict melanoma in non-SN, subsequent extranodal metastases and death from mealanoma. These studies wil include analysis of the amount and distribution of SN tumor, biological characteristics of the cells of SN metastases, alterations in the density, dendriticity and maturity immunophenotype of paracortical dendritic cells, subtyping of T lymphocytes and assessment of the nodal vasculature. These studies will be closely correlated with the outcome-predictive potential of nodes that are molecularly positive, but histologically negative (Project II). In addition, we will evaluate the basis of molecular-positivity in face of histological negativity, by exhaustively evaluating tissue blocks from such patients by histology and immunohistology. We will continue to investigate the cellular and molecular basis of SN immunedownregulation and susceptibility to metastases by assessing the constitution of immune competent cell populations in tumor-positive and tumor-negative SN and in the tissues adjacent to autologous primary melanomas by immunohistology and quanitative morphometry. The molecular basis of relationships between primary melanomas and immunologically active cells associated with them and tumor-positive and -negative SN will depend on cytokine and chemokine profiling of primaries and their associated cells by immunohistology and RT in situ PCR.