Kayser K, Hoeft D, Hufnagi P, Caselitz J, Zick Y, André S, Kaltner H, Gabius H-J
Institute of Pathology, Charité, Humboldt University, Berlin, Germany.
Histol Histopathol. 2003 Jul;18(3):771-9. doi: 10.14670/HH-18.771.
The aim of this study was to glyco- and immunohistochemically analyze expression of distinct growth/adhesion-related markers of primary testicular carcinomas and their lung metastases in relation to the risk of developing lung metastases and survival of patients, and to correlate immunohistochemical staining profile and syntactic structure analysis in order to delineate new prognostic parameters for this tumor type. Clinical features of 50 patients with primary testicular carcinomas and their corresponding lung metastases were evaluated and compared to those of a control cohort of 25 cases. The set of eight probes including labeled galectins-1 and -3, specific non-cross-reactive antibodies against galectins-1, -3, and -8 as well as anti-Ki-67, anti-bcl-2, and anti-p53 was applied to formalin-fixed, paraffin-embedded tumor sections of both primary and metastatic lesions. Syntactic structure analysis computed staining intensities and structural features of the tumor cells. These parameters were set into relation separately and in combination to clinical data including tumor stages, smoking habits, applied cytostatic therapy, disease-free interval, and survival. The risk of testis cancer patients to develop lung metastases depends in descending order on the tumor cell type (non-seminoma versus seminoma), tumor cell heterogeneity (mixed versus monomorphous cell type), age of patients, and pT stage. The extent of differential expression of galectin-related features between primary and secondary lesions was pronounced. Prognostic correlations for distinct galectin-related features were delineated in combination with data from syntactic structure analysis, for example cluster radius of galectin-3-positive tumor cells and post-surgical and total survival. Lengths of disease-free interval and total survival of patients were also correlated to characteristics obtained by syntactic structure analysis and their combination with galectin data in the first place, then to smoking habits, percentage of proliferating cells in the primary and secondary tumors, and finally to expression of certain galectins and of p53. Patients with non-seminoma testicular cancer should be thoroughly controlled for lung metastases. Regarding marker selection, our study underscores that further investigation of the growth-regulatory network of galectins is clearly warranted.
本研究的目的是通过糖基化和免疫组织化学分析原发性睾丸癌及其肺转移灶中不同生长/黏附相关标志物的表达情况,探讨其与肺转移风险及患者生存率的关系,并将免疫组织化学染色特征与句法结构分析相关联,以确定该肿瘤类型的新预后参数。评估了50例原发性睾丸癌患者及其相应肺转移灶的临床特征,并与25例对照队列的特征进行比较。将包括标记的半乳糖凝集素-1和-3、针对半乳糖凝集素-1、-3和-8的特异性非交叉反应抗体以及抗Ki-67、抗bcl-2和抗p53的8种探针组应用于原发性和转移性病变的福尔马林固定、石蜡包埋肿瘤切片。句法结构分析计算肿瘤细胞的染色强度和结构特征。将这些参数分别或联合与包括肿瘤分期、吸烟习惯、应用的细胞抑制疗法、无病间期和生存率等临床数据进行关联。睾丸癌患者发生肺转移的风险依次取决于肿瘤细胞类型(非精原细胞瘤与精原细胞瘤)、肿瘤细胞异质性(混合细胞型与单形细胞型)、患者年龄和pT分期。原发性和继发性病变之间半乳糖凝集素相关特征的差异表达程度显著。结合句法结构分析数据,确定了不同半乳糖凝集素相关特征的预后相关性,例如半乳糖凝集素-3阳性肿瘤细胞的簇半径与术后生存率和总生存率。患者的无病间期和总生存长度首先也与句法结构分析获得的特征及其与半乳糖凝集素数据的联合相关,其次与吸烟习惯、原发性和继发性肿瘤中增殖细胞的百分比相关,最后与某些半乳糖凝集素和p53的表达相关。非精原细胞瘤性睾丸癌患者应彻底检查是否有肺转移。关于标志物选择,我们的研究强调,显然有必要进一步研究半乳糖凝集素的生长调节网络。