Ostergaard M, Rasmussen H H, Nielsen H V, Vorum H, Orntoft T F, Wolf H, Celis J E
Department of Medical Biochemistry and Danish Centre for Human Genome Research, The University of Aarhus, Aarhus C.
Cancer Res. 1997 Sep 15;57(18):4111-7.
One hundred fifty fresh bladder tumors were analyzed blindly by two-dimensional PAGE in combination with proteome identification techniques (microsequencing and mass spectrometry) and immunofluorescence of cryostat sections. Of these, six showed protein expression patterns corresponding to squamous cell carcinomas (SCCs). All tumors were already invasive at the time of presentation, and in most cases, the histopathological grade could not be determined with certainty. The more differentiated of the tumors included SCC 589-1, a lesion showing extensive keratinization, and 536-1, a pure SCC that resembled normal skin growing invasively into the muscle. Both tumors expressed keratins 5, 6, 10, 14, 16, 17, and 20, as well as the differentiation-associated proteins psoriasin, psoriasis-associated fatty acid-binding protein (PA-FABP), and galectin 7. SCC 589-1, however, exhibited higher levels of keratin 10, PA-FABP, and galectin 7 and, in addition, expressed keratins 13, 15, and 19, which were not detected in the pure SCC. Involucrin, glutathione S-transferase pi, stratifin (14-3-3 sigma), and the SCC antigen 1, on the other hand, were less abundant in SCC 589-1. In comparison, less-differentiated tumors did not express keratin 10 and were characterized by a decreased expression of keratin 14, psoriasin, PA-FABP, galectin 7, and stratifin (14-3-3 sigma). Indeed, two of these lesions (553-1 and 651-1) could be readily lined up in order of decreasing degree of differentiation based on the expression of these markers. The degree of differentiation of the other two SCCs could not be assessed with certainty because they may represent special cases (SCC 646-1, solid tumor; SCC 485-1, special differentiation pattern). All six SCCs externalized psoriasin to the urine, supporting the contention that this protein, alone or in combination with other polypeptides, may represent a useful marker for the early detection of these lesions.
采用二维聚丙烯酰胺凝胶电泳结合蛋白质组鉴定技术（微量测序和质谱分析）以及冷冻切片免疫荧光法，对150例新鲜膀胱肿瘤进行了盲法分析。其中，6例呈现出与鳞状细胞癌（SCC）相符的蛋白质表达模式。所有肿瘤在送检时均已发生浸润，在大多数情况下，无法确切判定其组织病理学分级。分化程度较高的肿瘤包括SCC 589 - 1，该病变显示出广泛的角化，以及536 - 1，一种纯SCC，类似于侵袭性生长至肌肉中的正常皮肤。这两种肿瘤均表达角蛋白5、6、10、14、16、17和20，以及分化相关蛋白银屑素、银屑病相关脂肪酸结合蛋白（PA - FABP）和半乳糖凝集素7。然而，SCC 589 - 1中角蛋白10、PA - FABP和半乳糖凝集素7的表达水平更高，此外，还表达了在纯SCC中未检测到的角蛋白13、15和19。另一方面，包壳蛋白、谷胱甘肽S - 转移酶π、层粘连蛋白（14 - 3 - 3σ）和SCC抗原1在SCC 589 - 1中的含量较低。相比之下，分化程度较低的肿瘤不表达角蛋白10，其特征是角蛋白14、银屑素、PA - FABP、半乳糖凝集素7和层粘连蛋白（14 - 3 - 3σ）的表达降低。实际上，基于这些标志物的表达，其中两个病变（553 - 1和651 - 1）可以很容易地按照分化程度降低的顺序排列。另外两个SCC的分化程度无法确切评估，因为它们可能代表特殊情况（SCC 646 - 1，实体瘤；SCC 485 - 1，特殊分化模式）。所有6例SCC均将银屑素分泌到尿液中，支持了这种蛋白质单独或与其他多肽结合可能代表这些病变早期检测有用标志物的观点。
