PROTEOME PROFILING OF BLADDER SQUAMOUS-CELL CARCINOMAS - IDENTIFICATION OF MARKERS THAT DEFINE THEIR DEGREE OF DIFFERENTIATION

One hundred fifty fresh bladder tumors were analyzed blindly by two-di mensional PAGE in combination with proteome identification techniques (microsequencing and mass spectrometry) and immunofluorescence of cryo stat sections. Of these, six showed protein expression patterns corres ponding to squamous cell carcinomas (SCCs). All tumors were already in vasive at the time of presentation, and in most cases, the histopathol ogical grade could not be determined with certainty. The more differen tiated of the tumors included SCC 589-1, a lesion showing extensive ke ratinization, 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 kerati n 10, PA-FABP, and galectin 7 and, in addition, expressed keratins 13, 15, and 19, which were not detected in the pure SCC. Involucrin, glut athione S-transferase pi, stratifin (14-3-3 sigma), and the SCC antige n 1, on the other hand, were less abundant in SCC 589-1. In comparison , less-differentiated tumors did not express keratin 10 and were chara cterized 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 de gree 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, so lid tumor; SCC 485-1, special differentiation pattern). All six SCCs e xternalized psoriasin to the urine, supporting the contention that thi s protein, alone or in combination with other polypeptides, may repres ent a useful marker for the early detection of these lesions.