Early metastatic progression of bladder carcinoma: molecular profile of primary tumor and sentinel lymph node.

Abstract

We characterized early metastatic progression of bladder carcinoma from the primary tumor, separated in the central part and invasive front, to the first lymphatic metastasis. Included in this study were 8 patients undergoing sentinel lymph node detection for invasive bladder cancer, of whom 4 had metastasis in the sentinel lymph node and 4 were randomly chosen without metastases. After microdissection p53 genomic structure and immunohistochemical expression of p53, pRB, Ki67 and E-cadherin were analyzed. Microvessel density and apoptosis were also assessed. In 5 patients there were p53 gene mutations in the primary tumor, while 3 had the wild-type gene. The genotypes were identical in the central part and invasive front. All sentinel lymph node metastases harbored p53 mutations, in contrast to all nonmetastatic sentinel lymph nodes. Two patients had the same mutation as the primary tumor and 1 had an additional mutation. In a patient with a wild-type gene in each compartment of the primary tumor a mutation appeared in the corresponding sentinel lymph node metastasis. There was poor concordance of p53 mutation with protein status. The expression of p53, pRB, Ki67, E-cadherin, and the evaluation of apoptosis and angiogenesis showed in most cases only slight variations in tumor compartments and the sentinel lymph node. In this study invasive bladder carcinoma involved monoclonal proliferations with a mainly homogenous biomarker profile. The first metastases in sentinel lymph nodes had a similar molecular profile but in half of the cases signs of clonal evolution appeared.