Glycophenotype of bone metastases of prostatic carcinomas

Abstract

The significant morbidity and mortality associated with prostate cancer can universally be attributed to the consequences of metastases. Among prostatic carcinomas, there is a subset of neoplasms which invade bone, while other subsets do not, at least before the patient dies. Those tumours that can invade bone form a prognostically adverse group, but they cannot yet be identified before metastasis to bone has occurred. Therefore, markers capable of predicting tumour progression are required to avoid unnecessary treatment. This study aimed to define the changes in glycan expression occurring during the progression of metastatic prostatic carcinoma and investigate the biological role of fucosylated and sialylated glycans in the progression of prostatic carcinoma and its metastases, especially to bone. Blocks from 29 necropsy cases of prostatic carcinoma, including 62 deposits, were sectioned and stained with H&E, five biotinylated lectins: AAA, UEA-1, DBA, MAA and SNA using a lectin-biotin avidin-peroxidase method, and monoclonal antibodies against prostate specific antigen, Lewisa, sialyl Lewisa and sialyl Lewisx antigens. The results showed differences in the glycophenotype between the primary sites and the metastases. Those cells that metastasised to bone had a distinct glycophenotype, which was demonstrated by the absence or masking of almost all fucosyl residues (i.e. not recognised by AAA and UEA-1). The prostatic cancer cells in sclerotic bone metastases failed to demonstrate Lewis antigens, which were present in all the corresponding primary lesions. On the other hand, non-bone metastases showed a variable expression of the antigens both in the primary lesion and in the metastatic deposits. The findings of this study showed that bone metastasis is associated with two very different glycan phenotypes, the first in the primary tumours and the second in the bone metastases. This study also showed that prostatic metastatic tumours apart from bone metastases have glycophenotype that, in some metastases, are similar to those of the primary sites while in others they are similar to that of the bone metastases.