DOWN-REGULATION OF THE BETA-4 INTEGRIN SUBUNIT IN PROSTATIC-CARCINOMAAND PROSTATIC INTRAEPITHELIAL NEOPLASIA

Integrins are adhesion receptors thought to be important in the proces s of cancer cell invasion and metastasis. Unlike other integrins, whic h attach a cell to extracellular matrix molecules, the alpha 6 beta 4 integrin participates in the formation of hemidesmosomes, attaching ep ithelial cells to the basement membrane. Investigations of the alpha 6 beta 4 integrin in human prostatic carcinoma have yielded conflicting results and have been primarily qualitative rather than quantitative. Expression of the beta 4 integrin subunit was determined using rat mo noclonal antibody 439-9B and image analysis in regions of benign prost atic epithelium (BPE), high-grade prostatic intraepithelial neoplasia (PIN), and prostatic carcinoma (CaP) in 38 patients treated by radical prostatectomy for clinically localized CaP. The beta 4 integrin submi t was significantly downregulated in CaP compared with BPE; PIN staine d intermediate in intensity between BPE and CaP. Thirty-four of 35 pat ients showed downregulation of the beta 4 integrin subunit, and all 15 patients with PIN had downregulation of beta 4 in PIN as compared wit h BPE. Degree of downregulation of the beta 4 integrin subunit did not add prognostic significance to the information present at initial bio psy tag, clinical stage, clinical grade, and serum prostate-specific a ntigen level). There was no correlation between intensity of staining of CaP, absolute change in staining, or percent loss of beta 4 integri n subunit staining with age, pathological stage, or Gleason's score. D ownregulation of the beta 4 integrin in CaP and PIN compared with BPE may be correlated with neoplastic transformation of the prostate and l oss of hemidesmosomes or basal epithelial cells. Copyright (C) 1998 by W.B. Saunders Company.