Downregulation of the β4 integrin subunit in prostatic carcinoma and prostatic intraepithelial neoplasia

Integrins are adhesion receptors thought to be important in the process of cancer cell invasion and metastasis. Unlike other integrins, which attach a cell to extracellular matrix molecules, the alpha 6 beta 4 integrin participates in the formation of hemidesmosomes, attaching epithelial 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 monoclonal antibody 439-9B and image analysis in regions of benign prostatic 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 submit was significantly downregulated in CaP compared with BPE; PIN stained intermediate in intensity between BPE and CaP. Thirty-four of 35 patients showed downregulation of the beta 4 integrin subunit, and all 15 patients with PIN had downregulation of beta 4 in PIN as compared with BPE. Degree of downregulation of the beta 4 integrin subunit did not add prognostic significance to the information present at initial biopsy tag, clinical stage, clinical grade, and serum prostate-specific antigen level). There was no correlation between intensity of staining of CaP, absolute change in staining, or percent loss of beta 4 integrin subunit staining with age, pathological stage, or Gleason's score. Downregulation of the beta 4 integrin in CaP and PIN compared with BPE may be correlated with neoplastic transformation of the prostate and loss of hemidesmosomes or basal epithelial cells. Copyright (C) 1998 by W.B. Saunders Company.