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 α6β4 integrin participates in the formation of hemidesmosomes, attaching epithelial cells to the basement membrane. Investigations of the α6β4 integrin in human prostatic carcinoma have yielded conflicting results and have been primarily qualitative rather than quantitative. Expression of the β4 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 β4 integrin subunit 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 β4 integrin subunit, and all 15 patients with PIN had downregulation of β4 in PIN as compared with BPE. Degree of downregulation of the β4 integrin subunit did not add prognostic significance to the information present at initial biopsy (age, 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 β4 integrin subunit staining with age, pathological stage, or Gleason's score. Downregulation of the β4 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.