Background: The clinical value of heat-induced coagulation of prostatic tissue is evaluated as a minimally invasive treatment for patients with benign prostatic hyperplasia (BPH) and, more recently, localized prostate cancer (PC). To obtain a more detailed insight on the effect of heat on prostatic cells, heat shock protein (HSP) 27 expression of normal and malignant prostatic cells was studied.
Methods: In vitro, HSP27 expression of prostatic stromal cells and the human prostate cancer cell line LNCaP was studied by Western blotting when cultured at 37 degrees C. Subsequently, the effect of a sublethal heat shock from 43-49 degrees C for 60 min on HSP27 expression of LNCaP was determined. In vivo, HSP27 expression pattern of nine human prostates, which were treated in vivo by thermoablation with transrectal high-intensity focused ultrasound (HIFU) 3 hr-8 days prior to surgical removal, was analyzed by immunohistochemistry. Untreated BPH (n = 10) and PC (n = 7) specimens served as controls.
Results: Under physiologic conditions (37 degrees C), LNCaP and prostatic stromal cells expressed a 27-kD and 56-kD anti-HSP27 reactive molecule. Following sublethal cell heating, HSP27 (27 kD) expression of LNCaP increased by 3-4-fold in a temperature-dependent manner. In untreated BPH specimens (n = 10), muscle cells stained HSP27-positive in all samples, while epithelial cells (EC) were negative in 6 out of 10 specimens. At the border of the high-intensity focused ultrasound (HIFU) necrosis, increased HSP27 expression was consistently demonstrable (n = 9). HSP27 upregulation was strongest 2-3 hr after HIFU but still demonstrable after 5-8 days. In this border zone, basal and secretory EC as well as muscle cells stained strongly for HSP27.
Conclusions: Benign and malignant human prostatic cells respond to heat by increased expression of HSP27 in vitro and in vivo. Transrectal HIFU therapy induces intraprostatic thermonecrosis surrounded by a zone characterized by a massive upregulation of HSP27 expression.