A retrospective study of high mobility group protein I(Y) as progression marker for prostate cancer determined by in situ hybridization.

In a previous study using RNA in situ hybridisation (RISH), we found a significant correlation between high mobility group protein I/Y, [HMG-I(Y)] mRNA expression and tumour stage and grade in prostate cancer patients, suggesting that HMG-I(Y) might be a potential prognostic marker in prostate cancer. However, our clinical follow-up was limited because cryopreserved material was used. Assessing the potential prognostic value of this molecule is of importance because the clinical course of prostate cancer patients remains unpredictable. Here we describe our results on paraffin-embedded archival material from a group of 102 patients undergoing radical prostatectomy. These were evaluated for the presence of HMG-I(Y) using RISH, and a follow-up of 12-92 months (average 53 months) was available. In 2 of 14 prostate cancers in which the predominant histological pattern was of Gleason grade 1-2, a high HMG-I(Y) expression was observed, whereas in 19 of 23 Gleason grade 3, and 34 of 35 Gleason grade 4-5 tumours, high HMG-I(Y) mRNA levels were detected (chi-square = 38.78, P < 0.0001). Moreover, of tumours that expressed high HMG-I(Y) levels, 25% were organ confined (T1-2), in contrast to 74.5% of the invading tumours (T3, chi-square = 15.8, P < 0.001). Furthermore, 87% of recurrent tumours showed high HMG-I(Y) expression. However, a multivariate regression analysis including Gleason grade, clinical tumour stage, HMG-I(Y) expression and prostate-specific antigen (PSA) levels showed Gleason grade as the most accurate predictor of progression. High HMG-I(Y) levels measured by RISH were indicative of a worse prognosis, albeit that additional value over the more subjective grading methods was not evident.