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A retrospective study of high mobility group protein I(Y) as progression marker for prostate cancer determined by in
Y Tamimi1, H G van der Poel, H F Karthaus
1Department of Urology/Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Abstract:
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.
Insights
High mobility group protein I/Y (HMG-I(Y)) mRNA expression correlates with advanced prostate cancer stages and recurrence. While HMG-I(Y) indicates a worse prognosis, Gleason grade remains the most accurate predictor of progression.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Research
Background:
- Prostate cancer prognosis is often unpredictable.
- High mobility group protein I/Y (HMG-I(Y)) has shown potential as a prognostic marker in prior studies.
- Previous research was limited by cryopreserved samples.
Purpose of the Study:
- To assess the prognostic value of HMG-I(Y) mRNA expression in paraffin-embedded prostate cancer tissue.
- To correlate HMG-I(Y) expression with tumor stage, grade, and patient outcomes.
Main Methods:
- RNA in situ hybridization (RISH) was used to quantify HMG-I(Y) mRNA levels.
- Archival paraffin-embedded tissues from 102 prostatectomy patients were analyzed.
- Clinical follow-up data ranged from 12-92 months (average 53 months).
Main Results:
- High HMG-I(Y) expression significantly correlated with higher Gleason grades (P < 0.0001).
- Elevated HMG-I(Y) levels were associated with invasive tumors (T3) and recurrent disease (87%).
- Multivariate analysis identified Gleason grade as the strongest predictor of progression.
Conclusions:
- High HMG-I(Y) mRNA levels indicate a worse prognosis in prostate cancer.
- HMG-I(Y) shows potential as a prognostic indicator, but its added value over Gleason grading requires further investigation.