Novel Biomarker Panel Accurately Predicts Prostate Cancer Outcomes

According to new research published in Cancers, the use of immunohistochemistry (IHC) to label intercellular biomarkers helps improves Gleason score interpretation and prognostic predictions for patients with prostate cancer.

Prostate cancer is primarily assessed by the Gleason grading of hematoxylin and eosin-stained (H&E) tissue. The Gleason system measures the relative abnormality of prostate cancer cells and influences disease-state grading provided by the International Society of Urological Pathology (ISUP—which grades on a scale of 1-5, with higher scores signifying an increased probability a patient’s cancer will spread).

Gleason/ISUP grading using H&E has been useful for evaluating the risk of post-prostatectomy clinical recurrence (CR) and biochemical recurrence (BCR) in patients with prostate cancer. However, the authors mention that this method is viewed as “highly subjective” and inadequate for completely exploring the complex pathology of prostate cancer.

Aiming to improve patient treatment through better risk stratification, researchers utilized APPL1, sortilin, and syndecan-1 (biomarkers stemming from the endosome-lysosome system) to better assess the cell biology correlating with varying stages of prostate cancer and assign ISUP grades. These biomarkers help doctors visualize cancerous tissue more effectively, therefore improving their ability to predict patient outcomes.

Data were gathered from the Australian Prostate Cancer Bioresource between January 2006 and August 2014. Researchers analyzed radical prostatectomy tissue samples from 114 patients with prostate cancer. Patients ranged from 45-75 years of age and had prostate-specific antigen (PSA) levels above 0.2 ng/mL. Clinical follow up on metastatic disease progression/CR and BCR was available for a minimum of 10 years after their surgery.

Tissue samples were divided into 4 sections: section 1 was stained according to standard H&E methods, the 3 remaining sections were IHC-labelled with APPL1, sortilin, and syndecan-1. CR outcomes were defined as the time period between the day of radical prostatectomy to the day of clinical disease progression. BCR outcomes were defined as the time period from the day of radical prostatectomy to either the day of 2 consecutive PSA elevations above 0.2 ng/mL, day of androgen deprivation therapy following a PSA elevation that stayed below 0.2 ng/mL, or the initiation of radiation therapy (both groups’ predictive probabilities were measured with C-statistics).

Between the 2 methods, the IHC-assisted ISUP groups gave more accurate predictions than H&E ISUP in both CR (C-statistic = 0.71 vs 0.66) and BCR (C-statistic = 0.63 vs 0.59). As researchers conducted an adjusted analysis, they also found that the IHC-assisted ISUP groups were independently and significantly linked to CR (P = .009) and BCR (P = .02) predictions. This statistical significance was not observed within the H&E ISUP groups.

Many of the initial ISUP grades given in line with patients’ H&E slides were reclassified upon the assessment of their IHC slides. For patients whose samples were up-classified in ISUP grade, their predicted risk of CR rose from 8% to 22%. Predicted BCR risks also grew for patients that were up-classified, rising from 39% to 61%, respectively. Overall, patients who were up-classified in ISUP all trended towards worse outcomes than the patients who kept their original ISUP classification.

The findings demonstrated the potential benefits of new biomarker technology for prostate cancer risk stratification. IHC-assisted grading with APPL1, sortilin, and syndecan-1 all presented more accurate prognosis for patients with prostate cancer. The authors believe the implications of their study are “critical” for the future of predicting patient outcomes.

Since their study was retrospective in nature, they urge for research with larger, real-world cohorts to further investigate the impact of biomarker technology on patient treatment and long-term survival outcomes.

Reference

Logan JM, Hopkins AM, Martini C, et al. Prediction of prostate cancer biochemical and clinical recurrence is improved by IHC-assisted grading using Appl1, Sortilin and Syndecan-1. Cancers. June 16, 2023;15(12). doi: 10.3390/cancers15123215