Gudmund Waaler

Impact of a tertiary Gleason pattern 4 or 5 on clinical failure and mortality after radical prostatectomy for clinically localised prostate cancer.

Study Type – Prognosis (case series)

Is the clinical malignant phenotype of prostate cancer a result of a highly proliferative immune-evasive B7-H3-expressing cell population?

Objectives:  To assess the expression of the cell surface protein B7‐H3 in prostate cancer, and its association to clinically relevant parameters after radical prostatectomy and to the proliferation marker Ki‐67.

Does a tertiary Gleason pattern 4 or 5 influence the risk of biochemical relapse after radical prostatectomy for clinically localized prostate cancer

Abstract Objective. The presence of a tertiary Gleason grade (TGG) pattern 4 or 5 in radical prostatectomy (RP) specimens has been reported with adverse pathology and a higher biochemical relapse rate after RP. This study investigated the impact of a TGG pattern 4 or 5 on biochemical and pathological outcome in men operated with RP. Material and methods. The study reviewed 151 consecutive cases treated at the hospital between 1985 and 2006; 148 were included in the study. All prostatectomy specimens were re-examined by a genitourinary pathologist and among others parameters the presence of TGG pattern 4 or 5 was recorded. The hospital files were examined retrospectively for clinical follow-up data. Prostate-specific antigen (PSA) relapse was defined as two subsequent rising measurements above 0.20 ng/ml. The influence of a TGG pattern 4 or 5 on prognosis was assessed in a Cox proportional hazards regression model controlling for pathological stage, surgical margin (SM) status, seminal vesicle invasion (SVI) and extraprostatic extension (EPE). Results. Fifty-six patients (38%) experienced PSA relapse during follow-up. Twenty-one patients (58%) with a TGG pattern 4 or 5 had a biochemical relapse compared with 35 patients (31%) without TGG pattern 4 or 5. In the Cox regression model, TGG pattern 4 or 5 was an independent predictor of biochemical failure (p = 0.020). Conclusions. In patients undergoing RP the presence of a TGG pattern 4 or 5 is an independent predictor for biochemical relapse. Consequently, the RP specimens should routinely be investigated for TGG pattern 4 or 5.

The prognostic value of reactive stroma on prostate needle biopsy: A population-based study

Reactive tumor stroma has been shown to play an active role in prostatic carcinogenesis. A grading system for reactive stroma in prostate cancer (PC) has recently been established and found to predict biochemical recurrence and prostate cancer‐specific mortality (PCSM) in prostatectomized patients. To the best of our knowledge, there has been no study investigating the prognostic value of reactive stromal grading (RSG) with regard to PCSM when evaluated in diagnostic prostate needle biopsies.

The prognostic value of reactive stroma on prostate needle biopsy

Reactive tumor stroma has been shown to play an active role in prostatic carcinogenesis. A grading system for reactive stroma in prostate cancer (PC) has recently been established and found to predict biochemical recurrence and prostate cancer‐specific mortality (PCSM) in prostatectomized patients. To the best of our knowledge, there has been no study investigating the prognostic value of reactive stromal grading (RSG) with regard to PCSM when evaluated in diagnostic prostate needle biopsies.

SHBG Is an Important Factor in Stemness Induction of Cells by DHT In Vitro and Associated with Poor Clinical Features of Prostate Carcinomas

Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression.

The relationship between perineural invasion, tumor grade, reactive stroma and prostate cancer-specific mortality: A clinicopathologic study on a population-based cohort

In vitro and in vivo studies have shown that nerves, tumor epithelium, and stroma interact and promote prostate cancer (PC) progression. Perineural invasion (PNI) is established amidst these interactions and may therefore indicate an aggressive PC phenotype. The purpose of the present study was to determine the relationship between PNI, tumor grade, reactive stroma, and PC‐specific mortality.

The Length of a Positive Surgical Margin Is of Prognostic Significance in Patients with Clinically Localized Prostate Cancer Treated with Radical Prostatectomy

Objective: To establish predictors of clinical failure in patients operated with radical prostatectomy (RP) for clinically localized prostate cancer (PC) by analyzing the pathological characteristics of positive surgical margins (PSM). Patients and Methods: The RP specimens of 303 consecutive patients operated with RP between 1985 and 2009 were reviewed. PSM were analyzed with regard to the PSM length, location and multifocality and the Gleason score (GS) at the PSM. Results: Of the 163 patients with PSM, 79 (48%) progressed to clinical failure compared to 30 (22%) in the negative-margin-status group. In univariate analysis, a GS at the PSM ≥4 + 3 = 7 (p = 0. 013) and a PSM length >3.0 mm (p < 0.005) were significantly associated with higher clinical failure rates compared to a GS at the PSM ≤3 + 4 = 7 and ≤3.0 mm in extent, respectively. A linear extent of the PSM ≤3.0 mm appeared to have the same clinical outcome as in the group with a negative margin status. In multivariate analysis, a PSM length >3.0 mm remained an independent predictor of clinical failure. Conclusions: PSM length is an independent predictor of clinical failure following RP.

Prostatic Cancer in Aust-Agder County, Norway: Age, Stage, Grade and Mode of Presentation

Two hundred and five patients (89 per 100,000 men) with newly diagnosed prostatic cancer comprises all cases in the Aust-Agder County in Norway over a 5-year period. There were 36% stage T0 M0, 19% T1-2 M0, 16% T3-4 M0 and 29% T0-4 M1. In patients with well differentiated disease (G1), 8% had distant metastases on presentation, whereas in the moderately differentiated tumors (G2) and the poorly differentiated tumors (G3) distant metastases occurred in 30% and 62%, respectively. A statistically significantly higher proportion of well differentiated (G1) tumors were observed in the younger age groups (less than 70 years). On presentation diagnosis was suspected on routine digital rectal examination in 9% of the patients, while 12% had symptoms on disseminated disease as mode of presentation. Of patients operated upon for apparently benign hyperplasia 13% had prostatic cancer.

Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study

Intraductal carcinoma of the prostate (IDC‐P) is a distinct histopathologic feature associated with high‐grade, advanced prostate cancer. Although studies have shown that IDC‐P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC‐P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality.