Prostate Cancer

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pulling prostrates

The results of this clinical study suggest that supplementation with vitamin D3 at 4000IU per day may benefit patients with early stage, low-risk prostate cancer on active surveillance, because of the improved outcome (a decreased number of positive cores at repeat biopsy) in more than half of the subjects enrolled in the trial.

A b s t r a c t
ERG rearrangements (most commonly
transmembrane protease, serine 2 [TMPRSS2]:ERG
[T2:ERG] gene fusions) have been identified in
approximately 50% of prostate cancers . Quantification
of T2:ERG in postdigital rectal examination urine, in
combination with PCA3, improves the performance
of serum prostate-specific antigen for prostate cancer
prediction on biopsy. Here we compared urine
T2:ERG and PCA3 scores with ERG+ (determined
with immunohistochemical analysis) and total
prostate cancer burden in 41 mapped prostatectomies.
Prostatectomies had a median of 3 tumor foci (range,
1-15) and 2.6 cm of summed linear tumor dimension
(range, 0.6-7.1 cm). Urine T2:ERG score correlated
most with summed linear ERG+ tumor dimension and
number of ERG+ foci (rs = 0.68 and 0.67, respectively,
both P < .001). Urine PCA3 score showed weaker
correlation with both number of tumor foci (rs =
0.34, P = .03) and summed linear tumor dimension
(rs = 0.26, P = .10). In summary, we demonstrate a
strong correlation between urine T2:ERG score and
total ERG+ prostate cancer burden at prostatectomy,
consistent with high tumor specificity.

http://www.nature.com/pcan/journal/v16/n2/full/pcan20134a.html

Abstract
Background: The TMPRSS2-ERG gene fusion resulting in ERG overexpression has been found in around 50% of prostate cancers (PCa) and is a very early event in tumorigenesis. Most studies have reported on selected surgical cohorts with inconsistent results. We hypothesized that ERG gene rearrangements impact tumor development and investigated the frequency of ERG overexpression in the context of clinicopathological tumor characteristics.
Methods: ERG overexpression (ERG+ or ERG-) was determined by immunohistochemistry (IHC) in 1039 radical prostatectomy (RP) tumors and association with PSA, D’Amico risk score, histopathology, biochemical recurrence, body mass index and age of PCa cases was analyzed.
Results: ERG+ was associated with younger age at diagnosis (P<0.0001), lower serum PSA (P=0.002) and lower prostate volume (PV) (P=0.001). It was most frequent in the youngest age quartile (55 years, 63.9% ERG+) and decreased constantly with increasing age to 40.8% in the oldest age quartile (67 years, P<0.0001). In the PSA range <4 ng ml−1 the frequency of ERG positivity was 60.2% compared with 47.5 and 49.1% in the PSA ranges 4–10 and 10 ng ml−1, respectively. In the first age quartile, ERG+ patients had lower median serum PSA and fPSA% and smaller PV. In the highest age quartile tumor volume (TV) was increased. Similar differences were observed in the low PSA range. Multivariate analysis identified the first age quartile as a predictor for ERG status (odds ratios (OR) 2.05, P=0.007). No association was found with the D’Amico progression risk score and with biochemical tumor recurrence.
Conclusions: ERG+ tumors manifest clinically at lower PSA levels and their prevalence is age dependent. This suggests acceleration of tumor development by ERG overexpression that results in earlier tumor detection in young patients. Long-term results are warranted to determine the impact of ERG overexpression on disease outcome.
Keywords: age; ERG frequency distribution; ERG overexpression; early-onset prostate cancer; PSA screening

Introduction

Prostate cancer (PCa) is the most common solid neoplasm in the developed countries accounting for almost 30% of cancer incident cases in men. It is the third leading cause of male cancer deaths in Europe1, 2 and second in the USA although an estimated 90% of newly diagnosed cases are local or regional with a 5-year relative survival approaching almost 100%.3 A frequently occurring genetic alteration of prostate tumors is a gene rearrangement involving transcription factors of the E26 transformation specific (ETS) family and an androgen-regulated gene. The most common event found in 40–60% of PCa cases results in the fusion of the transcription factor ERG and the androgen regulated transmembrane serine protease 2 (TMPRSS2) gene and leads to androgen-stimulated overexpression of ERG.4 Less common are rearrangements involving the ETS transcription factors ETV1, 4 and 5 or other androgen regulated 5′ partners such as SLC45A3.5

An ERG rearrangement regardless of the 5′ partner is highly specific for PCa and only found in tumor cells or a subset of high-grade prostatic intraepithelial neoplasia lesions.6, 7 Therefore, analysis of an ERG rearrangement is beginning to have a role in routine pathology.8, 9 The fusion status can reliably be determined using fluorescence in situ hybridization detecting the gene rearrangement,4, 10 by PCR measuring expression of a fusion transcript4 or using IHC detecting the overexpressed ERG protein.11 Positive immunohistochemical staining highly correlates with the ERG gene rearrangement status determined by fluorescence in situ hybridization or mRNA analyses.11, 12

The ERG rearrangement occurs early in prostate carcinogenesis7 and is then present at around the same frequency through all tumor stages up to metastatic, therapy-resistant disease.13 Despite numerous studies the implication of this common genetic alteration on tumor progression and consequences for the management and treatment of PCa have yet to be defined. This may in part be due to relative few studies that have focused on large well-characterized patient populations. The majority of studies reported no association between biochemical recurrence and ERG rearrangement status.14, 15 Conversely, population-based Watchful Waiting studies have found associations with PCa specific death.16, 17 Recent investigations suggested that gene-fusion driven ERG overexpression increases self-renewal and stimulates epithelial to mesenchymal transition.18, 19

We hypothesized that ERG overexpression is an early driver of tumor development and investigated the frequency of ERG overexpression in dependence on patient age and clinicopathological characteristics. The prevalence of ERG overexpression was investigated retrospectively in a large cohort of the Tyrolean PCa patients, the majority of whom have been diagnosed in an age-adjusted PSA-based screening program for early detection and treatment of PCa.20, 21 We observed an increased frequency of ERG overexpression in younger PCa patients and association with lower serum PSA.

Conclusions
ERG overexpression is significantly more frequent in tumors detected at a younger age and is associated with lower PSA levels in this age group. In tumors detected at an older age, ERG overexpression is significantly associated with a higher TV but not with differences in PSA. ERG overexpression seems to accelerate carcinogenesis and drive prostate tumors to early clinical manifestation and detection but have no effect on tumor progression.

Do not treat it with "alternative medicine"

hard to figure which is the right direction to go in.

The fact that it took a month to get your results would send up a RED FLAG for me about your current physician.

Get busy living, or get busy dying.

Discussion
The optimal management for localized prostate cancer
is controversial. While men with low-risk and selected
intermediate-risk prostate cancer can be managed by
active surveillance, the majority of men with early
prostate cancer are radically treated with either surgery
or radiation therapy. With better patient selection
by defining the biological potential of the cancer and
with improvements in technology to follow these men,
active surveillance will become more widely used. For
low-risk and some intermediate-risk patients, active
surveillance is usually recommended since the cancer
is noninvasive and has an overall survival rate comparable
to other radical treatments.2,3 Nevertheless,
there is a subset of men with early cancer who will
benefit from active treatment; however, they also may
benefit from focal treatment of their localized cancer
without subjecting them to the potential risks and
complications of radical local treatment.