Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression.

Background: The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression.

Methods: Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression.

Results: The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells.

Significance of prostate cancer missed on needle biopsy tools for retrieving missed cancer.

Background: Prostate needle biopsy (PNB) is required for the diagnosis of prostate cancer (PCa), but little is known about the frequency and clinical implication of false-negative results.

Objective: To investigate the incidence and clinical impact of minute PCa missed on routine haematoxylin and eosin (H&E) slides, but retrieved by α-methylacyl-CoA-racemase (AMACR) immunohistochemistry.

Methods: AMACR immunohistochemistry was used to detect PCa missed on H&E slides in a series of consecutive 1,672 PNB including 1,003 patients without evidence of PCa, and 669 patients with PCa meeting pathological criteria for active surveillance (PCAS) under current clinical investigation, including Gleason score ≤7 (3 + 4), <33% of biopsies involved by cancer, <50% of any core involved by cancer.

Reliable identification of transition zone prostatic adenocarcinoma in preoperative needle core biopsy.

Prostatic adenocarcinomas arising within the transition zone (Tz) are distinct from peripheral zone (Pz) tumors as regards biological aggression and mechanism of extraprostatic extension. Reliable biopsy identification of Tz tumors would allow targeted surgical approaches more likely to preserve erectile function without compromising surgical margins. Previous studies have demonstrated the presence of eosinophilic cytoplasmic granules (prostate secretory granules, or PSGs) after glutaraldehye fixation, with apparent depletion in neoplasia.

Intraductal carcinoma of the prostate: precursor or aggressive phenotype of prostate cancer?

Background: Although the term "intraductal carcinoma of the prostate" (IDC-P) was introduced almost 40 years ago, there is still the lack of appreciation that this entity represents a clinically aggressive disease that continues to be misreported under the diagnostic category of high grade prostatic intraepithelial neoplasia (HGPIN).

Methods: Recent data obtained from histological, molecular, and clinical studies were reviewed to demonstrate that IDC-P significantly differs from HGPIN, and has a major impact in terms of diagnosis, prognosis and therapy of prostate cancer (PCa).

Results: HGPIN is the only accepted precursor of PCa.

Factors implicated in radiation therapy failure and radiosensitization of prostate cancer.

Tissue markers may be helpful in enhancing prediction of radiation therapy (RT) failure of prostate cancer (PCa). Among the various biomarkers tested in Phase III randomized trials conducted by the Radiation Therapy Oncology Group, p16, Ki-67, MDM2, COX-2, and PKA yielded the most robust data in predicting RT failure. Other pathways involved in RT failure are also implicated in the development of castration-resistant PCa, including the hypersensitive androgen receptor, EGFR, VEGF-R, and PI3K/Akt.

From pathogenesis to prevention of castration resistant prostate cancer.

Background: Significant progress in understanding the molecular basis of castration resistant prostate cancer (CRPCa) has been achieved in recent years. Despite this progress, CRPCa still remains a lethal disease. Early detection and prevention of CRPCa may provide a new strategy to improve survival of patients diagnosed with PCa at risk to fail standard androgen deprivation therapy (ADT).

The evolving role of oestrogens and their receptors in the development and progression of prostate cancer.

Context: Oestrogens were proven effective in the hormonal treatment of advanced prostate cancer (PCa) >60 yr ago and are still used as second-line hormonal therapy. Paradoxically, oestrogens might also be involved in the development and progression of PCa.

Objective: To examine mechanisms of how oestrogens may affect prostate carcinogenesis and tumour progression.

A proposal on the identification, histologic reporting, and implications of intraductal prostatic carcinoma.

Context: Prostatic adenocarcinoma growing within acinar-ductal spaces (intraductal carcinoma) in contrast to high-grade prostatic intraepithelial neoplasia (HG-PIN) impacts negatively on patient outcome. There is currently no generally accepted definition of this lesion nor is it classified in the current prostate cancer grading system (Gleason).

Objective: To define intraductal carcinoma of the prostate (IDC-P) with major and minor diagnostic criteria that clearly separate it from HG-PIN.

[Implications of estrogens and their receptors for the development and progression of prostate cancer].

The recent discovery of the estrogen receptors alpha and beta (ERalpha, ERbeta) and the progesterone receptor (PR) in human prostate tissue offers new insights into the role of estrogens and their receptors in prostate cancer development and tumor progression. The differentiation compartment of the prostatic epithelium (secretory luminal cells) expresses high levels of ERbeta, while the ERalpha is restricted to the proliferation compartment (basal cells). In high grade prostatic intraepithelial neoplasia (HGPIN), ERalpha gene expression extends to luminal cells and thus may mediate cancerogenic effects of estrogens on the dysplastic epithelium.

[Gleason grading: diagnostic criteria and clinical implications].

Prostate cancer offers a wide spectrum ranging from clinically insignificant to aggressive and fatal disease. The Gleason grade is a powerful prognostic indicator and does influence treatment decision. Educational programs and websites are currently available to improve reproducibility and reliability of Gleason grading.

[Prognostic factors in prostate cancer].

Since several therapeutic options are currently available for clinically organ-confined prostate cancer, morphological parameters have rapidly emerged as prognostic factors to stratify patients into different therapeutic modalities. In addition to the PSA value, pathologic stage, as defined by the TNM system, Gleason grade and the surgical margin status, other markers have prognostic implications. This includes the percent pattern 4/5 cancer, tumor volume, intraductal spread, large volume perineural invasion and molecular markers.

[Differential diagnosis of prostate cancer: impact of pattern analysis and immunohistochemistry].

Prostate cancer offers a wide range of growth patterns depicted in the classical Gleason diagram. For each Gleason pattern exist a number of benign and malignant mimickers that can simulate prostatic adenocarcinoma. In the present review, the use of immunohistochemical markers is discussed with emphasis to a pattern-based approach to differential diagnosis in prostate pathology.

[Neuroendocrine differentiation in prostate cancer: an unrecognized and therapy resistant phenotype].

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies but usually escapes pathological and clinical detection. The present review focuses on biological properties of NE tumor cells making them resistant to androgen deprivation and radiation therapy. Recent data have shown that NE prostate cancer cells (as defined by the most commonly used endocrine marker chromogranin A) are arrested in the G0-phase of the cell cycle and do not undergo apoptosis.

Simultaneous tumour-like, atypical basal cell hyperplasia and acinar adenocarcinoma of the prostate: a comparative morphological and genetic approach.

Basal cell tumours of the prostatic gland are rare, and the classification is difficult. In the present case report, a large, tumour-like proliferation of atypical basaloid cells was found incidentally in a prostatectomy specimen that otherwise contained a conventional acinar adenocarcinoma. The basaloid cells displayed a solid or adenoid-cystic growth pattern and strongly expressed high-molecular-weight cytokeratins and bcl-2.

TRPV6 and prostate cancer: cancer growth beyond the prostate correlates with increased TRPV6 Ca2+ channel expression.

Life expectancy for patients suffering from prostate cancer is inversely correlated with the degree of extraprostatic metastasis. In order to find pharmacological tools to treat this aggressive growth it is important to define targets whose expression not only correlates with the malignancy of the cancerous cells, but that are also amenable to pharmacological intervention. In this review, we would like to focus on the potential role of a distinct class of ion channels that may be involved in this process.

[Neuroendocrine differentiation in prostate cancer. An unrecognized and therapy-resistant phenotype].

Neuroendocrine (NE) differentiation frequently occurs in common prostatic malignancies and has attracted increasing attention in contemporary prostate cancer research. This particular phenotype, however, usually escapes pathological and clinical detection in routine practice. The present review focuses on the biological properties of NE tumor cells that make them resistant to androgen deprivation and radiation therapy.

[New insights into the role of estogens and their receptors in prostate cancer].

The present review gives a survey on the differential expression of estrogen receptors alpha and beta (ERalpha, ERbeta) and the progesterone receptor (PR) in human prostate tissue and discusses their potential implications for normal and abnormal prostatic growth. The differentiation compartment of the prostatic epithelium (secretory luminal cells) expresses high levels of ERbeta, while the ERalpha is restricted to the proliferation compartment (basal cells). In high-grade prostatic intraepithelial neoplasia (HGPIN), ERalpha gene expression extends to luminal cells and thus may mediate cancerogenic effects of estrogens on the dysplastic epithelium.

Expression of the Ca2+-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression.

Members of the TRP superfamily of cation channels have homeostatic and regulatory functions in cells and changes in their expression may contribute to malignant growth. Previously, we have demonstrated that the gene of the Ca2+-selective cation channel CaT-L or TRPV6 is not expressed in benign prostate tissues including benign prostate hyperplasia, but is upregulated in prostate cancer. Here, we report on the differential expression of TRPV6 mRNA in prostate tissue obtained from 140 patients with prostate cancer.

Telomerase activity and telomerase subunit gene expression levels are not related in prostate cancer: a real-time quantification and in situ hybridization study.

Because the mechanisms of telomerase activation in prostate cancer are mainly unknown, we investigated the relationships between telomerase activity and expression levels of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA in benign and malignant alterations of the human prostate gland. Using the LightCycler technology, hTERT mRNA expression was quantified in 46 radical prostatectomy and 10 benign prostatic hyperplasia (BPH) cases; hTR expression was quantified in a subset of these tissue samples. Telomerase activity was measured using a quantitative telomeric repeat amplification protocol ELISA assay.

Differential expression of the estrogen receptor beta (ERbeta) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma.

Background: Estrogen signaling mediated by the estrogen receptor beta (ERbeta) has potential implications in normal and abnormal prostate growth. Few studies have addressed this issue in human prostate tissue leaving conflicting results on the immunolocalization of the ERbeta in benign and neoplastic lesions.

Methods: Using a new monoclonal antibody, the current study reports on the differential expression of the ERbeta in tissue sections from 132 patients with prostate cancer.

Apoptosis resistance of neuroendocrine phenotypes in prostatic adenocarcinoma.

Background: Neuroendocrine (NE) differentiation has been implicated in prostate cancer progression and hormone therapy failure. It has been shown that prostate cancer cells with NE features lack proliferation activity in vitro and in vivo. The current study reports on the apoptotic status of NE phenotypes in human prostate cancer.

[Solid-pseudopapillary tumor of the pancreas in a 9-year-old girl].

Solid-pseudopapillary tumor of the pancreas constitutes a very rare benign or low-grade malignant lesion occurring most commonly in young women and girls. It was first described by Frantz. Local infiltration, distant metastasis and recurrence are very rare.

Neuroendocrine differentiation in human prostate cancer. Morphogenesis, proliferation and androgen receptor status.

Background: The frequent occurrence of neuroendocrine (NE) differentiation in common prostatic malignancies has attracted increasing attention in contemporary prostate cancer research.

Methods: The present review focuses on growth properties and the androgen receptor (AR) status of NE phenotypes, and discusses their morphogenetic origin in benign and malignant prostate tissue.

Results: Recent data have documented a phenotype link between NE cells and other cell lineages encountered in benign and malignant prostate tissue.

Progesterone receptor expression in human prostate cancer: correlation with tumor progression.

Background: The recent discovery of the classical estrogen receptor alpha (ERalpha) in metastatic and recurrent prostatic adenocarcinoma suggests that estrogens are implicated in prostate cancer progression.

Methods: To get more insight into estrogen signaling in prostate cancer tissue, the current study has examined the immunoprofile of the estrogen-inducible progesterone receptor (PR), and evaluated its relation to ERalpha gene expression.

Results: In primary tumors, the PR was detectable in 36% of primary Gleason grade 3 (5 of 14 cases), 33% of primary Gleason grade 4 (5 of 15 cases), and in 58% of primary Gleason grade 5 tumors (7 of 12 cases).