Biomedical subjects

I A Sesterhenn

Publications and source records attributed to I A Sesterhenn.

At least 19 recordsLinked to original sources

PubMed2006

Classification of canine urinary bladder urothelial tumours based on the World Health Organization/International Society of Urological Pathology consensus classification.

One hundred canine urinary bladder urothelial (transitional cell) tumours, including roughly equal numbers of benign and malignant forms, were retrospectively categorized in accordance with the newly described human consensus classification of the World Health Organization/International Society of Urological Pathology (WHO/ISUP). The tumours were reviewed and classified by three veterinary pathologists from Michigan State University and two human pathologists from the Armed Forces Institute of Pathology (AFIP). The current human WHO/ISUP classification system was considered to be readily applicable to the dog. Canine tumours, however, differed from human tumours in that the great majority showed extensive glandular differentiation (or metaplasia) and hyperplastic lesions tended to be more florid than those seen in human beings. The various diagnoses and grades assigned to the tumours were highly consistent between all reviewing pathologists. This paper presents the salient features of the new WHO and ISUP consensus classification and provides illustrations of the various tumour types that were directly applicable to the dog.

Animals↗

PubMed2006

Quantitative expression profile of PSGR in prostate cancer.

PSGR is a novel member of the G-protein-coupled olfactory receptor family. Our initial report showed predominant expression of the PSGR in human prostate gland and significant alterations of PSGR expression in primary prostate cancer (CaP) specimens. The aim of this study was to provide in-depth evaluations of the expression profile of PSGR in prostatic epithelial cells of CaP patients and to evaluate the association of PSGR expression characteristics with clinico-pathologic features. In total, 220 RNA specimens, from laser capture microdissected paired benign and malignant prostatic epithelial cells of 110 CaP patients, were analyzed for PSGR expression by quantitative real-time PCR. The differential expression of PSGR between the prostatic epithelial cells of malignant and benign glands was statistically significant (P<0.0001). Comparison of PSGR expression between paired benign and tumor cells revealed prostate tumor cell-specific overexpression in 67.2% of tumor specimens (74 of 110), decreased expression in 20.9% of tumor specimens (23 of 110) and no difference of PSGR expression between tumor and normal cells in 11.8% of specimens (13 of 110). In representative cases, PSGR expression patterns were independently confirmed by in situ RNA hybridization. The PSGR overexpression associated with higher percentage of pathologic stage, pT3, and a higher level of preoperative serum PSA. CaP cells of African-American CaP patients exhibited about two-fold increase of PSGR expression in comparison to the Caucasian American CaP patients. Strikingly high-percentage CaP cells overexpress PSGR warrants further studies of PSGR expression alterations to define subsets of CaPs.

Black or African American↗

PubMed2005

Risk of prostate cancer and family history of cancer: a population-based study in China.

We evaluated prostate cancer risk and family history of cancers using data from a case-control study in China. Cancer information among first-degree relatives was collected from 709 subjects (238 cases and 471 controls). None of the subjects reported a family history of prostate cancer. However, excess prostate cancer risk was associated with a family history of any cancer (OR = 1.79, 95% CI: 1.21-2.63) and esophageal cancer (OR = 2.39, 95% CI: 1.15-5.00). Nonsignificant risk was seen for family history of cancers of the stomach, lung, and female breast. Our results did not confirm the familial tendency toward prostate cancer but other cancers prevalent in China appeared to be aggregate, particularly esophageal cancer. Larger studies are needed to confirm these findings, and to clarify the genetic and lifestyle factors that may be involved.

Aged↗

PubMed2003

p53 Immunostaining guided laser capture microdissection (p53-LCM) defines the presence of p53 gene mutations in focal regions of primary prostate cancer positive for p53 protein.

OBJECTIVES: A wide range of p53 mutations (5-65%), detected by various methods, has been reported in primary prostate cancers (CaP). IHC staining of radical prostatectomy specimens shows marked heterogeneity of focally distributed p53-positive cells. However, a significant relationship between the focal staining of p53 and cancer recurrence after radical prostatectomy has been noted. Increased frequency of p53 mutations has been generally observed in advanced stage CaP and metastatic prostate cancer cell lines. The significance of focal p53 immunostaining in primary CaP remains uncertain with respect to the p53 gene mutation or tumor progression. The goal of this study was to evaluate p53 gene mutations in focal regions of primary prostate cancers positive by p53 immunostaining. METHODS: Whole-mount prostates from men with clinically organ-confined prostate cancer were immunostained for p53 protein. Laser capture microdissection (LCM) was used to harvest p53 positive cells from areas of tumor and prostatic intraepithelial neoplasia and benign gland. DNA from microdissected cells were amplified for p53 exons 5-8 by polymerase chain reaction (PCR) and analyzed for mutations by single strand conformation polymorphism and DNA sequencing. Mutation analysis of the p53 gene exons 5-8 was performed in the p53 immunostaining positive focal regions (1+ to 4+) of whole-mount prostate sections from 16 patients. RESULTS: Of 16 patients with p53 IHC positive tumors, 11 (69%) had p53 gene mutations as determined by DNA sequence analysis. However, randomly microdissected tumor cells from 4 of 18 patients (22%) negative for p53 IHC also demonstrated mutations in the p53 gene. A significant fraction of prostate tumors with focally positive immunostaining for p53 have been confirmed to contain mutations in the p53 gene. CONCLUSIONS: p53 immunostaining guided LCM combined with DNA-based analyses emphasizes the presence of focal p53 mutations in primary prostate cancers and underscores the significance of previous observations showing a correlation between focal p53 immunostaining in primary CaP and cancer recurrence after radical prostatectomy.

Base Sequence↗

PubMed2002

Investigating the distribution of prostate cancer using three-dimensional computer simulation.

The objective of this work was to investigate the distribution of prostate cancer using three-dimensional (3-D) computer simulation. Two hundred and eighty-one 3-D computer prostate models were constructed from radical prostatectomy specimens. An algorithm was developed which divided each model into 24 symmetrical regions, and it then detected the presence of tumor within an individual region. The distribution rate of prostate cancer was assessed within each region of all 281 prostate models, and the difference between the rates was statistically analyzed using Mantel-Haenszel methodology. There was a statistically significant higher distribution rate of cancer in the posterior half (57.2%) compared to the anterior half ( 40.5%; P=0.001). The base regions (36.8%) had a statistically significant lower distribution rate than either the mid regions (56.3%; P=0.001) or the apical regions (53.5%; P=0.001). The mid regions did have a statistically significant higher distribution rate compared to the apical regions (P=0.032). There was no statistically significant difference between the distribution rate on the left half (48.5%) compared to that on the right half (49.2%; P=0.494). The spatial distribution of prostate cancer can be analyzed using 3-D computer prostate models. The results illustrate that prostate cancer is least commonly located in the anterior half and base regions of the prostate. Through an analysis of the spatial distribution of prostate cancer, we believe that new optimal biopsy strategies and techniques can be developed.

Biopsy↗

PubMed2002

Complete embedding and close step-sectioning of radical prostatectomy specimens both increase detection of extra-prostatic extension, and correlate with increased disease-free survival by stage of prostate cancer patients.

The objectives of this work were to evaluate the efficacy of controlled close step-sectioned and whole-mounted radical prostatectomy specimen processing in prediction of clinical outcome as compared to the traditional processing techniques. Two-hundred and forty nine radical prostatectomy (RP) specimens were whole-mounted and close step-sectioned at caliper-measured 2.2-2.3 mm intervals. A group of 682 radical prostatectomy specimens were partially sampled as control. The RPs were performed during 1993-1999 with a mean follow-up of 29.3 months, pretreatment PSA of 0.1-40, and biopsy Gleason sums of 5-8. Disease-free survival based on biochemical or clinical recurrence and secondary intervention were computed using a Kaplan-Meier analysis. There were no significant differences in age at diagnosis, age at surgery, PSA at diagnosis, or biopsy Gleason between the two groups (P<0.05). Compared with the non-close step-sectioned group, the close step-sectioned group showed higher detection rates of extra-prostatic extension (215 (34.1%) vs, 128 (55.4%), P<0.01), and seminal vesicle invasion (50 (7.6%) vs 35 (14.7%), P<0.01). The close step-sectioned group correlated with greater 3-y disease-free survival in organ-confined (P<0.01) and specimen-confined (P<0.01) cases, over the non-uniform group. The close step-sectioned group showed significantly higher disease-free survival for cases with seminal vesicle invasion (P=0.046). No significant difference in disease-free survival was found for the positive margin group (P=0.39) between the close step-sectioned and non-uniform groups. The close step-sectioned technique correlates with increased disease-free survival rates for organ and specimen confined cases, possibly due to higher detection rates of extra-prostatic extension and seminal vesicle invasion. Close step-sectioning provides better assurance of organ-confined disease, resulting in enhanced prediction of outcome by pathological (TNM) stage.

Adult↗

PubMed2001

A novel human cancer culture model for the study of prostate cancer.

Research into molecular and genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro models of prostate tumors representing primary tumors. We have successfully established an immortalized human prostate epithelial (HPE) cell culture derived from a primary tumor with telomerase. The actively proliferating early passaged RC-58T cells were transduced through infection with a retrovirus vector expressing the human telomerase catalytic subunit (hTERT). A high level of telomerase was detected in RC-58T/hTERT cells but not RC-58T cells. RC-58T/hTERT cells are currently growing well at passage 50, whereas RC-58T cells senesced at passage 7. RC-58T/hTERT cells exhibit transformed morphology. More importantly, these immortalized cells showed anchorage-independent growth as they formed colonies in soft agar and grew above the agar layer. Expression of androgen-regulated prostate specific gene NKX3.1 and epithelial specific cytokeratin 8 (CK8) but not prostate specific antigen (PSA) and androgen receptor was detected in RC-58T/hTERT cells. Prostate stem cell antigen (PSCA) and p16 were also expressed in this cell line. RC-58T/hTERT cells showed growth inhibition when exposed to retinoic acid and transforming growth factor (TGF)-beta1 known potent inhibitors of prostate epithelial cell growth. A number of chromosome alterations were observed including the loss of chromosomes Y, 3p, 10p, 17p, 18q and the gain of chromosomes 16 and 20. These results demonstrate that this primary tumor-derived HPE cell line retained its transformed phenotypes and should allow studies to elucidate molecular and genetic alterations involved in prostate cancer. This is the first documented case of an established human prostate cancer cell line from a primary tumor of a prostate cancer patient with telomerase.

Agar↗

PubMed2001

Improvements in pathologic staging for African-American men undergoing radical retropubic prostatectomy during the prostate specific antigen era: implications for screening a high-risk group for prostate carcinoma.

BACKGROUND: The objective was to compare the changes in pathologic and clinical data over time for African-American (AA) and white men with prostate carcinoma undergoing radical prostatectomy in an attempt to determine the early impact of prostate specific antigen (PSA). METHODS: Data from 195 AA and 587 white men who underwent radical prostatectomy from 1988 to 1999 in an equal access, tertiary, military medical facility were collected. Statistical analysis was used to determine the significance of the changes in the rates of extracapsular extension (ECE), positive margins, pretreatment PSA levels, and age at the time of surgery for each race over time. RESULTS: Comparing 1988-99 results, the authors found that the percentage of AA men with ECE decreased from 100% to 34.8% (P = 0.007), and for white men from 56.9% to 43.2% (P = 0.269). The percentage of AA men with positive margins decreased from 100% to 26.1% (P < 0.0001), and for white men from 41.2% to 27.0% (P = 0.021). Mean age at surgery decreased from 66.6 to 59.9 years for AA men (P < 0.001) and from 65.9 to 61.1 years for white men (P < 0.001). Also, PSA levels decreased from 10.1 to 6.6 ng/dL for white men (P < 0.001) and from 16.5 to 6.5 ng/dL for AA men (P < 0.001). CONCLUSIONS: The authors believe that the decrease in ECE and positive margins in AA men is primarily because of PSA testing, coupled with improved public awareness and equal access to care. It appears reasonable to recommend PSA testing in AA men, who have historically experienced poor outcomes from prostate carcinoma.

Adult↗

PubMed2001

Vitamin D receptor gene polymorphisms, insulin-like growth factors, and prostate cancer risk: a population-based case-control study in China.

Operating through the vitamin D receptor (VDR), vitamin D inhibits prostate cancer growth and increases insulin-like growth factor binding protein (IGFBP) expression, suggesting that the vitamin D and insulin-like growth factor (IGF) regulatory systems may operate together to affect prostate cancer. Among 191 newly diagnosed prostate cancer cases and 304 randomly selected population controls in Shanghai, China, we found no significant association between the BsmI or FokI VDR gene polymorphisms and prostate cancer risk. However, we found that among men with the ff FokI genotype, those in the highest tertile of plasma IGFBP-3 had a decreased risk versus those in the lowest tertile (odds ratio, 0.14; 95% confidence interval, 0.04-0.56; P(trend) < 0.01), whereas among men with the FF and Ff genotypes, IGFBP-3 was not associated with risk. Similarly, IGFBP-1 was inversely associated with prostate cancer risk only among men with the ff FokI genotype (odds ratio, 0.25; 95% confidence interval, 0.07-0.85; P(trend) = 0.02). No such FokI genotype-specific effects were observed for IGF-I or IGF-II. Our findings in a low-risk population suggest that the IGF and vitamin D regulatory systems may interact to affect prostate cancer risk. Larger studies are needed to confirm these findings and clarify the underlying mechanisms.

Adolescent↗

PubMed2001

Interobserver reproducibility of Gleason grading of prostatic carcinoma: urologic pathologists.

Gleason grading is now the most widely used grading system for prostatic carcinoma in the United States. However, there are only a few studies of the interobserver reproducibility of this system, and no extensive study of interobserver reproducibility among a large number of experienced urologic pathologists exists. Forty-six needle biopsies containing prostatic carcinoma were assigned Gleason scores by 10 urologic pathologists. The overall weighted kappa coefficient kappa(w) for Gleason score for each of the urologic pathologists compared with each of the remaining urologic pathologists ranged from 0.56 to 0.70, all but one being at least 0.60 (substantial agreement). The overall kappa coefficient kappa for each pathologist compared with the others for Gleason score groups 2-4, 5-6, 7, and 8-10 ranged from 0.47 to 0.64 (moderate-substantial agreement), only one less than 0.50. At least 70% of the urologic pathologists agreed on the Gleason grade group (2-4, 5-6, 7, 8-10) in 38 ("consensus" cases) of the 46 cases. The 8 "nonconsensus" cases included low-grade tumors, tumors with small cribriform proliferations, and tumors whose histology was on the border between Gleason patterns. Interobserver reproducibility of Gleason grading among urologic pathologists is in an acceptable range.

Humans↗

PubMed2001

Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China.

BACKGROUND: Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. METHODS: In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. RESULTS: Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. CONCLUSIONS: Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

Adult↗

PubMed2001

Insulin-like growth factors and prostate cancer: a population-based case-control study in China.

Insulin-like growth factors (IGFs) have potent mitogenic and antiapoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity and other mechanisms, IGF-binding proteins (IGFBPs) also have growth-regulatory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP-3 are also associated with prostate cancer in a low-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected population controls in Shanghai, China. Relative to the lowest quartile of IGF-I levels, men in the highest quartile had a 2.6-fold higher prostate cancer risk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence interval (95% CI) = 1.19-5.79; P(trend) = 0.01]. In contrast, men in the highest quartile of IGFBP-3 levels had a 46% decreased risk relative to the lowest quartile (OR = 0.54; 95% CI = 0.26-1.15; P(trend) = 0.08). A similar but less distinct result was observed for IGFBP-1 (OR = 0.60; 95% CI = 0.31-1.17; P(trend) = 0.25). Men in the highest quartile for the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) had a 2.5-fold higher risk compared with the lowest quartile (OR = 2.51; 95% CI = 1.32-4.75, P(trend) < 0.001). These associations were more pronounced after adjustment for serum 5alpha-androstane-3alpha,17beta-diol glucuronide and sex hormone-binding globulin levels. There was no significant association with IGF-II levels. Our findings in a low-risk population provide evidence that IGF-I, IGFBP-3, and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to elucidate carcinogenic mechanisms.

Aged↗

PubMed2001

Polymorphic markers in the SRD5A2 gene and prostate cancer risk: a population-based case-control study.

It has been suggested that the activity of the steroid 5alpha-reductase type II enzyme (encoded by the SRD5A2 gene) may be associated with prostate cancer risk and that population differences in this enzyme's activity may account for part of the substantial racial/ethnic disparity in prostate cancer risk. To provide etiological clues, we evaluated the relationships of four polymorphic markers in the SRD5A2 gene, specifically, A49T (a substitution of threonine for alanine at codon 49), V89L (a substitution of leucine for valine at codon 89), R227Q (a substitution of glutamine for arginine at codon 227), and a (TA)n dinucleotide repeat, with prostate cancer risk in a population-based case-control study in China, a population with the lowest reported prostate cancer incidence rate in the world. Genotypes of these four markers were determined from genomic DNA of 191 incident cases of prostate cancer and 304 healthy controls using PCR-based assays, and serum androgen levels were measured in relation to these genotypes. All study subjects had the wild-type AA genotype of the A49T marker, and 99% had the RR genotype of the R227Q marker. For the V89L marker, prevalences of the LL, VV, and VL genotypes among controls were 35%, 21%, and 45%, respectively. Compared with men with the VV genotype, those with the LL genotype had a statistically nonsignificant 12% reduced risk (odds ratio = 0.88, 95% confidence interval, 0.53-1.47). In addition, men with the LL genotype had significantly higher serum levels of testosterone and significantly lower serum levels of 5alpha-androstane-3alpha,17beta-diol glucuronide than men with other genotypes. Men heterozygous for the (TA)0 allele of the (TA)n marker had a modest, statistically nonsignificant risk reduction (odds ratio = 0.67; 95% confidence interval, 0.39-1.12) compared with men homozygous for the (TA)0 allele, along with significantly higher serum dihydrotestosterone levels. The observed V89L genotype prevalences and the association between V89L genotypes and serum androgen levels support the hypothesis that genotypes associated with lower levels of 5alpha-reductase activity are more common in low-risk populations. Although we found no statistically significant associations of these SRD5A2 polymorphisms with prostate cancer risk, a small effect of these markers cannot be ruled out because of the rarity of certain marker genotypes. Larger studies are needed to further clarify the role of these markers and to elucidate whether genetic diversity of the SRD5A2 gene, alone or in combination with other susceptibility genes, can help explain the large racial/ethnic differences in prostate cancer risk.

Adult↗

PubMed2000

PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer.

PSGR, a new prostate tissue-specific gene with homology to the G protein-coupled odorant receptor gene family, has been identified. Here we report the characteristics of the predicted protein sequence of PSGR and its prostate tissue specificity and expression profile in human prostate cancer and matched normal tissues. Using multiple tissue Northern blots from over 50 different tissues, PSGR expression was restricted to human prostate tissues. Paired normal and tumor specimens from 52 primary prostate cancers, obtained by laser capture microdissection or manual microdissection, were analyzed for PSGR expression by semiquantitative and real-time PCR assays. The differential expression of PSGR between normal and tumor tissues was highly significant (P < 0.001), and 32 of 52 (62%) matched prostate specimens exhibited tumor-associated overexpression of PSGR. Of note, there was very little or no expression of PSGR in many normal specimens in comparison with the generally high expression of PSGR seen in matched tumor specimens. In situ hybridization assays showed restricted PSGR expression in the epithelial cells of the normal and tumor tissue sections. Restricted expression of PSGR in prostatic epithelial cells, overexpression of the PSGR in a significant percentage of prostate cancers, and the predicted protein sequence of PSGR with seven transmembrane domains provide a foundation for future studies evaluating the potential of PSGR as a prostate cancer gene expression marker and the utility of PSGR protein as a novel target for developing immunotherapeutic strategies for prostate cancer.

Amino Acid Sequence↗

PubMed2000

PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer.

A prostate-specific gene, PCGEM1, was identified by differential display analysis of paired normal and prostate cancer tissues. Multiple tissue Northern blot analysis revealed that PCGEM1 was expressed exclusively in human prostate tissue. Analysis of PCGEM1 expression in matched normal and primary tumor specimens revealed tumor-associated overexpression in 84% of patients with prostate cancer by in situ hybridization assay and in 56% of patients by reverse transcription-PCR assay. Among various prostate cancer cell lines analyzed, PCGEM1 expression was detected only in the androgen receptor-positive cell line LNCaP. Extensive DNA sequence analysis of the PCGEM1 cDNA and genomic DNA revealed that PCGEM1 lacks protein-coding capacity and suggests that it may belong to an emerging class of noncoding RNAs, also called "riboregulators." The PCGEM1 locus was mapped to chromosome 2q32. Taken together, the remarkable prostate-tissue specificity and androgen-dependent expression of PCGEM1 as well as its elevated expression in a significant percentage of tumor tissues suggest specific functions of PCGEM1 in the biology and tumorigenesis of the prostate gland.

Androgens↗

PubMed2000

Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China.

The length of the polymorphic CAG trinucleotide repeat in the polyglutamine region of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Because increased androgenic activity has been linked to prostate cancer and because an ethnic variation exists in the CAG repeat length, this polymorphism has been suggested to explain part of the substantial racial difference in prostate cancer risk. We conducted a population-based case-control study in China to investigate whether CAG and other polymorphisms of the AR gene are associated with clinically significant prostate cancer in this low-risk population. Genomic DNA from 190 prostate cancer patients and 304 healthy controls was used for direct sequencing to evaluate the relationship of CAG and GGN (polyglycine) repeat length in the AR gene. Relative to western men, our study subjects had a longer CAG repeat length, with a median of 23 and only 10% of the subjects having a CAG repeat length shorter than 20. Men with a CAG repeat length shorter than 23 (median length) had a 65% increased risk of prostate cancer (odds ratio, 1.65; 95% confidence interval, 1.14-2.39), compared with men with a CAG repeat length of 23 or longer. For the GGN tract (GGT3GGG1GGT2GGCn), based on the sequencing results from 481 samples, we are the first to show that although GGC regions in the polyglycine tract are highly variable, there are no mutations or polymorphisms in the GGT and GGG regions. More than 72% of the subjects had a GGN repeat length of 23, and those with a GGN repeat length shorter than 23 had a 12% increased risk of prostate cancer (95% confidence interval, 0.71-1.78), compared with those with > or = 23 GGN repeats. Our study not only confirms that Chinese men do have a longer CAG repeat length than western men but also represents the first population-based study to show that even in a very low-risk population, a shorter CAG repeat length confers a higher risk of clinically significant prostate cancer. These results imply that CAG repeat length can potentially serve as a useful marker to identify a subset of individuals at higher risk of developing clinically significant prostate cancer. Larger studies are needed to evaluate the combined effect of CAG and GGN repeats. Because of the significance of AR in prostate cancer, investigation of factors that interact with the polyglutamine region of the AR gene to alter AR function and modulate prostate cancer risk is an important area for future research.

Aged↗

PubMed2000

A novel androgen-regulated gene, PMEPA1, located on chromosome 20q13 exhibits high level expression in prostate.

Biologic effects of androgen on target cells are mediated in part by transcriptional regulation of androgen-regulated genes (ARGs) by androgen receptor. Using serial analysis of gene expression (SAGE), we have identified a comprehensive repertoire of ARGs in LNCaP cells. One of the SAGE-derived tags exhibiting homology to an expressed sequence tag was maximally induced in response to synthetic androgen R1881 treatment. The open reading frame of the androgen-induced RNA (PMEPA1) was characterized as a 759-bp nucleotide sequence coding for a 252-amino-acid protein. The analysis of PMEPA1 protein sequence indicated the existence of a type Ib transmembrane domain between residues 9 and 25. Analysis of multiple-tissue Northern blots revealed the highest level of PMEPA1 expression in prostate tissue. PMEPA1 expression was predominately detected in glandular epithelial cells of prostate by in situ hybridization analysis. The expression of PMEPA1 in LNCaP cells was induced by androgen in a time- and dose-specific manner. Evaluation of PMEPA1 expression in androgen-dependent/independent tumors of the CWR22 xenograft model revealed that PMEPA1 was overexpressed in three of four androgen-independent tumor tissues. These observations define PMEPA1 as a novel androgen-regulated gene exhibiting abundant expression in prostate tissue. The increased expression of PMEPA1 in relapsed tumors of the CWR22 model suggests activation of androgen signaling in hormone refractory disease. PMEPA1, along with other highly androgen-induced prostate-specific genes, has potential to serve as an androgen signaling read-out biomarker in prostate tissue.

Androgens↗

PubMed2000

Lateral biopsies added to the traditional sextant prostate biopsy pattern increases the detection rate of prostate cancer.

Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error and data based upon whole-mounted step-sectioned radical prostatectomy specimens using a three-dimensional computer-assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. The simulated 10-core biopsy pattern (traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland) was shown to be superior to the traditional sextant biopsy. The objective of this pilot study was to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in patients. We reviewed data on 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3%(19/35) were diagnosed by the sextant biopsy only. The 10-core pattern resulted in an additional 45.7%(16/35) of patients being diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. In conclusion, biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Prostate Cancer and Prostatic Diseases (2000) 3, 43-46

Journal Article↗