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D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 199 records · Page 11Linked to original sources
PubMed1997

Detection of chromosomal anomalies and c-myc gene amplification in the cribriform pattern of prostatic intraepithelial neoplasia and carcinoma by fluorescence in situ hybridization.

Grading of the cribriform pattern of prostate cancer is controversial, and the genetic changes are largely unknown. Furthermore, the pathogenetic relationship between the cribriform pattern of high-grade prostatic intraepithelial neoplasia (PIN) and cribriform carcinoma is poorly understood. We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y and a region-specific probe for c-myc to evaluate genetic changes in matched foci of high-grade PIN (48 foci) and prostatic carcinoma (71 foci) in 25 whole-mount radical prostatectomy specimens from patients with metastatic cancer. These cases included 10 foci of cribriform PIN and 10 foci of cribriform cancer. Numeric chromosomal anomalies were found in 67 and 68% of the high-grade PIN and carcinoma foci, respectively. Extra copies of the c-myc gene were identified in 52 and 44% of the high-grade PIN and carcinoma foci, respectively. The cribriform pattern of cancer had a higher percentage of foci with gain of chromosomes 7, 12, and Y, loss of chromosome 8, and extra copies of c-myc gene than other Gleason Primary Patterns 3 and 4; there was no difference, however, for all paired comparisons of genetic changes between the cribriform pattern of cancer and Gleason Primary Pattern 5 cancer. Cribriform PIN and cribriform cancer generally exhibited similar anomalies, although the percentage of foci with gain of chromosomes 10 and 12 was higher in cribriform cancer. Our results indicate that the cribriform pattern of prostate cancer shares genetic changes with Gleason Primary Pattern 5 and that both contain more genetic changes than the cribriform pattern of PIN. These findings suggest that the cribriform pattern of prostate cancer has biologic similarity with Gleason Pattern 5 carcinoma and that the cribriform pattern of PIN is closely associated with the cribriform pattern of prostatic carcinoma.

Adenocarcinoma↗
PubMed1996

Correlation of pretherapy prostate cancer characteristics with seminal vesicle invasion in radical prostatectomy specimens.

PURPOSE: This study was conducted to identify pretherapy factors associated with seminal vesicle invasion (SVI) in patients with localized carcinoma of the prostate (CaP), and to develop a model that would allow estimation of the likelihood for SVI at the time of initial diagnosis. METHODS AND MATERIALS: Between January 1988 and December 1993, 2959 patients underwent radical retropubic prostatectomy, with or without pelvic lymph node dissection, as initial therapy for clinical Stage T1a-3bN0-XM0 CaP. Preoperative patient and tumor-related characteristics were evaluated for an association with SVI in univariate and multivariate logistic regression analyses. A model was developed and probability plots were constructed to display the estimated likelihood for SVI in the patients with a new diagnosis of localized CaP. RESULTS: Within clinical tumor stage, three groups (T1a-2a, T2b-c, and T3a-b) were observed to have a distinctly different rate of SVI. Gleason primary grades were combined (1-2, 3 and 4-5) because of a similar observation. Univariate analysis identified clinical tumor stage (p < 0.0001), Gleason primary grade (p < 0.0001), and serum prostate-specific antigen level (p < 0.0001) as factors associated with the likelihood for SVI. Multivariate analysis confirmed the independent significance (p = 0.0001) of each of these factors. Patient age (p = 0.16) and history of prior transurethral resection of the prostate (p = 0.82) were not associated with this end point. Probability plots were constructed to display the likelihood of SVI as a function of pretherapy clinical tumor stage, Gleason primary grade, and serum prostate-specific antigen value. CONCLUSION: In the patient with a new diagnosis of localized CaP, clinical tumor stage as determined by digital rectal examination, diagnostic biopsy tumor (Gleason primary) grade, and pretherapy serum prostate-specific antigen value were significant factors for development of a model that estimated the likelihood of SVI. Estimates from this type of model may be of value in the pretherapy diagnostic evaluation of such patients, and may aid in the administration of radiation therapy.

Adult↗
PubMed1996

Allelic imbalance and microsatellite instability in prostatic adenocarcinoma.

Although prostate cancer is one of the most common malignancies of males in Western countries, relatively little is known about the molecular mechanisms involved in tumor initiation and progression. Allelic loss studies have suggested the involvement of multiple tumor suppressor genes (TSGs), but few detailed studies of all chromosomes have been performed. In an effort to localize and identify candidate TSGs, we performed allelic imbalance (AI) studies on 55 prostate cancers, using 135 polymorphic microsatellite markers. For the entire chromosome. AI ranged from a low of 0% on chromosomes 14 and 20 to a high of 71% on chromosome 8. Chromosomal regions demonstrating at least twice the background frequency of AI (ranging from 20 to 69%) included 5q, 6q, 7q, 8p, 13, l6q, l8q, and 21. In addition, AI was examined for association with a number of clinicopathological parameters. AI on chromosomes 7 and 16 were each associated with greater age at diagnosis (P = 0.009 and 0.001, respectively), and AI on chromosomes 10, 16, and 18 was associated with aneuploidy/tetraploidy (P = 0.037, 0.013, and 0.054, respectively). Furthermore, AI on chromosome 5 was associated with a higher pathological stage (P = 0.021) and on chromosome 8 and 16 with a higher Gleason score (P = 0.027 and 0.041, respectively). No tumor exhibited a phenotype of widespread microsatellite instability. These results indicate that there likely exist multiple sites harboring candidate TSG in prostate cancer, some of which may have important clinical implications, and which argue against widespread microsatellite instability.

Adenocarcinoma↗
PubMed1996

Prospective origins of prostate carcinoma. Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia.

BACKGROUND: The search for the precursor of prostatic adenocarcinoma has focused in recent years on two histopathologic findings: high grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). This article describes the diagnostic criteria and clinical significance of PIN and AAH. METHODS AND RESULTS: PIN is the most likely precursor of prostate carcinoma. The continuum that culminates in high grade PIN and early invasive carcinoma is characterized by progressive basal cell layer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, increasing microvessel density, variation in DNA content, and allelic loss. Clinical studies suggest that PIN predates carcinoma by 10 years or more, with low grade PIN first appearing in men in their 30s. AAH is usually found in the transition zone, and shows a weak and inconclusive link to well differentiated adenocarcinoma of the transition zone. CONCLUSIONS: The significance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN coexists with carcinoma in most cases, but retains an intact or fragmented basal cell layer, unlike carcinoma, which lacks a basal cell layer. High grade PIN in biopsies predicts the presence of carcinoma in subsequent biopsies, and PIN provides the highest risk ratio of all known predictive factors. This finding indicates the need for repeat biopsy and follow-up when PIN is identified in a biopsy, especially in patients with an elevated serum prostate specific antigen concentration. PIN also offers promise as an intermediate endpoint in studies of chemoprevention of prostatic carcinoma. Unlike PIN, AAH is weakly linked to carcinoma, and current data indicate that no follow-up is necessary for patients with this finding.

Adenocarcinoma↗
PubMed1996

Analysis of 99 microdissected prostate carcinomas reveals a high frequency of allelic loss on chromosome 8p12-21.

To investigate the possible involvement of a tumor suppressor gene(s) on chromosome 8 in prostatic neoplasms, we performed a comprehensive loss of heterozygosity (LOH) study on 99 tumors from 97 prostate cancer patients. One of the carcinomas was a lymph node metastasis; the other 98 were primary carcinomas. Pure populations of carcinoma cells and normal epithelia were procured by tissue microdissection. Two separate tumor foci were obtained from each of two patients. Microsatellite markers from 25 loci on the short arm and one locus on the long arm of chromosome 8 were used for PCR-based LOH analysis on matched normal and tumor DNA samples. The overall LOH on 8p in this study was 85.9% (85 of 99) of carcinomas. The loss was highest at markers D8S133, D8S136, NEFL, and D8S137 (62,72, 64, and 75%, respectively), which are located at 8p12-21. Seventy-nine of 99 tumors exhibited loss in at least one of these four loci. In contrast, LOH at 8p22 was much lower: 17,18,18, and 19% at D8S549, D8S602, D8S254, and D8S261, respectively, with 25 of 99 tumors showing deletion in one or more of the four loci. All but 5 tumors with deletions in this more distal region had at least one retained locus between the 8p22 deletion and a more proximal region of loss at 8p12-21; 1 tumor had loss at 8p22 but not 8p12-21. This suggests there may be two distinct regions of loss and, therefore, two tumor suppressor genes on this chromosomal arm. The loss on 8p12-21 showed little or no correlation with grade or stage of disease.

Aged↗
PubMed1996

Correlation of pretherapy prostate cancer characteristics with histologic findings from pelvic lymphadenectomy specimens.

PURPOSE: The purpose of this study was to identify pretherapy factors associated with pelvic lymph node involvement (LNI) in patients with localized prostatic carcinoma (CaP), and to develop a model that would allow for estimation of this risk at the time of initial diagnosis. METHODS AND MATERIALS: Between January 1988 and December 1992, 2439 patients with clinical Stage T1a-3cN0-XM0 CaP underwent radical retropubic prostatectomy and bilateral pelvic lymph node dissection as sole initial therapy at a single medical institution. Preoperative factors were evaluated for their association with pelvic LNI in univariate and multivariate logistic regression analysis. A model was developed that incorporated independent predictive variables, and probability plots were generated to estimate the likelihood of pelvic LNI in the patient with a new diagnosis of localized CaP. RESULTS: Within clinical tumor stage, three groups (Tla-2a, T2b-c, and T3) were identified in which the observed rate of pelvic LNI was distinctly different. Gleason primary grades were also combined (1-2, 3, and 4-5) because of a similar observation. Univariate analysis identified clinical tumor stage (p < 0.0001), Gleason primary grade (p < 0.0001), and serum prostate-specific antigen (p < 0.0001) as factors associated with pelvic LNI. Each of these variables retained independent significance (p < or = 0.0002) in the multivariate model. Patient age (p = 0.12) and history of prior transurethral resection of the prostate (p = 0.36) were not found to correlate with this endpoint. Probability plots provided an estimate of the likelihood for pelvic LNI according to the combination of pretherapy clinical tumor stage, Gleason primary grade, and serum prostate-specific antigen level. CONCLUSION: Clinical tumor stage as determined by digital rectal examination, Gleason primary grade of the diagnostic biopsy specimen, and pretherapy serum prostate-specific antigen value can be combined to estimate the probability of pelvic LNI for the patient with a new diagnosis of localized CaP. This information may be of value in directing the pretherapy diagnostic evaluation, as an aid in radiation therapy treatment planning, and in the conduct of clinical research efforts.

Adult↗
PubMed1996

Microvascular invasion of the seminal vesicles in adenocarcinoma of the prostate.

The objective of this article is to determine the relationship between microvascular invasion and seminal vesicle invasion in prostatic adenocarcinoma. Radical prostatectomies with seminal vesicle involvement were examined histologically and immunohistochemically with antibodies directed against S-100 protein and factor VIII. Microvascular invasion of the seminal vesicles showed a positive correlation with microvascular and capsular invasion of the prostate (P = 0.006 and 0.048, respectively) and lymph node metastases. Tumor progression was found in 8 of 14 (57%) patients with microvascular invasion of the seminal vesicles, compared with 3 of 22 (14%) without microvascular invasion (P = 0.001). Microvascular invasion of the seminal vesicles is predictive of tumor progression and lymph node metastases in prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Molecular biology of prostatic intraepithelial neoplasia.

High-grade PIN is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence to date. The clinical importance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN has a high predictive value as a marker for adenocarcinoma. Its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. PIN is associated with progressive abnormalities of phenotype and genotype intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. There is progressive gain or loss of a wide variety of biomarkers, including morphometric markers, differentiation markers, stromal markers, growth factors and associated receptors, oncogenes, tumor suppressor genes, and chromosomes. Abnormalities in expression of most biomarkers are amplified in the progression from high-grade PIN to localized cancer, metastatic cancer, and hormone-refractory cancer. Oncogenesis of prostatic carcinoma probably occurs through the selection of several genetic changes, each modifying the expression or function of genes controlling cell growth and differentiation. Further studies are needed to evaluate the function and prognostic value of oncogene expression in the normal, preneoplastic, and neoplastic prostate.

Adenocarcinoma↗
PubMed1996

Platelet-derived growth factor A and B chains and the alpha and beta receptors in prostatic intraepithelial neoplasia.

BACKGROUND: The objective of this study was to evaluate the expression of platelet-derived growth factor (PDGF A, PDGF B) and their receptors (PDGF alpha, PDGF beta) in prostatic intraepithelial neoplasia (PIN) and adenocarcinoma. METHODS: Peroxidase-antiperoxidase immunoperoxidase labeling was used to detect the extent of antibody labeling in 29 different high grade PIN specimens. RESULTS: PDGF A and PDGF alpha were uniformly expressed in glandular epithelial and stromal cells, whereas PDGF B was not expressed by either tissue. However, PDGF beta was lightly expressed in a uniform manner by both the glandular epithelial and stromal cells. CONCLUSIONS: The data suggest that an autocrine loop may exist in which the epithelial cells of high-grade PIN express PDGF AA and PDGF alpha to modulate growth of precancerous lesions.

Carcinoma in Situ↗
PubMed1996

Immunolocalization of glycoprotein A-80 in prostatic carcinoma and prostatic intraepithelial neoplasia.

A-80 is a mucin-like glycoprotein associated with exocrine differentiation that shows little or no expression in normal exocrine cells and typical adenomas, but is upregulated in dysplasia and adenocarcinoma of certain organs. Its expression has not been systematically examined in prostatic adenocarcinoma and its putative precursor, prostatic intraepithelial neoplasia (PIN). The authors applied a mouse monoclonal antibody against A-80 in paraffin-embedded sections from 103 cases of prostatic carcinoma, 26 cases of nodular hyperplasia, 7 autopsy samples from normal young adult prostates, and 12 fetal prostates. All but one cancer reacted, although expression was heterogeneous; 75 of 103 stained extensively (> 3+ on a 0 to 5+ scale) and strongly. Staining extent and intensity were independent of tumor grade, and tended to be strong even when focal. Seventy-seven of 84 foci (92%) of high-grade PIN and 38 of 52 foci (73%) of low-grade PIN stained for A-80; reactions were most extensive and intense in high grade PIN. Only 5 of 26 cases (19%) of hyperplasia reacted, and this consisted of weak to moderate staining in sporadic cells; the remainder were negative. Normal adult prostatic epithelium did not express A-80 except for weak and inconsistent staining in foci of inflammation and infarction; atrophic glands were negative. Fetal prostate showed focally strong reactivity. These results indicate that A-80 is selectively expressed in most cases of intraepithelial neoplasia and prostate cancer, but is usually absent in benign and hyperplastic epithelium. The upregulation of glycoprotein A-80 in PIN and adenocarcinoma parallels observations in other organs, such as the breast and colon, suggesting that this is a significant oncodevelopmental molecule with potential clinical applications.

Adult↗
PubMed1996

Prostatic intraepithelial neoplasia does not appear to raise serum prostate-specific antigen concentration.

OBJECTIVES: Conflicting findings have been reported regarding the relationship between prostatic intraepithelial neoplasia (PIN) and serum prostate-specific antigen (PSA) concentration. This study evaluates whether high-grade PIN significantly raises serum PSA concentration. METHODS: We evaluated 194 totally embedded whole-mounted radical prostatectomy specimens removed for clinically localized prostate cancer. No patient received preoperative therapy. In each specimen, the volume of high-grade PIN and carcinoma was calculated using the grid-counting method. Serum PSA concentration was determined prior to surgery. Cancer volume, gland weight, Gleason score, extraprostatic extension, and PIN volume were then compared according to serum PSA concentration and PSA density. RESULTS: Of the 194 patients, 170 (88%) had high-grade PIN-associated cancer and 24 (12%) had PIN-free cancer within the specimen. PIN volume ranged from 0 to 8.1 cc (mean, 1.3) and cancer volume ranged from 0 to 56.9 cc (mean, 9.1). In a subset of 93 patients with small cancers (less than 6.0 cc), PIN volume ranged from 0 to 6.1 (mean, 0.83) and did not correlate with serum PSA concentration or PSA density (P = 0.80 and P = 0.69, respectively). In the entire study group, PIN volume did not correlate with PSA density (P = 0.17), but did correlate with serum PSA concentration (P = 0.005). Using multiple regression analysis, adjusting for cancer volume, gland weight, Gleason score, and extraprostatic extension, log PIN volume did not contribute to log serum PSA concentration (regression coefficient -0.108; P = 0.51) or log PSA density (regression coefficient -0.104; P = 0.56) in small cancers (less than 6.0 cc). In the entire study group, log PIN volume did not contribute to log serum PSA concentration (regression coefficient -0.182; P = 0.05) or log PSA density (regression coefficient -0.202; P = 0.56). CONCLUSIONS: Our data indicate that high-grade PIN does not significantly contribute to serum PSA concentration. We suggest that patients with elevated serum PSA concentration found to have high-grade PIN on transrectal biopsy should not have their elevated serum PSA concentration attributed to high-grade PIN.

Aged↗
PubMed1996

Transurethral enzymatic ablation of the prostate: canine model.

OBJECTIVES: The purpose of this study was to investigate the toxicity and potential usefulness of transurethral prostatic injection of a collagenase-based solution in treating benign prostatic hyperplasia in dogs. METHODS: The injected solution contained collagenase, hyaluronidase, Triton X-100, and gentamicin. Twenty-one dogs were randomly divided into three groups for transurethral prostatic needle injection: two treatment groups were observed for 6 and 12 weeks and a control group was observed for 12 weeks. Laboratory studies, clinical monitoring, and complete postmortem examination were performed in all animals. RESULTS: Gross hematuria was noted in all dogs for a mean of 4 days after injection. No significant postoperative morbidity was noted. There were no significant differences in the values of laboratory tests among the three groups except for a mean increase in serum level of aspartate transaminase for treatment groups on postoperative day 1; this resolved by postoperative day 7. Histologically, all treated prostates had stromal atrophy and cystic acinar dilation involving about 30% of the gland without extraprostatic extension of these changes. The urethra, bladder, rectum, testicles, kidney, liver, and lungs were normal and intact in all animals. CONCLUSIONS: Transurethral injection of this enzyme solution creates a predictable, favorable histologic response in the canine prostate. The procedure appears safe and warrants further investigation for treatment of human benign prostatic hyperplasia.

Animals↗
PubMed1996

Optimized microvessel density analysis improves prediction of cancer stage from prostate needle biopsies.

OBJECTIVES: Clinical staging of prostate cancer is inaccurate, often with significant upstaging on final pathologic review. We previously demonstrated the ability to predict extraprostatic extension of cancer by use of the Gleason score and serum prostate-specific antigen (PSA) measurements. Herein we present an interim analysis of data from an ongoing multi-institutional study to determine the predictive power of an enhancement of microvessel density analysis in combination with Gleason score and serum PSA to predict extraprostatic extension. METHODS: We evaluated a total of 186 randomly selected biopsy samples and matched totally embedded radical prostatectomy samples with preoperative PSA concentrations and patient demographics. Gleason score and optimized microvessel density (OMVD) were determined from the needle biopsy samples; pathologic stage was verified by independent review of the radical prostatectomy samples. An automated digital image analysis system measured microvessel morphology and calculated the OMVD in the biopsy samples (Biostage; Bard Diagnostic Sciences, Seattle, Wash). RESULTS: Prediction of extraprostatic extension was increased significantly when OMVD analysis was added to Gleason score and serum PSA concentration (P = 0.003). CONCLUSIONS: Optimized microvessel density analysis significantly increases the ability to predict extraprostatic extension of cancer preoperatively when combined with Gleason score and serum PSA concentration. This method appears to be a useful tool that can assist with treatment decisions in selected patients.

Aged↗
PubMed1996

Potassium-titanyl-phosphate laser vaporization of the prostate: a comparative functional and pathologic study in canines.

OBJECTIVE: We compared the functional and pathologic results of potassium-titanyl-phosphate (KTP) laser vaporization prostatectomy with those of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser vaporization and coagulation prostatectomy in dogs. METHODS: The prostates of 41 dogs were treated with KTP laser vaporization (n = 21), Nd:YAG laser vaporization (n = 10), or Nd:YAG laser coagulation (n = 10). Dogs were sacrificed 2 days or 8 weeks after treatment. Prostates were weighed, measured, serially sectioned, and whole-mounted for histologic analysis. RESULTS: All techniques were hemostatic, and no irrigant absorption was detected. KTP laser vaporization produced a prostatic defect with a mean diameter of 3.0 and 2.4 cm at 2 days and 8 weeks postoperatively, respectively. Smaller defects (P < 0.0005 at 2 days and P < 0.02 at 8 weeks) were produced by Nd:YAG laser vaporization (2.0 and 1.4 cm, respectively) and coagulation (0.5 and 0.9 cm, respectively). No dog treated with KTP laser vaporization was incontinent or developed urinary retention, including 5 dogs whose urethral catheters were removed within 24 hours of surgery. CONCLUSIONS: KTP laser vaporization prostatectomy not only provides hemostasis similar to that obtained with Nd:YAG laser coagulation, but also removes tissue at the time of operation, allowing dogs to void without straining within 24 hours of treatment. In addition, the procedure is technically simple, and the operator has excellent control over exactly which tissue is removed and which is left intact. These findings suggest that KTP laser vaporization may be useful in the treatment of human benign prostatic hyperplasia.

Animals↗
PubMed1996

Temperature-correlated histopathologic changes following microwave thermoablation of obstructive tissue in patients with benign prostatic hyperplasia.

OBJECTIVES: To determine the intraprostatic pathologic changes following accurately measured doses of transurethral microwave thermal energy in patients with benign prostatic hyperplasia. METHODS: Eight patients scheduled for prostate surgery were treated for approximately 1 hour without anesthesia using a newly designed microwave treatment catheter that allows a close impedance match to prostate tissue and concentrates thermal energy preferentially in the anterior and lateral prostate gland. Interstitial, urethral, and rectal temperatures were continuously measured using a novel stereotactic thermal mapping technique. Serial sections of prostate tissue harvested during subsequent surgery were evaluated pathologically with prostate mapping. RESULTS: Microwave treatment resulted in marked and continuous intraprostate temperature elevation, while urethral and rectal temperatures remained low. Peak intraprostate temperatures in individual patients reached as high as 80 degrees C. Mean temperature reached a maximum of 54 degrees C at a radial distance of approximately 0.5 cm from the urethra and remained 45 degrees C or higher up to a distance of 1.6 cm. The predominant pathologic findings were uniform hemorrhagic necrosis and tissue devitalization without significant inflammation. The mean distance from the urethra to the viable-necrotic tissue border was 1.6 +/- 0.2 cm (range, 0.5 to 2.5). At this border, no more than 1 mm in thickness, temperature averaged 45.7 +/- 0.6 degrees C, and there was a suggestion that pure stromal nodules were more resistant to thermal injury. CONCLUSIONS: Microwave treatment can destroy obstructive prostate tissue while maintaining innocuous urethral and rectal temperatures. Temperatures of 45 degrees C or higher for approximately 1 hour cause uniform thermoablation of prostate tissue.

Body Temperature↗
PubMed1996

Absence of p16/MTS1 gene mutations in human prostate cancer.

The tumor suppressor gene p16/MTS1, located on chromosome 9p21, is a cell cycle regulatory gene which is frequently altered in human cancers. The role of this gene in prostate cancer is unknown. To determine the frequency of deletions and point mutations of p16/MTS1 in human prostate cancer, we examined 18 cancer and matched benign and hyperplastic tissue specimens. Deletions of p16/MTS1 were detected by semi-quantitative multiplex polymerase chain reaction in which a portion of exon 2 of the p16/MTS1 gene and a control marker, the glyceraldehyde 3-phosphate dehydrogenase gene, were amplified simultaneously. 'Cold' single-stranded conformational polymorphism (SSCP) analysis was performed to examine exons 1 and 2 of the p16/MTS1 gene for point mutations. Our data indicate no evidence for intragenic homozygous deletion in the prostate tumors. One prostate tumor and matched benign tissue showed mobility shifts. Direct DNA sequencing of the SSCP positive samples showed a G --> A transition in codon 140 which would result in an amino acid change from alanine to threonine. Our results indicate that deletions and point mutations in the p16/MTS1 gene are rare and do not play a major role in human prostate carcinogenesis.

Aged↗