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Toremifene for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: results of a double-blind, placebo controlled, phase IIB clinical trial.

PURPOSE: A randomized, double-blind, dose finding, placebo controlled, parallel group clinical study was done to determine the incidence of prostate cancer in men with high grade prostatic intraepithelial neoplasia treated with toremifene. MATERIALS AND METHODS: A total of 514 patients with high grade prostatic intraepithelial neoplasia and no evidence of prostate cancer on screening biopsy were randomized to 20, 40 or 60 mg toremifene, or placebo daily for 12 months. Patients underwent re-biopsy at 6 and 12 months. RESULTS: The number of evaluable patients, that is those with 1 on study biopsy who were compliant, was 447. The cumulative risk of prostate cancer was decreased in patients on 20 mg toremifene compared with placebo (24.4% vs 31.2%, p <0.05). The annualized rate of prevention was 6.8 cancers per 100 men treated. In patients with no biopsy evidence of cancer at baseline and 6 months, the 12-month incidence of prostate cancer was decreased by 48.2% with 20 mg toremifene compared with placebo (9.1% vs 17.4%, p <0.05). The 20 mg dose was most effective but cumulative and 12-month incidences of prostate cancer were lower for each toremifene dose vs placebo with a cumulative risk of 29.2% and 28.1%, and a 12-month incidence of 14.3% and 13.0% for 40 and 60 mg, respectively. Gleason scores were similar across treatments. The overall incidence of drug related and serious adverse events did not differ between any of the toremifene groups and the placebo group. CONCLUSIONS: Toremifene decreased the incidence of prostate cancer by 1 year and had a tolerability profile comparable to that of placebo in a high risk population.

Adult↗

Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases.

BACKGROUND: Prostate specific membrane antigen (PSM) is a membrane-bound antigen that is highly specific for benign and malignant prostate epithelial cells. Its expression in high grade prostatic intraepithelial neoplasia (PIN) has not been compared with that in prostate carcinoma. METHODS: The authors performed an immunohistochemical study of representative sections from 184 radical prostatectomies from previously untreated patients with pathologic stage T2N0M0 adenocarcinoma treated at the Mayo Clinic between 1987 and 1991. Affinity-purified monoclonal antibody 7E11-5.3 directed against PSM was employed at a concentration of 20 microg/mL overnight. For comparison, serial sections in each case were stained with prostate specific antigen (PSA). Staining for all antibodies was performed using the streptavidin-biotin method. For each case, the percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma was estimated in increments of 10%. Cox proportional hazards models were used to identify the risk of carcinoma recurrence according to the number of immunoreactive PIN or cancer cells for PSM and PSA; the date of radical prostatectomy was used as the starting time, and serum PSA (biochemical) failure or clinical failure was the event. PSA biochemical failure was defined as serum PSA > 0.2 ng/mL at least 30 days after surgery. RESULTS: Intense cytoplasmic immunoreactivity for PSM was observed in the benign and neoplastic epithelial cells in all cases (100% of cases staining). The number of cells staining was lower in benign epithelium and PIN than in adenocarcinoma (69.5+/-17.3% [range, 20-90%] vs. 77.9+/-13.2% [range, 30-100%] vs. 80.2+/-13.7% [range, 30-100%], respectively). With rare exceptions, basal cells were negative, and there was no immunoreactivity of the prostate stroma, urothelium, or vasculature. Adenocarcinoma gave the most intense and extensive staining, and the highest grades of adenocarcinoma (Gleason primary patterns 4 and 5) showed staining in virtually every cell; there was greater heterogeneity of staining in lower grades of adenocarcinoma. By contrast, PSA immunoreactivity was more intense and extensive in benign epithelium than in PIN and adenocarcinoma. The number of immunoreactive PIN or cancer cells for PSM and PSA was not predictive of PSA biochemical or clinical failure as defined in this study. CONCLUSIONS: PSM was expressed in all cases of prostate adenocarcinoma, with the greatest extent and intensity observed in the highest grades. The expression increased incrementally from benign epithelium to high grade PIN or adenocarcinoma. Conversely, PSA showed the greatest staining in benign epithelium, with decreased expression incrementally from benign epithelium to high grade PIN or adenocarcinoma. Expression of PSM is clinically useful for the identification of prostate epithelium, particularly PIN or adenocarcinoma, and its expression is regulated independent of PSA. The number of PSM immunoreactive cells was not predictive of recurrence, most likely because of the presence of abundant immunoreactivity in most cases, or because of differential expression in primary and metastatic disease.

Adenocarcinoma↗

Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia.

BACKGROUND: Evidence is accumulating that several proteases are involved in prostate cancer progression. A locus which is often amplified in prostate cancer is the chromosomal region 20q13. Interestingly, one of the genes encoding the cysteine protease cathepsin X maps to this region. The aim of this study was to assess the expression pattern of cathepsin X in malignant and non-malignant prostatic tissue samples. METHODS: Matched malignant and non-malignant tissue specimens were obtained from 56 men after radical prostatectomy. Cathepsin X was quantified at both protein and mRNA levels using several detection methods: Western blotting, immunohistochemistry, quantitative RT-PCR, and in situ hybridization. Furthermore, genomic DNA was analyzed by PCR for possible gene amplification. RESULTS: Immunohistochemical analysis of formalin-fixed, paraffin-embedded sections of radical prostatectomy specimens was performed utilizing a polyclonal antibody against human procathepsin X and revealed staining of acinar basal cells in normal prostate glands. Prostatic intraepithelial neoplasias (PINs) and prostate carcinomas stained highly positive for cathepsin X, showing a significant difference to the staining of normal prostate glands. In contrast, relatively weak and heterogeneous staining was observed for cathepsins F, B, and L. Up-regulation of cathepsin X at the protein level was confirmed by Western blotting. No statistically significant difference was observed at the mRNA level. PCR of genomic DNA revealed that cathepsin X up-regulation most likely occurs in the absence of genomic amplification. CONCLUSIONS: The high expression levels of cathepsin X both in PIN and invasive adenocarcinomas of the prostate suggest that cathepsin X may play a role in the early tumorigenesis of prostate cancer. Further studies are needed to define the utility of this cysteine protease as a diagnostic marker for the early detection of prostate cancer.

Aged↗

Prognostic significance of high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation in the contemporary era.

PURPOSE: High grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) in the sextant biopsy had been associated with a high risk of prostate cancer. We determined whether the extended biopsy schemes used in the contemporary era have altered the prognostic value of these lesions at repeat biopsies. MATERIALS AND METHODS: From 1998 to 2003, 105 of 1,188 men had at least 1 repeat extended biopsy due to the presence of HGPIN (33 men) or ASAP (72 men) in a previous extended biopsy. Median biopsy interval for HGPIN and ASAP was 15 and 10 weeks (p <0.05), respectively. Differences in cancer detection rates were analyzed using the Pearson chi-square test. RESULTS: In the HGPIN group only 1 of 22 (4.5%) men had cancer on 1st repeat biopsy and 0 of 11 men had cancer on 2nd repeat biopsy. In men with ASAP 19 of 53 (36%, p <0.005) had cancer on 1st repeat biopsy, and 3 of 19 (16%) had cancer on 2nd repeat biopsy. Cancer was confined to a single core in 16 of 22 (73%) men. Median Gleason score was 6. Patient age, digital rectal examination status, prostate specific antigen, free prostate specific antigen, number of cores and biopsy interval were not independent predictors of cancer in men with ASAP. CONCLUSIONS: HGPIN found in the contemporary extended biopsy does not warrant repeat biopsy. ASAP continues to be associated with a high risk of cancer and requires at least 1 repeat biopsy using the extended biopsy scheme.

Adult↗

Age and racial distribution of prostatic intraepithelial neoplasia.

AIMS: To study the prevalence, extent and evolution of high-grade prostatic intraepithelial neoplasia (HGPIN) in African-American and Caucasian men of a wide age range in order to help clarify the role this lesion may play in the racial differences of prostate cancer. METHODS: The lesion was documented in step-sectioned, entirely submitted prostates of two study populations: 525 autopsied men who died of trauma and 1,000 patients who had retropubic radical prostatectomy for clinically localized carcinoma of the prostate. RESULTS: We found that HGPIN starts in young individuals and increases progressively with advancing age in both races but is more prevalent in African-Americans. Additionally, the more extensive form of HGPIN with multifocal or diffuse involvement of the gland appears at a younger age in African-Americans. CONCLUSIONS: Microscopic foci of HGPIN can be documented in males in the 3rd and 4th decades with the lesion becoming more extensive in older men. The finding that HGPIN is both more prevalent and its more diffuse form appears earlier in African-Americans, indicates a potentially important role for this lesion in the race-related discrepancies associated with this disease.

Adult↗

[Incidence of high grade prostatic intraepithelial neoplasia in urologic practice].

High grade (PIN AG) intraepithelial neoplasia of the prostate is a likely precursor of prostate adenocarcinoma (PA) because of their association. Since the risk to suffer PA increases in patients with no previous PIN AG, its finding requires an arduous search for PA. This paper reviews the incidence of PIN AG in 499 histological studies in prostate transrectal biopsies, prostate TUR and adenomectomy specimens and radical prostatectomy (RP) sections. Evaluation of data obtained, type of presentation and association to prostate carcinoma, indicating the approach taken in the various cases.

Aged↗

Prostatic intraepithelial neoplasia and other changes during promotion and progression.

Preneoplastic lesions, early neoplastic lesions and carcinomas in situ have been demonstrated to be of great value for many purposes in many organ systems. Their recognition can be useful in epidemiological studies and can facilitate the selection of patients for therapeutic interventions. They can be used as "surrogate endpoint biomarkers" in studies aimed at the chemoprevention of cancers. In the lung, colon and various other organs, such markers are well recognized to be associated with the development of cancer in man. In the livers and colons of experimental animals, there has been detailed characterization of "enzyme-altered foci" (EAF) as "putative preneoplastic markers." The words "surrogate" and "putative" are important; the biological potential of these lesions needs to be elucidated in much greater detail. The quantification of early lesions that are associated with and sometimes precursors of neoplasia is of particular value because they are much more numerous, in most organ systems, than the carcinomas that develop in the same organs. The most abundant of these lesions show minimal or no morphological alterations. For example, EAF and aberrant crypts are more numerous than polyps in the colons of patients and experimental animals with cancer or precancerous conditions that affect the colon. Currently, there are few well documented putative or surrogate markers that are highly associated with the development of prostatic carcinoma in man. The best documented among these is prostatic intraepithelial neoplasia. We have recently reported the identification of EAF in the human prostate. While they share many phenotypic alterations with prostatic intraepithelial neoplasia, much remains to be accomplished if their biological fate is to be understood.

Animals↗

Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma.

OBJECTIVE: To evaluate individual nuclei from high grade prostatic intraepithelial neoplasia (PIN) lesions with early invasive carcinoma foci in the area of microinvasion and in the gland in which the microinvasion originated. STUDY DESIGN: High-resolution, digitized images of nuclei from defined locations were recorded and segmented, and karyometric variables were computed. These included a set of 93 features, which form a nuclear signature characterizing the spatial and statistical distribution of the nuclear chromatin. Nuclei in the glandular epithelium were recorded sequentially, along the basal cell layer, at increasing distances from the point of microinvasion and by random selection in the region of microinvasion. RESULTS: At a distance > 60 nuclear locations from the point of microinvasion, the nuclear signatures corresponded to those seen in high grade PIN. Between 40 and 20 nuclear locations removed from the microinvasion focus the signatures began to change gradually until at a distance of 15-5 locations they strongly resembled the signatures seen in adenocarcinoma. The total optical density decreased to values seen in adenocarcinoma, and the nuclear chromatin had finer granularity. While nuclei in high grade PIN followed a widely dispersed total optical density distribution suggestive of wide-ranging aneuploidy, the nuclei in the region of microinvasion exhibited a less dispersed and bimodal total optical density distribution. CONCLUSION: The chromatin texture signatures showed a clear trend: there was an obvious attenuation as the measured nuclei approached the microinvasion area. The decrease in total optical density at the microinvasion might suggest the emergence of one or two clones that can be responsible for the invasive phenotype.

Adenocarcinoma↗

Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia.

OBJECTIVE: Because of its long latency, slow growing nature, and high prevalence, prostate cancer is the best model for chemoprevention. High-grade prostate intraepithelial neoplasia (HGPIN) is a precursor of prostate cancer. Chemoprevention with lycopene has shown definite results in prostate cancer. We undertook a study to use lycopene as a chemopreventive agent in the treatment of HGPIN for preventing prostate cancer from developing in this vulnerable group of patients. MATERIALS AND METHODS: A total of 40 patients with HGPIN were randomized into 2 groups: one received 4 mg lycopene twice a day for one year, and the other was periodically followed up. Total follow-up was one year. RESULTS: Our results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer, and there exists an inverse relationship between lycopene and prostate-specific antigen. Being a vegetable carotenoid, lycopene is a safe drug to be used for a longer period without any adverse reaction. CONCLUSION: Lycopene is an effective chemopreventive agent in the treatment of HGPIN, with no toxicity and good patient tolerance.

Anticarcinogenic Agents↗

Interobserver reproducibility in the diagnosis of prostatic intraepithelial neoplasia.

To assess interobserver reproducibility in the categorization of prostatic intraepithelial neoplasia (PIN) seven pathologists reviewed 25 lesions. Rather than classic or consecutive examples of PIN, cases were selected to represent the full spectrum of diagnostic issues in this field. Lesions were classified into one of six categories: (a) benign prostate tissue, (b) PIN1, (c) PIN2, (d) PIN3, (e) PIN3 cannot rule out associated cancer, and (f) PIN3 plus cancer. Following evaluation of the slides, data were also analyzed by combining several of the groups into three categories: (a) benign/PIN1; (b) PIN2/PIN3/PIN cannot rule out cancer; and (c) PIN plus cancer. The level of agreement was fair (Kappa = 0.33) for the six categories and substantial (Kappa = 0.61) for the three groups. In no case was there a uniform diagnosis of PIN1; in all cases at least some pathologists considered the biopsies to be normal. This finding provides support for not commenting on PIN1 in biopsy material. In general, there was good distinction between low-grade PIN (PIN1) and high-grade PIN (PIN2-3). Among the seven cases for which there was a consensus that the lesion represented high-grade PIN, there was no case in which there was uniform agreement as to whether the lesion represented PIN2 or PIN3. This finding supports combining PIN2 and PIN3 into high-grade PIN. Cases classified as low-grade PIN by some and as high-grade PIN by others were those with pleomorphism but without prominent nucleoli. Difficulties in distinguishing "high-grade PIN" from "high grade PIN cannot rule out cancer" were those with cribriform glands, glands with necrosis, and where high-grade PIN was associated with only a few adjacent small atypical glands. These same histologies caused the participating pathologists difficulty in distinguishing "high-grade PIN cannot rule cancer" from "high grade PIN plus cancer."

Biopsy, Needle↗

Significance of high-grade prostatic intraepithelial neoplasia in needle biopsy specimens.

OBJECTIVES: To examine the significance of high-grade prostatic intraepithelial neoplasia (HGPIN) in biopsy specimens. METHODS: We performed sextant biopsies on a series of 83 cystoprostatectomy specimens removed for bladder cancer. For each case the number of foci and volume of both HGPIN and prostate cancer were assessed in the prostatectomy specimens and compared with the number of biopsy specimens involved by HGPIN. RESULTS: We identified HGPIN in 82 (99%) of 83 prostatic glands, whereas prostate cancer was found in 41 cases (49%). Corresponding sextant biopsies harbored both HGPIN and prostate cancer in 6 cases (7%), whereas only HGPIN was diagnosed in 29 sextant biopsies (35%). There was a positive correlation between the number of biopsy specimens containing HGPIN and the volume and multifocality of HGPIN in the corresponding prostatic glands. Prostates with HGPIN on sextant biopsy contained prostate cancer significantly more often when compared to cases with no HGPIN on sextant biopsy. Frequency of concurrent prostate cancer was higher in cases with two or more biopsy specimens containing HGPIN than in cases with only one such biopsy specimen, but case numbers of these categories were too small to render this difference statistically significant. CONCLUSIONS: The presence of HGPIN in sextant biopsies is a significant predictor of concurrent prostate cancer. Multifocality of HGPIN is a useful parameter in assessing the extent of HGPIN in the corresponding prostates. Its value in predicting a significantly increased risk of concurrent prostate cancer needs to be further investigated in larger case studies.

Adult↗

Evolution of isolated high-grade prostate intraepithelial neoplasia in a Mediterranean patient population.

The discovery of high-grade prostatic intraepithelial neoplasia (HGPIN) in prostatic needle biopsies is of clinical importance. Previous studies have shown prostate cancer to develop in 27-100% (average 55%) of the cases after HGPIN was diagnosed. Our preliminary findings in a Mediterranean population (Barcelona, Spain) revealed a prevalence of HGPIN of 4.4%, and an incidence of prostate cancer of 28.7% in cases in whom isolated HGPIN was identified at the first biopsy. The majority (64%) of these cases were diagnosed at the first biopsy after HGPIN diagnosis, and 52% within the first year. HGPIN persisted in 46.6% of the cases. The total mean serum prostate-specific antigen (PSA) was 9.9 +/- 6.6 ng/ml in the prostate cancer cases, compared with 8.8 +/- 7.5 in the cases without cancer. The low incidence of isolated HGPIN and subsequent cancer occurrence may be due to local factors or insufficient follow-up.

Biomarkers, Tumor↗

Progressive increase of apoptosis in prostatic intraepithelial neoplasia and carcinoma: comparison between in situ end-labeling of fragmented DNA and detection by routine hematoxylin-eosin staining.

OBJECTIVE: Apoptosis has attracted significant attention in the study of tumors during recent years. The first goal of this study was to evaluate the number of apoptotic cells and bodies in benign glands, in high-grade prostatic intraepithelial neoplasia, and in malignant prostatic glands. The second objective was to compare the effectiveness of in situ end-labeling of fragmented DNA (ISEL) with the use of routine hematoxylin-eosin (H&E) stains in the assessment of apoptosis rates. METHODS: The percentage of apoptosis was measured with ISEL and H&E stains in sections from 16 prostatectomies performed for previously untreated peripheral prostatic adenocarcinomas. RESULTS: Both methods showed progressive increase of the rates of apoptosis from benign glands (0.34% to 0.38%), to high-grade prostatic intraepithelial neoplasia (1.44% to 1.39%), to carcinoma (2.69% to 2.75%). The increase in apoptosis rate in prostatic intraepithelial neoplasia and carcinomas is one more indication of the continuum in the pathogenetic process leading to invasive prostatic carcinoma. Student's t test revealed no statistically significant difference in the percentage of apoptosis rendered by ISEL and H&E staining. CONCLUSIONS: From a practical point of view, evaluation of apoptosis with H&E stains can be readily performed using routine clinical material. The procedure is inexpensive, and it gives good tissue morphology. However, quantitative measurements may be time-consuming and observer-dependent. The apoptotic bodies are clearly identifiable with ISEL, making quantitation easy and even amenable to automated counting methods. Disadvantages of ISEL are significantly higher costs and poor tissue morphology. We conclude that accurate evaluation of apoptosis may be performed reliably with both routine H&E staining and the ISEL method. The decision to choose one method over the other depends on the economic resources available and the amount of material to be evaluated.

Adenocarcinoma↗

Histological markers of risk and the role of high-grade prostatic intraepithelial neoplasia.

The marked discrepancy between the prevalence of preclinical prostate cancer and the incidence of clinically manifest disease indicates a long latency phase and significant heterogeneity in the progression potential of early neoplastic lesions. There are a variety of histologic changes within prostatic epithelium that have been termed atypical or dysplastic. The 2 most widely studied of these lesions are prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). Although associations between AAH and adenocarcinoma are spurious, those linking high-grade PIN (HGPIN) to cancer are far more established. There is a significantly increased risk for patients with isolated HGPIN to have prostate cancer confirmed on subsequent biopsy, suggesting that HGPIN is a marker for prostate carcinoma in addition to its potential role as a premalignant lesion. Autopsy studies reveal that HGPIN is found in association with cancer in 63% to 94% of malignant and 25% to 43% of benign prostates. Data on age and race reveal that African American men develop more extensive HGPIN at a younger age than white men. A wide spectrum of molecular/genetic abnormalities appears to be common to both HGPIN and prostate cancer. Data loss of 8p, 10q, 16q, 18q, and gain of 7q31, 8q, multiple copies of the c-myc genes, along with changes in chromatin texture, telomerase activity, cell cycle status, and proliferative indices collectively suggest that HGPIN is intermediate between benign epithelium and prostatic carcinoma with respect to these markers. These data indicate that HGPIN is important in neoplastic progression, and may present an appropriate target/marker for chemoprevention.

Adenocarcinoma↗

Incidence and clinical significance of high-grade prostatic intraepithelial neoplasia in TURP specimens.

OBJECTIVES: To determine the incidence and clinical significance of high-grade prostatic intraepithelial neoplasia (PIN) in specimens obtained from transurethral resection of the prostate (TURP). METHODS: All TURP specimens accessioned to the general surgical pathology service of the Johns Hopkins Hospital (JHH) from March 1984 through December 1987 that did not contain adenocarcinoma of the prostate were reviewed for the presence of high-grade PIN (PIN 2 and PIN 3). These cases were supplemented with cases from the consultation files of the JHH, the Armed Forces Institute of Pathology, and the University of Michigan Hospitals. In total, 85 cases of high-grade PIN in TURP specimens were identified. RESULTS: The mean age of the patients at the time of TURP was 70 years and the median age was 71 years (range 50 to 89). Sixty-three patients (74%) were 65 years of age or older, 45 patients (53%) were at least 70 years of age, and 14 patients (16%) were 60 years of age or younger. Adenocarcinoma of the prostate was discovered in 9 (22%) of 41 patients with follow-up information. Based on material from JHH, the incidence of high-grade PIN was 2.3% in all TURP specimens and 3.2% in those without invasive carcinoma. CONCLUSIONS: High-grade PIN on TURP is relatively uncommon and is diagnosed in an elderly population. Patients with high-grade PIN on TURP appear to be at increased risk of developing prostatic carcinoma, although not to the same degree as patients with high-grade PIN on needle biopsy.

Aged↗

[Analysis of loss of heterozygosity on chromosome 6 in human prostate carcinoma and prostatic intraepithelial neoplasia].

OBJECTIVE: To detect the significance of loss of heterozygosity (LOH) on chromosome 6 in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN). METHODS: Pure DNA was obtained from prostate neoplasms and normal tissues after tissue microdissection. LOH of chromosome 6 was detected by PCR based microsatellite polymorphism analysis technique using 20 pairs of microsatellite primers in 10 prostate carcinoma cases and 10 high grade PIN cases. RESULTS: Allelic loss at one or more loci was observed on chromosome 6 in 8 of 10 prostate carcinoma cases. 6q21-6q23 and 6q25-6q27 were two of LOH high frequency regions. 5 high grade PIN cases had LOH detected on chromosome 6. CONCLUSIONS: Two high frequency LOH regions were detected on chromosome 6 of prostate carcinoma. Cyclin C, IGF2R genes were two candidate tumor suppressor genes located in these two regions, they may be involved in the initiation and progression of prostate cancer.

Aged↗

[Analysis of loss of heterozygosity on chromosome 8 in human prostate carcinoma and high grade prostatic intraepithelial neoplasia].

OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 8 in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN). METHODS: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. LOH on chromosome 8 was detected by PCR based microsatellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade PIN. RESULTS: There were different frequencies of LOH on chromosome 8 in 10 samples of prostate carcinoma. 8p23.1-p23.2 and 8p21-p22 were two high-frequency LOH regions. LOH on chromosome 8 was detected in 3 samples of high grade PIN. CONCLUSIONS: There were high-frequency LOH regions on chromosome 8 of prostate carcinoma, located on 8p23.1-p23.2 and 8p21-p22. High grade PIN and prostate carcinoma share the same allelic loss on 8p. Tumor suppressor genes located at these two regions may be potentially involved in the initiation and progression of prostate carcinoma.

Aged↗