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PubMed2003

Multilocular prostatic cystadenoma with high-grade prostatic intraepithelial neoplasia.

Multilocular prostatic cystadenoma is a rarely encountered neoplasm located in the midline between the bladder and rectum that is either attached to the prostate by a pedicle or separate from the prostate entirely. Histologically and immunohistochemically these lesions resemble benign prostate tissue. We report the first case of this entity for which multifocal high-grade prostatic intraepithelial neoplasia (PIN) is identified. Conceptually, the finding of high-grade PIN in multilocular prostatic cystadenomas provides further evidence that these lesions are fully analogous to the prostate gland not only in their morphology and immunohistochemistry but also in their predilection for the same diseases.

Cystadenoma↗

PubMed1999

Expression of the RNA component of human telomerase (hTR) in prostate cancer, prostatic intraepithelial neoplasia, and normal prostate tissue.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. While telomerase is undetectable in most normal somatic tissues, telomerase activation has been detected by a polymerase chain reaction (PCR)-based assay (TRAP) in many immortal cell lines and various cancers, including prostate cancers. To investigate the role of telomerase in prostate cancer at the cellular level, the expression of one of the ribonucleoprotein complexes, the RNA component of human telomerase (hTR), was studied in normal, preneoplastic, and cancerous prostate tissues using a non-radioactive in situ hybridization procedure. Nine human prostates resected at the time of radical prostatectomy were studied. In each case, archival paraffin-embedded samples from normal tissue, prostatic intraepithelial neoplasia (PIN) lesions, the putative precancerous lesion, and prostate carcinomas were selected for in situ hybridization. hTR mRNA expression was detected in carcinomatous glands of seven out of the nine cancers (75 per cent). Furthermore, in seven out of the eight cases showing PIN lesions, the epithelial cells of PIN foci also expressed hTR mRNA. By contrast, in normal tissue, epithelial cells were negative, whereas hTR mRNA expression was detected in the basal cells. The detection of hTR mRNA in PIN lesions clearly strengthens the link between PIN and carcinomatous glands and suggests that telomerase expression occurs early in prostate carcinogenesis. Furthermore, this study confirms previous experimental data suggesting that the basal cell layer is the stem cell compartment in prostate.

Aged↗

PubMed1998

Immunohistochemical expression of retinoblastoma and p53 tumor suppressor genes in prostatic intraepithelial neoplasia: comparison with prostatic adenocarcinoma and benign prostate.

Mutational alterations involving the p53 and retinoblastoma (RB) tumor suppressor genes are implicated in the oncogenesis of a variety of tumors. Their role in the pathogenesis of prostatic adenocarcinoma remains to be fully elucidated, and their detection in high-grade prostatic intraepithelial neoplasia (HG-PIN) has not been closely examined. We studied the immunohistochemical expression of RB and p53 proteins in HG-PIN, benign prostate, and prostatic adenocarcinoma from 25 radical prostatectomy specimens. Formalin-fixed, paraffin-embedded tissue sections pretreated with antigen retrieval in citrate buffer were stained with anti-RB antibody RB-WL-1 and anti-p53 antibody DO-7. RB immunoreactivity was present in all of the cases in the foci of HG-PIN, benign prostate, and prostatic adenocarcinoma. Mutant p53 protein was detected in 56% of HG-PIN, 72% of prostatic adenocarcinomas, and 20% of benign prostatic glands. A multivariate analysis of variance showed an overall difference in p53 immunoreactivity between HG-PIN, benign prostate, and prostatic adenocarcinoma (P < .001). There was a statistically significant difference between immunoreactivity of the benign prostate and of HG-PIN (P < .001) and between the immunoreactivity of benign prostate and prostatic adenocarcinoma (P < .001). The immunoreactivities of HG-PIN and prostatic adenocarcinoma were not statistically different (P = .3). These data suggest that RB loss might not play a role in initiation of all cases of prostatic adenocarcinoma. The p53 immunoreactivity in HG-PIN was significantly different from that found in benign prostate and was similar to that of prostatic adenocarcinoma. This is in keeping with the putative premalignant character of HG-PIN.

Adenocarcinoma↗

PubMed1998

Expression of Bcl-2, Bax, and p53 in high-grade prostatic intraepithelial neoplasia and localized prostate cancer: relationship with apoptosis and proliferation.

BACKGROUND: Apoptosis-regulating genes have been shown to be important in the biology of prostate cancer. The aim of this study was to examine and correlate the expression of the apoptosis-regulating genes bcl-2, bax, and p53 with the frequency of apoptosis and rate of proliferation in benign prostatic epithelium (BP), prostate cancer, and high-grade prostatic intraepithelial neoplasia (HGPIN), which is currently considered the most likely precursor of prostate cancer. METHODS: Forty-four patients with histologically proven prostate cancer were investigated. All the men underwent radical prostatectomy. Immunohistochemistry was performed to assess expression of bcl-2, bax, and p53, and proliferation rate, as measured by the Ki-67 index. The frequency of apoptotic bodies was assessed by morphological criteria. RESULTS: The apoptotic index (AI) was highest in prostate cancer, and was significantly greater in HGPIN compared to benign prostate. The Ki-67 index was greatest in cancer, intermediate in HGPIN, and lowest in BP. The AI was increased in areas of BP in patients treated with neoadjuvant androgen ablation. No change in AI was seen in treated cases of HGPIN or cancer. Accumulation of p53 protein was infrequent in prostate cancer (2/43: 4.6%), and was absent in HGPIN. Bcl-2 overexpression was present in 2.3% of cancers (1/43) and in 34.9% of cases of HGPIN (15/43). Bax expression was seen in all cases of cancer and HGPIN. There was no correlation between bcl-2 expression and the apoptotic and Ki-67 indices in HGPIN. CONCLUSIONS: p53 and bcl-2 expression is infrequent in clinically organ confined prostate cancer. Bcl-2 expression is significantly higher in HGPIN than in both the associated prostate cancer and BP. The AI and Ki-67 index appeared intermediate in the putative precursor lesion HGPIN compared to prostate cancer and BP.

Androgens↗

PubMed2004

Monofocal and plurifocal high-grade prostatic intraepithelial neoplasia on extended prostate biopsies: factors predicting cancer detection on extended repeat biopsy.

OBJECTIVES: To evaluate factors predicting cancer detection by extended repeat prostate biopsies in patients with an initial, isolated, monofocal or plurifocal, high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. METHODS: From 1995 to 2002, after a first set of 10 to 12 systematic biopsy cores, 47 patients with an initial HGPIN diagnosis underwent repeat biopsy using the same technique (mean repeat biopsy cores 11.5) after a median follow-up of 11.4 months (range 3 to 24). RESULTS: Cancer was detected at the second biopsy in 21 patients (44.6%). Cancer detection was significantly greater in patients with plurifocal HGPIN than in those with monofocal HGPIN (70% vs. 10%, respectively; P <0.005) and in patients who underwent repeat biopsy more than 6 months after the first biopsy set (65%) compared with patients who underwent repeat biopsy within 6 months (25%; P <0.01; mean follow-up 15.5 and 3.8 months, respectively). Multivariate analysis showed that prostate-specific antigen, prostate-specific antigen density, digital rectal examination, and transrectal ultrasound findings were not statistically significant predictors of prostate cancer, and HGPIN multifocality and interval between biopsies (more than a 6-month follow-up interval) were independent prognostic factors (odds ratio 4.65 and 2.65, respectively). After radical prostatectomy (14 patients), no statistically significant differences were found in the pathologic stage between patient groups stratified by repeat biopsy interval (within or after 6 months). CONCLUSIONS: After a 10 to 12-core biopsy, patients with initial, isolated monofocal or plurifocal HGPIN diagnoses had an overall cancer detection rate of 45% on repeat extended biopsies. Plurifocal HGPIN on the first biopsy set was the strongest independent predictive factor in cancer detection. A 12 to 18-month interval before repeat biopsy could permit a significantly greater cancer detection rate, with no apparent likelihood of clinical cancer progression.

Aged↗

PubMed2001

Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer.

SUMMARY: Fibroblast growth factor 8 (FGF-8) is implicated in growth of prostate cancer. Alternative splicing of the human FGF-8 gene potentially allows coding for four protein isoforms (a, b, e, and f). These isoforms differ in their binding to FGF receptors (FGFR) and in their mitogenic and transforming capacity in transfection assays. Here, we used RT-PCR and immunohistochemistry to study the expression of FGF-8 and FGFR isoforms in human prostate cancer (n = 31). Nonmalignant prostate specimens from cystoprostatectomies (n = 24) were examined as controls. Most prostate cancer samples and some control prostates also contained prostatic intraepithelial neoplasia (PIN) lesions. FGF-8a and e were expressed at significantly higher frequencies in prostate cancer (FGF-8a, 55%; FGF-8e, 45%) than in control samples (FGF-8a, 17%, p = 0.0052; FGF-8e, 8%, p = 0.0031). On the contrary, FGF-8b was found at an equal frequency in prostate cancer (55%) and in control prostates (50%). Furthermore, a combination of two or three FGF-8 isoforms (a, b, and/or e) was also expressed at a higher frequency in prostate cancer than in control samples (45% and 8%, respectively, p = 0.0031). Immunohistochemistry with an antibody recognizing all FGF-8 isoforms was more strongly immunoreactive in prostate cancer cells and PIN lesions than in normal-type epithelium. The receptor splicing variants FGFR1IIIc and FGFR2IIIc, which are activated by FGF-8, were found both in prostate cancer and control samples. Interestingly, immunoreactivity for FGFR1 and FGFR2 was much stronger in prostate cancer cells and PIN than in normal epithelium. These results demonstrate, for the first time, that FGF-8 isoforms and their receptors FGFR1IIIc and FGFR2IIIc are expressed at an increased level not only in prostate cancer but also in premalignant PIN lesions. These data suggest that FGF-8 may have an important autocrine role in the development of human prostate cancer. In addition to FGF-8b, the FGF-8 isoforms a and e may be involved in this process.

Aged↗

PubMed2004

Pim-1 expression in prostatic intraepithelial neoplasia and human prostate cancer.

BACKGROUND: PIM-1, an oncogene product of serine/threonine kinase, has been found to play an important role in induction/suppression of apoptosis, cell cycle progression, and transcriptional regulation by phosphorylating the target proteins involved in these processes. Recently, the expression of PIM-1 has been shown to correlate significantly with measures of prostate cancer clinical outcome. METHODS: Immunohistochemical analysis was used to characterize the patterns of PIM-1 expression in high grade prostatic intraepithelial neoplasia (HGPIN) and cancer in 121 radical prostatectomy specimens. RESULTS: Moderate to strong cytoplasmic staining was observed in 68% of cancers, 12% presented nuclear positivity as well. Moderate to strong expression was seen in 76% of tumors with Gleason score (GS) 7 or higher compared to 58% in tumors with GS 6 or lower (P = 0.04). The staining intensity was moderate or strong in 97% of HGPIN lesions. PIM-1 was overexpressed in HGPIN compared to cancer in 65% of cases. Expression in benign glands was negative or only weakly positive. CONCLUSION: Our data suggest that PIM-1 overexpression in HGPIN may be an early event in the development of prostate malignancy. Additionally, PIM-1 expression provides supplementary information for distinguishing HGPIN from benign epithelium.

Aged↗

PubMed2000

Expression of a kallikrein-like protein in prostatic intraepithelial neoplasia in ventral prostate of the noble rat.

BACKGROUND: In an effort to identify biomarker(s) for prostatic cancer (PCa), we analyzed the changes of secretory proteins in the ventral prostate (VP) of Noble rats at early stages of carcinogenesis. METHODS: Ventral prostates were removed from both control (n = 36) and experimental (n = 88) rats implanted with a known ratio of testosterone (T) and 17beta-estradiol (E(2)). Tissue sections were stained by hematoxylin and eosin (H&E) for pathological screening, and secretions were collected for SDS-PAGE analysis followed by N-terminal microsequencing, antiserum production, Western blot, and immunohistochemical study. RESULTS: Pathologically, low-grade prostatic intraepithelial neoplasia (LGPIN) and high-grade PIN (HGPIN) were observed in ducts or alveoli after 3 and 5 months of T + E(2) treatment, respectively. The results of SDS-PAGE showed an elevated expression of 18-kDa protein (p18) in secretions of VP with HGPIN or cancerous lesions. Analysis of p18 by N-terminal sequencing showed a high score of homology to rat glandular kallikrein. To characterize the expression pattern of the protein in tissue samples, an antiserum was raised against the N-terminus of the p18. The monospecificity of the antiserum against p18 was confirmed by Western blot analysis. Immunohistochemical study showed that in ducts or alveoli of normal and LGPIN samples, a mild positive staining for p18 was observed in secretions. However, the reactivity was intense not only in luminal secretions but also in some luminal secretory cells in HGPIN and cancer cells as well. CONCLUSIONS: The high expression of p18 in connection with neoplastic transformation of cells strongly suggests that the potential application of this protein as a marker for early detection of PCa should be further investigated.

Adenocarcinoma↗

PubMed1999

The effect of high grade prostatic intraepithelial neoplasia on serum total and percentage of free prostate specific antigen levels.

PURPOSE: It is established that the percentage of free prostate specific antigen (PSA) in serum is low in patients with prostate cancer. An unanswered question is whether a low percentage of free PSA can be explained by high grade prostatic intraepithelial neoplasia alone. We compared the percentage of free PSA in men with high grade prostatic intraepithelial neoplasia alone, prostate cancer, benign prostatic hyperplasia (BPH) and a normal prostate (that is normal digital rectal examination and PSA less than or equal to 2.5 ng./ml.). MATERIALS AND METHODS: From October 1994 through December 1997, 48 men were diagnosed with high grade prostatic intraepithelial neoplasia without concomitant prostate cancer. Of these men 43 with a mean age plus or minus standard deviation of 67.4 +/- 7.8 years comprised our study group. To date none has been diagnosed with cancer during followup. Serum free and total PSA levels were measured, and the percentage of free PSA was calculated. The percentage of free PSA in the 43 men was compared to that in 50 with prostate cancer (mean age 65.4 +/- 7.8 years), 50 with biopsy proved BPH (67 +/- 7) and 43 with a normal prostate (61 +/- 8). RESULTS: There was no significant difference in mean total serum PSA in patients with high grade prostatic intraepithelial neoplasia, prostate cancer or BPH. The percentage of free PSA was significantly lower in patients with prostate cancer (14.9 +/- 6.5%) than those with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%), BPH (20.1 +/- 7.3%) or a normal prostate (27.7 +/- 12.2%). There was also no significant difference in the percentage of free PSA between men with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%) and those with BPH (20.1 +/- 7.3%). Additionally, men with a normal prostate had a higher percentage of free PSA (27.7%) than those with BPH (20.1%), high grade prostatic intraepithelial neoplasia (20.8%) or prostate cancer (14.9%). CONCLUSIONS: The percentages of free PSA in men with high grade prostatic intraepithelial neoplasia and BPH are similar, and significantly higher than those found in men with prostate cancer.

Aged↗

PubMed2001

The critical role of patient follow-up after receiving a diagnosis of prostatic intraepithelial neoplasia.

With the increasing incidence of prostatic intraepithelial neoplasia being found at the time of prostate biopsy and the association of prostatic intraepithelial neoplasia to coexisting prostate cancer and/or the future development of prostate cancer, patient compliance in following post-biopsy follow-up instructions for re-biopsy is becoming more significant in the detection of prostate cancer at an earlier and, therefore, potentially curable stage. During a 3-y period, we reviewed the charts of 130 patients who received an initial diagnosis of prostatic intraepithelial neoplasia after undergoing transrectal ultrasound of the prostate with biopsy. It is our policy to inform the patient of their diagnosis of prostatic intraepithelial neoplasia at the time of the initial biopsy and to recommend a repeat biopsy in 6-12 months. Patients are informed of the diagnosis of prostatic intraepithelial neoplasia verbally and in writing. In addition, a letter is sent to their referring physician with the re-biopsy recommendation. Thirty-nine of 130 patients (30%) were seen for re-biopsy within the specified time. An additional 36 patients (27.69%) were re-biopsied between 12 and 18 months after the initial diagnosis of prostatic intraepithelial neoplasia. An additional 11 patients (7%) were re-biopsied more than 18 months after their initial diagnosis. Forty-four patients failed to return for re-biopsy. Overall, patient follow-up within the desired protocol was poor and must be improved upon to prevent any delays in the diagnosis of prostate cancer. Prostate Cancer and Prostatic Diseases (2001) 4, 63-66

Journal Article↗

PubMed2004

High-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic carcinoma. The only method of detection is biopsy; prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultra-sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%-16%), representing 115,000 new cases of PIN diagnosed each year in United States. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeated biopsy for concurrent or subsequent invasive carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

Journal Article↗

PubMed2003

Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model.

To determine whether Akt activation was sufficient for the transformation of normal prostate epithelial cells, murine prostate restricted Akt kinase activity was generated in transgenic mice (MPAKT mice). Akt expression led to p70S6K activation, prostatic intraepithelial neoplasia (PIN), and bladder obstruction. mRNA expression profiles from MPAKT ventral prostate revealed similarities to human cancer and an angiogenic signature that included three angiogenin family members, one of which was found elevated in the plasma of men with prostate cancer. Thus, the MPAKT model may be useful in studying the role of Akt in prostate epithelial cell transformation and in the discovery of molecular markers relevant to human disease.

Animals↗

PubMedDate not supplied

High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases.

The relationship of prostatic intraepithelial neoplasia (PIN) and invasive carcinoma of the prostate is not fully understood. It is generally accepted that HGPIN is a probable preinvasive malignant change or at least a marker lesion for carcinoma. The prevalence of HGPIN in younger men is not known. Two hundred and forty nine entirely processed prostates from men aged 20-69 were thoroughly evaluated for the presence of PIN and carcinoma. The histologic diagnosis of all positive cases was confirmed by two pathologists. Our results are summarized as follows: Seventy seven percent of the prostates with HGPIN harbored adenocarcinoma, whereas the frequency of cancer in prostates without HGPIN was 24%. HGPIN was encountered in 0, 5, 10, 41 and 63% of men in the 3rd, 4th, 5th and 7th decades, respectively. The corresponding figures for invasive carcinoma were 2, 29, 32, 55, and 64% respectively.

Adenocarcinoma↗

PubMed1997

The extent and multicentricity of high-grade prostatic intraepithelial neoplasia in clinically localized prostatic adenocarcinoma.

High-grade prostatic intraepithelial neoplasia (PIN) is considered the most likely precursor of invasive prostatic adenocarcinoma, and is characterized by cellular proliferations within preexisting ducts and glands with cytological changes mimicking cancer. The extent and multicentricity of this clinically important histopathologic lesion have not been fully defined. We sought to determine whether the extent and zonal distribution of PIN are related to prostate cancer. A total of 195 whole-mounted radical prostatectomy specimens were evaluated. All patients had clinically localized cancer, and none had received preoperative therapy. The zonal location and multicentricity of PIN were recorded, and the volume of PIN was measured using a grid-counting method according to pattern (tufting, micropapillary, cribriform, and flat) and spatial proximity to cancer (less than or equal to 2 mm from cancer, and greater than 2 mm from cancer). The results were correlated with patient age, prostate volume, cancer volume, pathological stage, and Gleason grade. High-grade PIN was identified in 86% of cases, usually with multiple architectural patterns of PIN in each positive case: tufting (97% of cases), micropapillary (66% of cases), cribriform (19% of cases), and flat (21% of cases). The mean volume of PIN was 1.32 cm3 (standard error [SE], 0.10; range, 0 to 8.12 cm3), and was greater for PIN within 2 mm of cancer (mean, 1.0 cm3) than for PIN more than 2 mm from cancer (mean, 0.3 cm3). PIN was usually multicentric (64.5% of cases) and located in the nontransition zone (63%) or all zones (36%) of the prostate. There was a positive correlation of total volume of PIN and volume of cancer, but this correlation was significant only for PIN within 2 mm of cancer. The volume of PIN was positively correlated with age, pathological stage, and Gleason score; most of these positive correlations were caused by PIN within 2 mm of cancer rather than that greater than 2 mm from cancer. Our results indicate that the extent and zonal distribution of high-grade PIN and carcinoma are strongly associated, and that PIN is frequently multicentric. This supports the hypothesis that PIN is a premalignant lesion.

Adenocarcinoma↗

PubMed2001

High-grade prostatic intraepithelial neoplasia with adjacent atypia is associated with a higher incidence of cancer on subsequent needle biopsy than high-grade prostatic intraepithelial neoplasia alone.

OBJECTIVES: High-grade prostatic intraepithelial neoplasia (HGPIN) is often considered a premalignant lesion of the prostate. Its incidence ranges from 0.7% to 20% in all prostate biopsies, and patients with HGPIN on initial biopsy are reportedly found to have a higher risk of cancer on subsequent biopsy. The purpose of our study was to determine the incidence of HGPIN in our patients who underwent prostate biopsy and to determine whether a further pathologic subclassification of HGPIN between HGPIN alone and HGPIN with adjacent atypical glands has any prognostic value in predicting the rate of prostate cancer on subsequent prostate biopsy. METHODS: A total of 485 patients who underwent prostate biopsy between January 1998 and October 1999 were included in the study. Each set of slides was reviewed by a single urologic pathologist to determine the presence of HGPIN alone or HGPIN with adjacent atypical glands. If any HGPIN was identified, a repeat biopsy was performed, and the presence of cancer was recorded. RESULTS: The overall incidence of HGPIN alone and HGPIN with adjacent atypical glands on initial biopsy was 33 (6.8%) of 485. Of these 33 patients, 21 (64%) had HGPIN alone and 12 (36%) had HGPIN with adjacent atypical glands. Three (14%) of 21 patients with HGPIN alone were found to have cancer on subsequent biopsy compared to 9 (75%) of 12 patients with HGPIN with adjacent atypia on initial biopsy. This difference is statistically significant (P <0.005). CONCLUSIONS: The incidence of HGPIN alone in our experience is 4.3% (21 of 485). Patients with HGPIN with adjacent atypical glands suspicious for cancer have a significantly higher incidence of cancer on subsequent biopsy than patients with HGPIN alone.

Aged↗

PubMed1991

Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma.

Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma.

Carcinoma↗

PubMed2002

Followup interval prostate biopsy 3 years after diagnosis of high grade prostatic intraepithelial neoplasia is associated with high likelihood of prostate cancer, independent of change in prostate specific antigen levels.

PURPOSE: Repeat biopsy has been advocated following the diagnosis of high grade prostatic intraepithelial neoplasia to exclude coexisting prostate cancer. We further define the natural history of high grade prostatic intraepithelial neoplasia by determining the incidence of prostate cancer 3 years following diagnosis. MATERIALS AND METHODS: A total of 31 men underwent followup interval biopsy 3 years after high grade prostatic intraepithelial neoplasia diagnosis in 1996 to 1997, regardless of change in serum prostate specific antigen (PSA) or digital rectal examination findings. A single pathologist reviewed all biopsy specimens. All men had a minimum of 12 biopsy cores taken at the time of diagnosis. RESULTS: A 3-year followup interval biopsy eight (25.8%) men had prostate cancer, 11 (35.5%) had high grade prostatic intraepithelial neoplasia only and 12 (38.7%) had no disease. Mean serum PSA at diagnosis and before the followup biopsy was 6.88 and 9.69 ng./dl., respectively (p = 0.008). Of the men 48% had less than a 1.0 unit increase in serum PSA. Upon univariate regression analysis change in serum PSA was not associated with the detection of prostate cancer (p >0.10). All 4 patients who subsequently underwent radical prostatectomy had organ confined disease. CONCLUSIONS: In a high proportion of men with high grade prostatic intraepithelial neoplasia prostate cancer will develop in a 3-year interval. Our findings support the concept that high grade prostatic intraepithelial neoplasia is a precursor to prostate cancer and that repeat biopsy at a delayed interval is recommended regardless of changes in PSA.

Adenocarcinoma↗

PubMed1997

Relationship between atypical adenomatous hyperplasia (AAH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma.

Two histopathologic lesions are considered putative precursors of prostate cancer, but the supportive evidence for one (prostatic intraepithelial neoplasia, or PIN) is much greater than the other (atypical adenomatous hyperplasia, or AAH). High grade PIN is the most likely precursor of carcinoma, arising in the peripheral zone, but probably does not account for well-differentiated cancer arising in the transition zone. The biological significance of atypical adenomatous hyperplasia of the prostate (AAH) is inconclusive at the time. The histological and cytological features of AAH are intermediate between BPH and low grade carcinoma, suggesting that AAH may be a precursor of well differentiated transition; zone carcinoma. In the recent time new findings on morphogenetic aspects of normal and abnormal prostatic growth i.e. stem cell models are discussed and topics about grading and proliferative activities, frequency and histological changes associated with aging as well as clinical relevance of PIN and AAH. This paper reviews the results and discussion at the second international consultation meeting on PIN in Mayo Clinic, Rochester, Nov. 3-4 th. 1995, following the first international consultation meeting of AAH and PIN and origin of the prostatic carcinoma in Ancona, Sept. 11-12 th 1994.

Adenocarcinoma↗