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PubMed2001

Is repeat prostate biopsy for high-grade prostatic intraepithelial neoplasia necessary after routine 12-core sampling?

OBJECTIVES: To determine whether repeat biopsy is necessary when the diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) is made with a 12-core biopsy. Repeated biopsy has been recommended for individuals with HGPIN noted on sextant prostate biopsy because of the high likelihood of cancer detection. Recently, we have recommended the routine use of 12 cores, rather than 6, to improve cancer detection. METHODS: The charts of all patients undergoing prostate biopsy during a 2-year period at the Manhattan Veterans Administration Medical Center were reviewed. Patients diagnosed with HGPIN on a 12-core biopsy were identified, and those undergoing a repeat 12-core biopsy within 1 year of the initial biopsy were evaluated to determine the rate of cancer detection. RESULTS: A total of 619 men underwent biopsy during the study period. Of 103 men diagnosed with HGPIN, 43 underwent a repeat biopsy within 1 year at the discretion of the managing urologist. The mean age and median prostate-specific antigen level of those undergoing a repeat biopsy was 65.5 years and 5.37 ng/mL, respectively. At the time of the repeat biopsy, 1 patient was found to have cancer (2.3%), 20 had HGPIN (46.5%), 20 had benign pathologic findings (46.5%), and 1 patient (2.3%) had atypical small acinar proliferation. CONCLUSIONS: A repeat biopsy after the diagnosis of HGPIN on 12-core prostate biopsy rarely results in cancer detection. In the absence of other factors increasing the suspicion of cancer, immediate repeat biopsy for HGPIN diagnosed on a 12-core biopsy is unnecessary.

Aged↗
PubMed2004

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin packaging and phenotype, with the nuclei from the flat high-grade PIN lesions, adjacent normal looking epithelium and co-occurring adenocarcinoma expressing a greater nuclear abnormality than in the specimens with cribriform high-grade PIN.

Cell Nucleus↗
PubMed1997

Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma.

The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma.

Carcinoma↗
PubMed2004

Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia.

To date, several reports have been published about CpG island methylation of various genes in prostate cancer. However, most of these studies have focused on cancer tissue only or a single gene and data about concurrent methylation of multiple genes in prostate cancer or prostatic intraepithelial neoplasia (PIN) are limited. The aim of the present study was to determine the methylation profile of 11 tumour-related genes in prostate cancer and PIN. Seventy-one samples, including 37 prostate cancers, 14 PINs, and 20 normal prostates, were examined for the methylation status of 11 tumour-related genes using methylation-specific PCR. The mean number of genes methylated was significantly higher in prostate cancer and PIN than in non-neoplastic prostate (4.4, 3, and 0.2, respectively; p < 0.001). In prostate cancer, APC, GSTP1, MGMT, and RASSF1A were frequently methylated at a frequency of 56.8%, 86.5%, 75.7%, and 83.8%, respectively. These genes were methylated in more than 30% of PINs. Prostate cancers with high serum prostate-specific antigen (PSA) (more than 8 ng/ml) or a high Gleason score (GS) (3 + 4 or more) showed higher numbers of methylated genes than those with low serum PSA (8 or less) or low GS (3 + 3 or less) (5.4 versus 2.5 and 5.4 versus 3.1, respectively; p < 0.05). The methylation frequency of APC, RASSF1A, and RUNX3 was higher in prostate cancers with high serum PSA or with high GS than in those with low PSA or with low GS, respectively, the differences reaching statistical significance (p < 0.05). A strong association between MGMT methylation and loss of MGMT expression was demonstrated by immunohistochemistry. CpG island methylation is a frequent event, occurs early, and accumulates during multi-step prostatic carcinogenesis. High levels of CpG island hypermethylation might serve as a potential biological marker for aggressive prostate cancer.

Adenocarcinoma↗
PubMed2003

Clinical management of prostatic intraepithelial neoplasia as diagnosed by extended needle biopsies.

OBJECTIVE: To examine the results of the clinical management of patients with high-grade prostatic intraepithelial neoplasia (PIN), as diagnosed by extended needle biopsies. PATIENTS AND METHODS: The clinical data were reviewed from a cohort of 387 men who underwent > or = 10 core prostate needle biopsies between 1 January 1996 and 31 December 1997 by one urologist (W.C.D.). Two study groups were identified; the first comprised 47 patients with only high-grade PIN and the second was a control group of 137 patients with only benign findings on their biopsies. Those patients with cancer, atypia or a prostatic biopsy with fewer than 10 cores were excluded. The clinical and histological data were evaluated. The criteria for re-biopsy were two successive increases in prostate specific antigen (PSA) level or any change in the findings on digital rectal examination (DRE). All patients were monitored at 6-12 month intervals. RESULTS: Of the 387 patients, 46% had normal findings, 5.2% had atypia, 12.6% had PIN alone, 15 (3.9%) had PIN plus atypia, 6.7% had PIN plus cancer and 32.3% had cancer. There was no significant difference between the PIN and control groups in age, DRE, PSA level, prostate size (by ultrasonography), free testosterone level, number of the cores and time of follow-up (median 34.8 and 36.6 months for the PIN and control groups, respectively). Of the PIN and control groups, 21 (45%) and 43 (31%) respectively had at least one re-biopsy. Five patients (24%) in the PIN and one (2.3%) in the control group developed cancer (P = 0.0124). All these patients had organ-confined disease and were found to have either Gleason scores 3 + 3 or 3 + 4 on surgical specimens. There was no correlation between the original location of PIN and the location of subsequent malignancy. CONCLUSIONS: Patients with one set of extended needle biopsies with high-grade PIN should be followed clinically every 6-12 months, and it may be safe to reserve repeat biopsy for those with changes in PSA level and/or in the DRE.

Aged↗
PubMed2006

Current prostate biopsy interpretation: criteria for cancer, atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, and use of immunostains.

CONTEXT: The past decade has brought major changes in prostate biopsy sampling, interpretation, and reporting. OBJECTIVE: To summarize current information on diagnostic decision making, Gleason grading, "atypical" diagnoses, and use of immunostaining. DATA SOURCES: Pertinent literature from 1985 to 2005 is reviewed, emphasizing recent findings. CONCLUSIONS: Diagnosis begins by evaluating a focus of atypical single-cell layer lined acini according to the 3 minimal diagnostic criteria for cancer: an infiltrative pattern, nuclear enlargement and hyperchromasia, and prominent nucleoli. The Gleason score and linear extent or percent of each core containing cancer should be reported. Atypical small acinar proliferation suspicious for malignancy designates foci that have either qualitative or quantitative limitations in atypia precluding a definite cancer diagnosis. It has about a 3% incidence as an isolated finding. Contemporary studies indicate a 39% predictive value for cancer on repeat biopsy. Isolated high-grade prostatic intraepithelial neoplasia has a 3% to 14% incidence and predicts cancer on repeat biopsy in 23% of cases. Immunostaining for a marker of benign prostate (cytoplasmic keratin 34betaE12 or nuclear p63) and a marker of cancer (alpha-methylacyl coA racemase, clone P504S) may or may not resolve atypical small acinar proliferation diagnoses. Performance of 34betaE12 and P504S immunostains resolved 76% of atypical small acinar proliferation diagnoses per consensus of 3 urologic pathologists studied; a technical limitation is preservation of the focus in question on the levels used for immunostaining.

Biomarkers, Tumor↗
PubMed2006

Is high-grade prostatic intraepithelial neoplasia on needle biopsy different in an Asian population: a clinicopathologic study performed in Singapore.

OBJECTIVES: To evaluate the incidence, pathologic findings, and follow-up of high-grade prostatic intraepithelial neoplasia (HGPIN) in a series of prostate core biopsies from Singaporean men. METHODS: We studied isolated HGPIN diagnosed on prostate core biopsies and the incidence of cancer discovered in men who had undergone repeat biopsies from 1999 to 2003 at the Department of Pathology, Singapore General Hospital. RESULTS: Of 1219 men undergoing prostate needle biopsy, 56 (4.6%) had isolated HGPIN. Most cases affected a single prostate core (44 cases, 78.6%). Twenty-nine men (51.8%) underwent repeat biopsies. Cancer was discovered in 7 (24.1%) of the 29 men within two repeat biopsies. CONCLUSIONS: The incidence of isolated HGPIN on prostate needle core biopsies in Asian men, as well as the likelihood of subsequent cancer detection, are comparable to the rates reported for Western populations. The relatively low yield of cancer detection on repeat biopsy supports the need to re-evaluate recommendations for rebiopsy strategies.

Aged↗
PubMed1996

Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha-reductase inhibitor (finasteride). A methodologic approach.

OBJECTIVE: To develop a methodology applicable to the morphologic study of the efficacy of finasteride on prostatic intraepithelial neoplasia (PIN), a putative precursor of prostate cancer. STUDY DESIGN: Three PIN foci were reviewed in two simple prostatectomy specimens from patients with clinical diagnoses of benign prostatic hyperplasia and treated with finasteride for six months. The feasibility of PIN diagnosis and grading based on "diagnostic distance" was investigated. It is a measure of the "extent" to which the observed features are different from those of the untreated prototypes representing the following diagnostic categories: normal prostate, low and high grade PIN and prostatic adenocarcinoma with a cribriform or large acinar pattern. Uncertainty in the PIN diagnosis and grading was dealt with by means of a Bayesian belief network (BBN). RESULTS: The distance measure values of the three PIN foci from the prototype of untreated, nonneoplastic prostate were 9, 7 and 8, respectively, in relative, arbitrary units. Their distance from the two prostate cancer patterns (large acinar and cribriform) was as high as 8-10. The distance of these foci from either low or high grade PIN were as low as 5, 3 and 2, and 3, 5 and 4, respectively. BBN produced the highest belief values for PIN, thus confirming the morphology-based and diagnostic distance-supported diagnosis; however, the belief values were low for both grades. CONCLUSION: The results provided by BBN analyses and diagnostic distance measures support the conclusion that this methodology is applicable to assessing the efficacy of finasteride treatment of PIN.

5-alpha Reductase Inhibitors↗
PubMed2005

High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation: predictive value for cancer in current practice.

In earlier studies, prostate cancer (PCa) has been reported to appear in 21% to 48% of subsequent biopsies for isolated high-grade prostatic intraepithelial neoplasia (PIN) and in 34% to 60% for isolated atypical small acinar proliferation suspicious for, but not diagnostic of, malignancy (ASAP). We report results of follow-up biopsies in a recent cohort of community practice patients who underwent biopsy for PSA abnormalities. The study group consisted of 336 men with initial diagnoses of PIN (n = 204), ASAP (n = 78), or both lesions (n = 54) who underwent at least one repeat biopsy. Mean follow-up intervals in months were 6.0 for PIN, 3.8 for ASAP, and 4.9 for PIN/ASAP. Follow-up PCa detection rates were 23%, 37%, and 33%, respectively. The predictive value of ASAP was significantly higher than that for PIN (P = 0.0188). In 23 PIN studies with chronologic midpoints in the early 1990s, follow-up PCa was detected in a mean of 36% of cases, whereas this value was 21% after the year 2000. In 13 ASAP studies, mean PCa detection on follow-up was 45% until 1996 and 39% from 1997 to present. PIN/ASAP predicted PCa in 33% of cases in our study, similar to ASAP alone (P = 0.65) and had a mean predictive value of 44% in the literature. Factors that may account for the decline in PIN predictive values include: 1) extended biopsy techniques that yield higher rates of initial cancer detection, 2) lower detection rate for the remaining small cancers that may accompany PIN, and 3) remaining PIN cases may lack concomitant cancer.

Aged↗
PubMed1996

Androgen receptors in untreated and treated prostatic intraepithelial neoplasia.

OBJECTIVES: The effect of androgen deprivation therapy on the expression of androgen receptors (AR) and the proliferation-associated MIB-1 antigen in prostatic intraepithelial neoplasia (PIN) was investigated. METHODS: Immunohistochemistry was performed on tissue sections of prostatectomy specimens of patients with prostate cancer who either were not treated prior to surgery or received androgen blockade therapy for 3 months. Immunohistochemistry on slides, selected for the presence of PIN was performed with an AR-specific monoclonal antibody and MIB-1 using a microwave antigen-retrieval method. RESULTS: AR expression was present in a majority of cells in PIN of both untreated and treated prostatectomy specimens. In addition, a proportion of normal prostatic glandular cells retained AR expression. The basal cells in both untreated and treated PIN did not express AR. MIB-1-positive cells were identified in PIN of untreated and treated cases. CONCLUSIONS: PIN lesions that persist after 3 months of androgen deprivation therapy continue to express AR and may therefore retain the potential to expand after cessation of this therapy.

Androgen Antagonists↗
PubMed2000

Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: correlation with grade and expression in high-grade prostatic intraepithelial neoplasia.

Arachidonic acid (AA) metabolites are implicated in the oncogenesis of several tumors, including prostate cancer. 15-Lipoxygenase-2 (15-LOX-2) is a novel AA-metabolizing enzyme with a limited tissue distribution, which includes prostate, lung, skin, and cornea. Previous studies have shown that 15-LOX-2 is present in benign prostate secretory cells and reduced in prostate adenocarcinoma and that production of the 15-LOX-2 metabolite 15S-hydroxyeicosatetraenoic acid is reduced in malignant compared with benign prostate. The objective of this study was to determine the frequency with which 15-LOX-2 immunostaining is reduced in prostate carcinoma and to correlate reduced expression with tumor differentiation (grade) and other pathologic parameters in radical prostatectomy specimens. Paraffin immunoperoxidase with a polyclonal antibody specific for 15-LOX-2 was performed on tumors and benign portions from 70 cases, and the percentage of tumor immunostaining for 15-LOX-2 was assessed. Whereas uniform 15-LOX-2 immunostaining was observed in secretory cells of benign glands, it was markedly reduced or absent in most adenocarcinomas: 23 of 70 tumors showed completely absent 15-LOX-2 immunostaining, and 45 of 70 cases showed negative immunostaining in more than 50% of the tumor. The extent of reduced 15-LOX-2 immunostaining correlated with tumor differentiation, with retained expression particularly in Gleason score 5 tumors versus a significant reduction of 15-LOX-2 in higher-grade tumors (mean +/- SD tumor 15-LOX-2 positive: Gleason score 5 = 67%+/-30%, Gleason score 6 = 16%+/-30%, Gleason score 7 = 23%+/-28%, Gleason score > or =8 = 41%+/-46%). In 16 cases with multifocal tumors or different foci of the same tumor with different grades, the higher-grade foci had significantly reduced 15-LOX-2 expression compared with the lower-grade foci. In peripheral zone tumors without complete loss of 15-LOX-2 expression, there was a significant inverse relationship between 15-LOX-2 immunostaining and tumor volume. There was not a significant correlation between 15-LOX-2 immunostaining and serum PSA or pathologic stage. In a subset of 27 cases, 15-LOX-2 expression in high-grade prostatic intraepithelial neoplasia (HGPIN) glands was significantly reduced compared with benign glands. These data show that in contrast to the uniform expression of 15-LOX-2 in differentiated secretory cells of benign prostate, reduced 15-LOX-2 is a common alteration in prostate carcinoma, and this correlates with tumor cell differentiation. That reduced expression is seen in HGPIN suggests that this may be an early alteration in carcinoma development.

Adenocarcinoma↗
PubMed2006

Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care.

PURPOSE: We identified information critical for patient treatment on prostate needle biopsies diagnosed with prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma. MATERIALS AND METHODS: A search was performed using the MEDLINE database and referenced lists of relevant studies to obtain articles addressing the significance of finding PIN or atypical foci suspicious for carcinoma on needle biopsy. RESULTS: There were certain results concerning PIN. 1) Low grade PIN should not be documented in pathology reports due to poor interobserver reproducibility and a relatively low risk of cancer following re-biopsy. 2) The expected incidence of HGPIN on needle biopsy is between 5% and 8%. 3) Although the diagnosis of HGPIN is subjective, interobserver reproducibility for its diagnosis is fairly high among urological pathologists, and yet only moderate among pathologists without special expertise in prostate pathology. 4) The median risk recorded in the literature for cancer following the diagnosis of HGPIN on needle biopsy is 24.1%, which is not much higher than the risk reported in the literature for repeat biopsy following a benign diagnosis. 5) The majority of publications that compared the risk of cancer in the same study following a needle biopsy diagnosis of HGPIN to the risk of cancer following a benign diagnosis on needle biopsy show no differences between the 2 groups. 6) Clinical and pathological parameters do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. 7) A major factor contributing to the decreased incidence of cancer following a diagnosis of HGPIN on needle biopsy in the contemporary era is related to increased needle biopsy core sampling, which detects many associated cancers on initial biopsy, such that re-biopsy, even with good sampling, does not detect many additional cancers. 8) It is recommended that men do not need routine repeat needle biopsy within the first year following the diagnosis of HGPIN, while further studies are needed to confirm whether routine repeat biopsies should be performed several years following a HGPIN diagnosis on needle biopsy. There were certain results concerning atypical glands suspicious for carcinoma. 1) An average of 5% of needle biopsy pathology reports are diagnosed as atypical glands suspicious for carcinoma. 2) Cases diagnosed as atypical have the highest likelihood of being changed upon expert review and urologists should consider sending such cases for consultation in an attempt to resolve the diagnosis as definitively benign or malignant before subjecting the patient to repeat biopsy. 3) Ancillary techniques using basal cell markers and AMACR (alpha-methyl-acyl-coenzyme A racemase) can decrease the number of atypical diagnoses, and yet one must use these techniques with caution since there are numerous false-positive and false-negative results. 4) The average risk of cancer following an atypical diagnosis is approximately 40%. 5) Clinical and pathological parameters do not help predict which men with an atypical diagnosis have cancer on repeat biopsy. 6) Repeat biopsy should include increased sampling of the initial atypical site, and adjacent ipsilateral and contralateral sites with routine sampling of all sextant sites. Therefore, it is critical for urologists to submit needle biopsy specimens in a manner in which the sextant location of each core can be determined. 7) All men with an atypical diagnosis need re-biopsy within 3 to 6 months. CONCLUSIONS: It is critical for urologists to distinguish between a diagnosis of HGPIN and that of atypical foci suspicious for cancer on needle biopsy. These 2 entities indicate different risks of carcinoma on re-biopsy and different recommendations for followup.

Biopsy, Needle↗
PubMed1999

Cell proliferation, apoptosis, oncogene, and tumor suppressor gene status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer.

There is scant information on the cell proliferation, apoptosis, oncogenes, and tumor suppressor genes status in adenosis. Forty-eight foci of adenosis were studied with immunohistochemistry for MIB-1; c-erbB-2, c-erbB-3, bcl-2 oncogenes; and p53. To evaluate apoptosis, the TdT dUTP nick end labeling (TUNEL) method was applied. Results were compared with the same studies on benign prostatic hyperplasia (BPH) (n = 20), low-grade prostatic intraepithelial neoplasia (PIN) (n = 10); high-grade PIN (n = 20), Gleason sum 2 to 6 cancer (n = 16); and Gleason sum 7 to 10 cancer (n = 22). MIB-1 proliferation index was lowest in BPH, followed by adenosis, low-grade prostatic intraepithelial neoplasia (PIN), low-grade cancer, high-grade PIN, and high-grade cancer. The apoptotic rate was generally low in all groups, although it was higher in PIN and cancer. In BPH and adenosis, bcl-2 was absent in luminal cells. In low- and high-grade PIN, both basal and luminal cells expressed bcl-2, whereas in cancer, expression was found in only 1 case (3%). C-erbB-2 showed absent or low values for cancer and adenosis, whereas it was commonly expressed in BPH and low- and high-grade PIN. Low expression in adenosis was also found with c-erbB-3 (6%) compared with all other groups. Expression of p53 was confined to cancer. Despite a significantly higher proliferation index rate compared with BPH, adenosis showed a markedly lower proliferating index when compared with low-grade PIN, high-grade PIN, and cancer. Expression of the oncogenes c-erbB-2 and cerbB-3 was very low in adenosis, and the staining pattern for bcl-2 was similar to that of BPH. These results provide additional evidence to that of prior studies that adenosis is a histological small acinar proliferation more akin to BPH than high-grade PIN or adenocarcinoma.

Adenocarcinoma↗
PubMed2004

Can the number of cores with high-grade prostate intraepithelial neoplasia predict cancer in men who undergo repeat biopsy?

OBJECTIVES: To evaluate whether the presence of, or the number of cores containing, high-grade prostatic intraepithelial neoplasia (PIN) found in men who underwent initial extended multisite biopsy could predict which men would have prostate cancer on subsequent repeat biopsies. METHODS: Between June 1997 and January 2003, 1086 men underwent initial prostate biopsy for early detection of prostate cancer using an extended multisite biopsy scheme. Of these, 175 men without cancer underwent at least one repeat biopsy (range one to three; median interval between biopsies, 3 months). Among these 175 patients, 47 had high-grade PIN on initial biopsy. RESULTS: The initial extended biopsy identified cancer in 33.8% (367 of 1086) and high-grade PIN in 20.8% (226 of 1086). The incidence of high-grade PIN only in patients found to have cancer on initial biopsy was 29.7% (109 of 367). The presence of high-grade PIN was associated with concurrent prostate cancer at the initial biopsy (P <0.0001). Overall, repeat biopsy identified cancer in 18.3% of the 175 men. Of the 47 men with high-grade PIN, 5 (10.6%) were found to have cancer on repeat biopsy. The number of biopsy specimens positive for high-grade PIN on initial biopsy was not associated with the likelihood of prostate cancer on repeat biopsy. Multivariate logistic regression analysis showed that neither the presence of high-grade PIN nor the number of cores containing high-grade PIN on initial biopsy were predictors for prostate cancer on repeat biopsy. CONCLUSIONS: The number of cores positive for high-grade PIN was not predictive for cancer on repeat biopsy.

Adenocarcinoma↗
PubMed2000

Foamy gland high-grade prostatic intraepithelial neoplasia.

A 60-year-old man underwent radical prostatectomy for biopsy-proved adenocarcinoma of the prostate. Histologic examination of the entirely embedded prostatectomy specimen revealed extensive ordinary adenocarcinoma, Gleason's grade 3 + 3 = 6, involving both sides of the gland, and extending into extraprostatic soft tissue at the left base. Adjacent to the carcinoma, and separately, extensive high-grade prostatic intraepithelial neoplasia (PIN) was identified, much of which showed bland nuclei and abundant xanthomatous cytoplasm, identical morphologically to that seen in foamy gland prostate carcinoma. However, unlike foamy gland carcinoma, the foamy glands in the current patient were large, showed papillary infolding, and were associated with a discontinuous layer of basal cells, demonstrated by immunostaining for high-molecular weight cytokeratin. No invasive foamy gland carcinoma was identified in the prostatectomy specimen. Immunostains for Ki-67 showed an increased proliferation rate in foamy high-grade PIN glands when compared with adjacent benign glands. Review of additional outside biopsy material revealed foamy gland high-grade PIN on four of seven needle cores, two of which showed no carcinoma. This patient demonstrates a new subtype of high-grade PIN that is difficult to recognize on needle biopsy. It is important to distinguish foamy gland high-grade PIN from its infiltrating counterpart, and it is critical to recognize because of the association of high-grade PIN with prostate carcinoma.

Adenocarcinoma↗
PubMed1998

Downregulation of the beta4 integrin subunit in prostatic carcinoma and prostatic intraepithelial neoplasia.

Integrins are adhesion receptors thought to be important in the process of cancer cell invasion and metastasis. Unlike other integrins, which attach a cell to extracellular matrix molecules, the alpha6beta4 integrin participates in the formation of hemidesmosomes, attaching epithelial cells to the basement membrane. Investigations of the alpha6beta4 integrin in human prostatic carcinoma have yielded conflicting results and have been primarily qualitative rather than quantitative. Expression of the beta4 integrin subunit was determined using rat monoclonal antibody 439-9B and image analysis in regions of benign prostatic epithelium (BPE), high-grade prostatic intraepithelial neoplasia (PIN), and prostatic carcinoma (CaP) in 38 patients treated by radical prostatectomy for clinically localized CaP. The beta4 integrin subunit was significantly downregulated in CaP compared with BPE; PIN stained intermediate in intensity between BPE and CaP. Thirty-four of 35 patients showed downregulation of the beta4 integrin subunit, and all 15 patients with PIN had downregulation of beta4 in PIN as compared with BPE. Degree of downregulation of the beta4 integrin subunit did not add prognostic significance to the information present at initial biopsy (age, clinical stage, clinical grade, and serum prostate-specific antigen level). There was no correlation between intensity of staining of CaP, absolute change in staining, or percent loss of beta4 integrin subunit staining with age, pathological stage, or Gleason's score. Downregulation of the beta4 integrin in CaP and PIN compared with BPE may be correlated with neoplastic transformation of the prostate and loss of hemidesmosomes or basal epithelial cells.

Aged↗