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Results for “Prostatic Intraepithelial Neoplasia”

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PubMed1995

Allelic loss on chromosome 8p12-21 in microdissected prostatic intraepithelial neoplasia.

The development and progression of human prostate cancer is associated with genetic abnormalities in tumor cells. Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mechanism of gene alteration in prostatic neoplasms. In this study we examined allelic loss on chromosome 8p12-21 in microdissected samples of normal prostatic epithelium, high grade prostatic intraepithelial neoplasia (PIN), and invasive prostate carcinoma from the same patients. Tissue microdissection under direct microscopic visualization procures pure populations of cells of interest, including small lesions such as PIN. Among 30 patients with concomitant cancer and PIN, we found loss of heterozygosity on chromosome 8p12-21 in 63% (34 of 54) of foci of PIN examined and 90.6% (29 of 32) of tumors, suggesting that abnormalities on chromosome 8p12-21 may be important in the early stages of prostatic carcinoma development. Several cases in which multiple foci of PIN from the same patient were sampled showed different patterns of allelic loss. Fifty-five % (16 of 29) of the prostate carcinomas contained a potential precursor PIN focus based on allelic loss pattern. Our results are consistent with the hypothesis that PIN arises multifocally within the prostate gland, and that a subset of these lesions progress to become carcinoma.

Alleles↗

PubMed2004

[Analysis of loss of heterozygosity on chromosome 10 in human prostate carcinoma and high grade prostatic intraepithelial neoplasia].

OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 10 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 of chromosome 10 was detected by PCR based microsatellite polymorphism analysis technique using 20 pairs of microsatellite primers in 16 samples of prostate carcinoma and 14 samples of high grade PIN. RESULTS: There were different frequencies of LOH in different loci on chromosome 10, varying from 0 to 46.2%, mainly located at 10q23 and 10q24-q25 regions. Seven samples of high grade PIN had LOH detected on chromosome 10. CONCLUSION: There were high frequency of LOH regions on chromosome 10 of prostate carcinoma. The rate of LOH in high grade PIN was much lower than that in prostate carcinoma. PTEN and MXI1 were two candidate tumor suppressor genes on 10q23 and 10q24-q25. They may be potentially involved in the initiation and progression of prostate carcinoma.

Aged↗

PubMed1996

Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations.

The progression of prostatic intraepithelial neoplasia (PIN) to invasive prostate carcinoma has been analyzed in the C3(1)/T(AG) transgenic mouse model and appears very similar to the process proposed to occur in humans. PIN lesions in these transgenic mice histologically resemble those found in human PIN. Low-grade PIN was observed in the ventral and dorsolateral lobes at 2 months of age, whereas high-grade PIN was found in both lobes by 5 months of age. A progressive increase in the number of PIN lesions was observed with age. Prostate carcinomas, which appeared to arise from PIN lesions, were found by 7 months of age in the ventral lobe and 11 months of age in the dorsolateral lobe. Expression of T(AG) mRNA and protein in these lesions correlated with the development of PIN and carcinomas, as did the overexpression of p53 protein. Apoptosis levels were quite low in normal epithelial cells, moderate in low-grade PIN, and high in high-grade PIN and carcinomas. Levels of expression of proliferating cell nuclear antigen correlated with the degree of severity of the prostate lesions. Eighteen % of PIN lesions were found to already harbor Ha-ras mutations, whereas 33% of carcinomas showed various mutations in Ha-ras, Ki-ras, and/or p53. Mutations in Ha-ras may, therefore, be an early event in a significant portion of PIN lesions. Because high-grade PIN showed many characteristics similar to those observed in carcinomas and high-grade PIN was often found contiguous to carcinomas, we conclude that high-grade PIN is a precursor lesion of prostate carcinoma in this transgenic model. These transgenic mice will be useful to study mechanisms responsible for the progression of invasive carcinomas from PIN precursor lesions, as may occur during the development of prostate cancer in humans.

Animals↗

PubMed1996

Follow-up of prostatic intraepithelial neoplasia.

Biopsy or fine-needle aspiration cytology are the only appropriate methods for detection of prostatic intraepithelial neoplasia (PIN). PIN has been suggested to be a principal precursor of invasive carcinoma of the prostate. Most reports on an association of PIN and invasive prostatic cancer have a follow-up of less than 1 year, indicating that the successively diagnosed cancer most probably was present at the time of diagnosis of PIN. The natural history of PIN is unknown and detection of PIN should therefore not influence therapeutic decisions. If coexistent carcinoma is not found, close surveillance is recommended to identify a possible subsequent cancer at an early stage. Follow-up examinations should be performed at 6-month intervals for 2 years and thereafter annually.

Biopsy, Needle↗

PubMed1998

Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia. Relationship to pathologic parameters, volume and spatial distribution of carcinoma of the prostate.

OBJECTIVE: To summarize studies that have investigated the morphologic, spatial and volumetric relationship between prostate cancer and its putative precursors, high grade prostatic intraepithelial neoplasia (HGPIN) and atypical adenomatous hyperplasia (AAH). METHODS: Studies addressing the relationship between morphologic parameters of prostate cancer (i.e., stage, grade, volume and anatomic distribution) and both HGPIN and AAH are reviewed. Similar data based on our institutional experience with surgical and autopsy series of step-sectioned, totally embedded prostate glands are also presented. RESULTS: Most investigators have demonstrated significant associations between HGPIN and carcinoma in terms of coexistence, "zonal" origin and physical proximity. The two lesions have a high tendency to be present simultaneously; both originate predominantly in the peripheral zone and are often found within the same microscopic field. Reports on the relationship between HGPIN and the stage of prostate cancer are less consistent, and the associations of this lesion with cancer grade and volume are exceedingly complex. HGPIN appears to be associated with moderately to poorly differentiated, smaller, often-multifocal tumors and is less frequent in large, high grade cancers. There are data suggesting a trend-of a reciprocal relationship between more extensive and diffuse HGPIN and large-volume prostate cancers. Conversely, there is a wide spectrum of volume distribution of the two lesions in glands harboring smaller tumors. Similar data concerning AAH are limited. CONCLUSION: There are strong and consistent data supporting various aspects of the morphologic associations between HGPIN and prostate cancer. The indications that glands harboring larger tumors tend to contain less extensive HGPIN could raise the hypothesis that as carcinoma becomes larger, it may replace areas of the gland previously occupied by HGPIN. Alternatively, prostate cancer can evolve from ducts with HGPIN and gradually overgrow their precursor. There is a relative dearth of similar information concerning AAH.

Adenoma↗

PubMed2002

Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia.

The homeodomain-containing transcription factor NKX3.1 is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. Loss of NKX3.1 protein expression is common in human prostate carcinomas and prostatic intraepithelial neoplasia (PIN) lesions and correlates with tumor progression. Disruption of the murine Nkx3.1 gene results in defects in prostate branching morphogenesis, secretions, and growth. To more closely mimic the pattern of NKX3.1 loss that occurs in human prostate tumors, we have used Cre- and loxP-mediated recombination to delete the Nkx3.1 gene in the prostates of adult transgenic mice. Conditional deletion of one or both alleles of Nkx3.1 leads to the development of preinvasive lesions that resemble PIN. The pattern of expression of several biomarkers (Ki-67, E-cadherin, and high-molecular-weight cytokeratins) in these PIN lesions resembled that observed in human cases of PIN. Furthermore, PIN foci in mice with conditional deletion of a single Nkx3.1 allele lose expression of the wild-type allele. Our results support the role of NKX3.1 as a prostate tumor suppressor and indicate a role for this gene in tumor initiation.

Animals↗

PubMed2004

Expression of ezrin in prostatic intraepithelial neoplasia.

OBJECTIVES: To study the protein expression and gene copy number of ezrin in a set of high-grade prostatic intraepithelial neoplasia (HGPIN) samples with concomitant prostate cancer. Ezrin is a cytoskeleton linker protein that is actively involved in regulating the growth and metastatic capacity of cancer cells. METHODS: Nineteen HGPIN samples obtained from radical prostatectomy specimens were used for the study. Among them, 13 samples also contained invasive prostate cancer. The expression of ezrin was studied by immunohistochemistry. The same samples were also used for fluorescence in situ hybridization to study the gene copy number of ezrin. RESULTS: Immunoreactivity for ezrin was absent or weak in benign prostatic epithelial cells. Weak or moderate immunostaining was detected in 11 of 13 prostate cancer specimens. However, the immunostaining was moderate or strong in all HGPIN samples. In addition, whenever HGPIN and prostate cancer were found in the same sample, the staining was always more intense in the HGPIN cells than in the cancer cells. No alteration was found in the gene copy number detected by fluorescence in situ hybridization. CONCLUSIONS: We have shown that ezrin is overexpressed in HGPIN and prostate cancer compared with adjacent benign prostatic epithelium. In addition, HGPIN has a greater expression level of ezrin compared with that of prostate cancer. Our results indicate that aberrant expression of ezrin might be involved in the pathogenesis of prostate cancer, and ezrin expression may be useful for the diagnosis of HGPIN.

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↗

PubMed2002

Prostaglandin E(2) stimulates prostatic intraepithelial neoplasia cell growth through activation of the interleukin-6/GP130/STAT-3 signaling pathway.

Cyclooxygenase (COX)-2 expression and prostaglandin E(2) (PGE(2)) secretion are increased in prostatic intraepithelial neoplasia (PIN) and prostate cancer. PGE(2) biosynthesis by cyclooxygenase (COX)-2 plays a pivotal role in inflammation and carcinogenesis. One of the critical proinflammatory cytokines in the prostate is interleukin-6 (IL-6). We hypothesized that increased expression of COX-2, with resultant increased levels of PGE(2) in human PIN cells, activates the IL-6 signaling pathway. We demonstrate an autocrine upregulation of PGE(2) mediated by IL-6 in a human PIN cell line. We further demonstrate that PGE(2) stimulates soluble IL-6 receptor (sIL-6R) release, gp130 dimerization, Stat-3 protein phosphorylation, and DNA binding activity. These events, induced by PGE(2), lead to increased PIN cell growth. Treatment of PIN cells with a selective COX-2 inhibitor decreases cell growth. Finally, PGE(2)-stimulated PIN cell growth was abrogated by the addition of IL-6 neutralizing antibodies. These data provide mechanistic evidence that increased expression of COX-2/PGE(2) contributes to prostate cancer development and progression via activation of the IL-6 signaling pathway.

Antigens, CD↗

PubMed1999

Biologic markers in prostatic intraepithelial neoplasia: immunohistochemical and cytogenetic analyses.

OBJECTIVE: We evaluated the biological properties of High-grade prostatic intraepithelial neoplasia (PIN) by immunohistochemistry and fluorescence in situ hybridization (FISH) analysis in relation to normal tissue and carcinoma lesions. MATERIALS AND METHODS: Immunohistochemical staining and FISH were performed on 23 formalin-fixed radical prostatectomy specimens taken from patients with PIN. Assays were performed using MIB-1, chromogranin A (CGA) and an anti-androgen receptor antibody (AR). A centromere probe for chromosome 8 was used to test for aneuploidy. RESULTS: The MIB-1 index of cancerous specimens (16.2 +/- 10.5%) was significantly higher than that of benign (1.9 +/- 1.6%, p < 0.0001) or PIN (4.0 +/- 4.5%, p < 0.0001) specimens. The percentage of CGA positive cells was significantly lower in normal tissue (1.2 +/- 1.8%) than in PIN (3.5 +/- 2.9%, p = 0.012) or carcinoma (5.4 +/- 4.9%, p = 0.005) lesions. Positive staining for AR was consistently observed in the nuclei of both benign and malignant epithelial cells, but positive cytoplasmic staining was also seen in PIN epithelial cells. No significant difference in FISH detected anomalies were found between PIN and carcinoma specimens. CONCLUSIONS: Our studies concerning proliferative activity, NE differentiation and chromosomal anomalies of prostatic specimens support the hypothesis that PIN is a biologically intermediate stage in the pathogenesis of prostatic carcinoma. The cellular distribution of AR was altered in PIN cells, but the role of AR in PIN is not yet clear.

Aged↗

PubMed2005

Should high-grade prostatic intraepithelial neoplasia change our approach to infravesical obstruction?

OBJECTIVES: To investigate whether coexistence of high-grade prostatic intraepithelial neoplasia (HPIN) should change our therapeutic approach to infravesical obstruction. MATERIAL AND METHODS: Of 505 patients who underwent sextant transrectal ultrasonography (TRUS)-guided prostate biopsy, 65 (12.8%) had HPIN and 29 of them underwent prostatectomy (23 transurethral resection of prostate (TURP), 6 open) due to obstructive urinary symptoms. Patients without carcinoma were followed up with semiannual prostate-specific antigen (PSA) and digital rectal examination. After a follow-up of 24.8 +/- 11.0 months, 19 of 29 patients who accepted our call had another sextant biopsy. RESULTS: Mean age and initial mean PSA values of 29 patients were 67.6 +/- 6.7 years and 9.26 +/- 5.91 ng/ml, respectively. The final pathological evaluation of the surgical specimens revealed 2 prostatic adenocarcinomas both in the TURP group. The remaining 27 (93.2%) patients were found to have benign prostatic hyperplasia (BPH) and their serum PSA levels declined from 9.26 +/- 5.91 to 4.59 +/- 2.0 ng/ml 3 months after prostatectomy. Of the 19 patients who had another biopsy with a mean PSA value of 4.06 +/- 4.61 ng/ml, 15 and 4 of them had BPH and HPIN respectively. CONCLUSIONS: Our preliminary data indicate that the presence of HPIN on TRUS-guided biopsies is not a factor to delay an indicated surgical intervention for infravesical obstruction.

Adenocarcinoma↗

PubMed2002

Prostatic intraepithelial neoplasia in genetically engineered mice.

Several mouse models of human prostate cancer were studied to identify and characterize potential precursor lesions containing foci of atypical epithelial cells. These lesions exhibit a sequence of changes suggesting progressive evolution toward malignancy. Based on these observations, a grading system is proposed to classify prostatic intraepithelial neoplasia (PIN) in genetically engineered mice (GEM). Four grades of GEM PIN are proposed based on their architecture, differentiation pattern, and degree of cytological atypia. PIN I lesions have one or two layers of atypical cells. PIN II has two or more layers of atypical cells. PIN III has large, pleomorphic nuclei with prominent nucleoli and the cells tend to involve the entire lumen with expansion of the duct outlines. PIN IV lesions contain atypical cells that fill the lumen and bulge focally into, and frequently compromise, the fibromuscular sheath. Within the same cohorts, the lower grade PINs first appear earlier than the higher grades. Morphometric and immunohistochemical analyses confirm progressive change. Although the malignant potential of PIN IV in mice has not been proven, GEM PIN is similar to human PIN. This PIN classification system is a first step toward a systematic evaluation of the biological potential of these lesions in GEM.

Animals↗

PubMed1998

Is prostatic intraepithelial neoplasia in the transition/central zone a true precursor of cancer? A long-term retrospective study in Norway.

Prostatic intraepithelial neoplasia (PIN) has been considered as a precursor of prostatic cancer. Few reports have dealt with the long-term follow-up of PIN lesions, and there is still a lack of proof that PIN is a true premalignant lesion. The objective of this study was to evaluate PIN in the transition/central zone as a marker for subsequent development of prostatic cancer. The PIN status of tissue specimens from 789 men without prostate cancer was determined in 508 transurethral resections and 281 transvesical prostatic enucleations. All slides were reviewed blind and independently by two pathologists. The patients were followed for an average of 11 years, and the incidence of subsequent cancer and cause-specific survival were analysed. Thirty-six cases of clinical prostatic cancer occurred among the cohort of 789 men through follow-up. No association between the presence of PIN in the transition/central zone and subsequent cancer development was found. There was also no difference in survival related to PIN status among the subsequent cancer patients.

Aged↗

PubMed1997

Prostatic intraepithelial neoplasia in surgical resections: relationship to coexistent adenocarcinoma and atypical adenomatous hyperplasia of the prostate.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is associated with coincident prostate carcinoma, and has been considered to be a precursor of prostate carcinoma. Most studies on PIN have been performed on total prostatectomy or core needle biopsy specimens. Few reports deal with the occurrence of PIN in consecutive surgical resections, which is the objective of the current study. METHODS: A total of 1135 nonselected surgical specimens from the prostate, examined during 1974 and 1975, underwent blind review by 2 experienced pathologists. There were 79 core needle biopsies, 731 transurethral resections of the prostate and 325 transvesical prostatic enucleations. The kappa coefficient for interobserver reproducibility was 0.66 for PIN and 0.86 for carcinoma. RESULTS: Grade 1 PIN was found in 9%, Grade 2 PIN in 32%, and Grade 3 PIN in 20% of the total cases. Atypical adenomatous hyperplasia (AAH) was found in 11% and adenocarcinoma in 27% of the cases. Grade 3 PIN was associated with coincident adenocarcinoma in 39% of the cases. The prevalence of carcinoma for cases with Grade 1 and 2 PIN did not exceed that of those with Grade 0 PIN. PIN was most commonly found in association with small carcinomas. The mean age of the entire group of patients was 70.0 years, and was 69.4 years for patients with PIN without coincident carcinoma. Patients with PIN and coincident carcinoma had a mean age of 71.7 years, similar to all PIN grades, but patients with carcinoma without PIN had the highest mean age, 73.3 years. CONCLUSIONS: PIN is a common histologic finding in tissues from prostatic resections. In this study, Grade 3 PIN was strongly associated with coincident carcinoma, but lower grade PIN was not. There was no association between PIN and AAH. Patients with PIN did not appear to have a higher mean age than corresponding patients without PIN.

Adenoma↗

PubMed2001

Effect of androgen deprivation therapy on prostatic intraepithelial neoplasia.

There is a marked decrease in the prevalence and extent of high-grade prostatic intraepithelial neoplasia (PIN) in men with prostate cancer after androgen deprivation therapy (ADT) when compared with untreated cases. Basal cell hyperplasia, cytoplasmic clearing, and prominent atrophy of benign acini, with decreased ratio of acini to stroma, accompany this decrease. These findings indicate that the benign and dysplastic prostatic epithelium is androgen dependent. In the normal prostatic epithelium, luminal secretory cells are more sensitive to the absence of androgen than basal cells, and the proliferative cells of high-grade PIN share this androgen sensitivity. The loss of some normal, hyperplastic, and dysplastic epithelial cells with ADT is probably because of acceleration of programmed single-cell death. Remarkably little is known about the comparative effect of different forms of chemical ADT on PIN and cancer, although there appears to be a limited and consistent repertoire of morphologic responses to all forms of this therapy. Conversely, blockade of 5alpha-reductase with finasteride has little or no effect on PIN (or benign epithelium and cancer), unlike other forms of ADT. A recent international consensus conference sponsored by the World Health Organization concluded that identification of high-grade PIN offered the possibility of chemoprevention with hormonal therapy to block the development of clinical cancer. Multiple chemoprevention trials are planned or under way to address this hypothesis.

Adenocarcinoma↗

PubMed1996

Influence of irradiation and androgen ablation on prostatic intraepithelial neoplasia.

OBJECTIVES: Although irradiation and endocrine therapy have been used in the treatment of prostatic carcinoma for several decades and the effects of such therapy on carcinoma and the normal prostate have been well described and although there is ample evidence linking prostatic intraepithelial neoplasia (PIN) to the origin of prostatic adenocarcinoma, there is little published information on the effect of such therapies on PIN. METHODS AND RESULTS: The extant literature on this subject is reviewed and analyzed. The literature on total androgen blockade is not extensive but adequate to draw conclusions. The literature on irradiation therapy is minimal and inadequate to draw definite conclusions. CONCLUSIONS: The available evidence indicates that the prevalence and extent of PIN in prostates that have been treated with endocrine therapy is reduced from what might otherwise be expected. Irradiation therapy may have little effect on the prevalence of PIN but might influence the extent of PIN.

Androgen Antagonists↗

PubMed2002

Central zone histology of the prostate: a mimicker of high-grade prostatic intraepithelial neoplasia.

The central zone (CZ) is located at the base of the prostate adjacent to the seminal vesicles. Its histology as a potential mimicker of high-grade prostatic intraepithelial neoplasia (PIN) has not been formally studied. Three groups were evaluated. Group 1 comprised 30 consecutive radical prostatectomy specimens assessed for the extent of CZ and of Roman arch and/or cribriform formation in the CZ. Group 2 comprised 100 consecutive cases of nonconsult prostate needle biopsies, screened in a random blinded fashion to identify CZ histology and the specificity of its identification on biopsy. Group 3 comprised 34 consult cases (1984 to the present) with CZ histology on needle biopsy. For group 1, the average maximum diameter of CZ histology was 5 mm. Two cases (6.7%) did not contain the classic features of CZ histology. The average amount of cribriform and/or Roman arch formation in the areas with CZ histology was 16.5%. In group 2, 10% of prostate needle biopsy cases had CZ histology. Of these, 80% were located on biopsy specimens designated as the base of the prostate, 10% were located in the base and midportion of the prostate, and 10% were located in the midportion of the prostate. For group 3, CZ histology occupied on average 32% of the involved core. The 2 most common histologic features were eosinophilic cytoplasm (97%) and location at the end of a core (97%). Other features were Roman arch formation (59%), a prominent basal cell layer (32%), cribriform formation (26%), and associated thick muscle bundles typical of bladder neck (24%). On average, cribriform and/or Roman arch formation occupied 22% of the CZ area seen on biopsy. Twenty-six of the consult cases were sent in with preliminary outside diagnoses. Of these, 21 (81%) were either PIN or atypical: 11 (42%) high-grade PIN, 7 (27%) PIN, and 3 (12%) atypical glands. Our findings show that CZ histology is distinctive, as seen in radical prostatectomy specimens. Less frequently it is found on needle biopsy, where the presence of Roman arch and/or cribriform formation mimics PIN. Recognition of the distinctive features of CZ histology (i.e., tall columnar cells with eosinophilic cytoplasm, prominent basal cell layer, and lack of cytologic atypia) can help avoid a misdiagnosis of PIN or "atypia" on needle biopsy.

Biopsy, Needle↗

PubMed1999

Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT.

Cultures from high grade prostatic intraepithelial neoplasia (HGPIN) have been established and immortalized by HPV-18 infection. The cultures were identified as PIN by Western blotting with anti-cytokeratin (34betaE12) and prostate specific antigen (PSA) antibodies. We examined the growth capabilities of the cultures in the presence of TGF-beta1, activin-A, follistatin (FS), androgens (DHEA, DHT) and several cytokines (IL-10, IL-2, IL-4). IL-10, FS, and DHT stimulated cell proliferation and colony forming ability, while the other cytokines and growth factors had no discernable effect. In addition, DHT and to a lesser extent IL-10 both stimulated PSA production. Activin-A blocked IL-10, FS, and DHT stimulated growth and PSA production. We interpret the data to mean that IL-10 induction of FS secretion (and FS binding of activin A) restores the normal growth capabilities of HGPIN cultures.

Activins↗