Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0282612 (PIN)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemistry with antibodies for high-molecular-weight cytokeratin labels basal cells and is used as an ancillary study in diagnosing prostate carcinoma, which reportedly lacks expression of high-molecular-weight cytokeratin. A recent report questioned the specificity of this marker, describing immunopositivity for high-molecular-weight cytokeratin in a small series of metastatic prostate cancer. We have also noted rare cases of prostate lesions on biopsy with typical histological features of adenocarcinoma showing immunopositivity for high-molecular-weight cytokeratin, either in tumor cells or in patchy cells with the morphology of basal cells. In some of these cases, it was difficult to distinguish cancer from out-pouching of high-grade prostatic intraepithelial neoplasia. To investigate whether prostate cancer cells express high-molecular-weight cytokeratin, we studied 100 cases of metastatic prostate carcinoma and 10 cases of prostate cancer invading the seminal vesicles from surgical specimens. Metastatic sites included regional lymph nodes (n = 67), bone (n = 19), and miscellaneous (n = 14). Cases with any positivity for high-molecular-weight cytokeratin antibody (34betaE12) were verified as being of prostatic origin with immunohistochemistry for prostate-specific antigen and prostate-specific acid phosphatase. Only four cases were detected positive for high-molecular-weight cytokeratin. In two cases (one metastasis, one seminal vesicle invasion) there was weakly diffuse positivity above background level. Two metastases in lymph nodes showed scattered strong staining of clusters of tumor cells, which represented <0.2% of tumor cells in the metastatic deposits. These positive cells did not have the morphology of basal cells. We conclude that prostate cancer, even high grade, only rarely expresses high-molecular-weight cytokeratin. This marker remains a very useful adjunct in the diagnosis of prostate cancer.
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PMID:Rare expression of high-molecular-weight cytokeratin in adenocarcinoma of the prostate gland: a study of 100 cases of metastatic and locally advanced prostate cancer. 998 40

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.
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PMID:Evolution of isolated high-grade prostate intraepithelial neoplasia in a Mediterranean patient population. 1032 12

Positive family history is a significant risk factor for prostate cancer. Improved knowledge of the epidemiology and molecular basis of hereditary prostate cancer has led to a need for counseling and clinical follow-up for men with a positive family history of prostate cancer. However, very little information is available on the efficacy of early screening procedures, such as serum prostate-specific antigen (PSA) measurements, in the management of genetically predisposed, high-risk individuals. In a nationwide study, we obtained family histories from 2099 Finnish prostate cancer patients and identified 302 families with two or more affected cases. Here, 209 asymptomatic 45-75-year-old males from these families were included in a study to determine the frequency of serum PSA positivity and the prevalence of subclinical prostate cancers. Serum PSA was elevated in 21 (10.0%) of these high-risk individuals. Seven prostate cancers (3.3%) and two high-grade prostatic intraepithelial neoplasia lesions were diagnosed, with three cancers occurring in men ages < or = 59 years. Men from prostate cancer families with an average age of onset of < 60 years had a significantly higher frequency of PSA positivity (28.6%, P = 0.01) as well as cancers (14.3%, P = 0.02) than those with a later age of onset. The results suggest that prostate cancer development in genetically predisposed individuals is preceded by a subclinical period when PSA detection is possible. Serum PSA screening may be particularly useful in men with a family history of early-onset prostate cancer.
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PMID:Detection of subclinical cancers by prostate-specific antigen screening in asymptomatic men from high-risk prostate cancer families. 1038 9

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer. The effect of radiation therapy (RT) on the prevalence of PIN is uncertain. We studied 86 patients who underwent salvage radical prostatectomy after irradiation failure at the Mayo Clinic. The prevalence, volume, multicentricity, spatial proximity to cancer, and architectural patterns of PIN were evaluated. High-grade PIN was identified in 53 (62%) of 86 prostatectomy specimens. Multiple architectural patterns were usually observed, including tufting in 87%, micropapillary in 66%, cribriform in 38%, and flat in 17%. The mean volume of PIN was 0.12 cm3 (range, 0.05-1.20 cm3). PIN was usually multicentric (70%), with a mean number of PIN foci of 2.5 (range, 1-10). Ninety-four percent of PIN foci were located within 2 mm of invasive cancer. There was no correlation between PIN and pathologic stage, surgical margin, tumor size, DNA ploidy, post-RT Gleason score, time interval from RT to biopsy-proven recurrence, postoperative prostate-specific antigen level, distant metastasis-free survival, or cancer-specific survival. Our examination of salvage radical prostatectomy specimens indicated that the prevalence and extent of PIN appeared to be reduced after RT compared to published studies of prostatectomies without prior RT.
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PMID:Prevalence and distribution of prostatic intraepithelial neoplasia in salvage radical prostatectomy specimens after radiation therapy. 1040 3

We reviewed 137 prostate sextant needle biopsies from 137 patients obtained at a median of 35.7 months after three-dimensional conformal external beam radiation therapy (3DCRT). Thirty-one patients (23%) received 3 months of androgen deprivation therapy (ADT) before 3DCRT. We also retrospectively reviewed and assigned a combined Gleason score to the pre-3DCRT needle biopsies (97 patients) or transurethral resection of the prostate gland (1 patient). High-molecular-weight cytokeratin (34betaE12) and prostate-specific antigen (PSA) immunohistochemistry was performed in select cases. After 3DCRT, histopathologic changes in benign prostate gland consisted of glandular atrophy, cytologic atypia, and basal cell prominence. The benign glands showed intensely positive reactions with antibodies to high-molecular-weight cytokeratin (34betaE12) and negative to weakly positive reactions to PSA. Paneth cell-like change was seen in 44 (32%) of the biopsies, mucinous metaplasia in 29 (21%), luminal blue-tinged mucinous secretions in 14 (10%), and squamous metaplasia in 8 (6%). The changes in benign prostate tissues were similar between patients treated with ADT and 3DCRT and those treated with 3DCRT alone. After 3DCRT, we recognized two histologic patterns of prostate cancer: (1) prostate cancer showing radiation therapy (RT)-related changes characterized by PSA-positive/34betaE12-negative poorly formed glands or individual cells with abundant clear to finely granular cytoplasm, and (2) prostate cancer showing no apparent RT effect. High-grade prostatic intraepithelial neoplasia (PIN) was seen in 12 post-3DCRT biopsies (8.8%). The use of neoadjuvant ADT had a significant impact on the results of post-RT biopsy. Of the 31 patients treated with neoadjuvant ADT and 3DCRT, 3 (10%) had post-3DCRT biopsies showing prostate cancer without RT effect compared to 44 of 106 men (41%) treated with 3DCRT alone (p = 0.004). Compared to the Gleason score pre-RT, the Gleason score of cancers showing no RT effect was the same in 25 patients (71%), +/-1 point in 8 patients (23%), and +2 points in 2 patients (6%). The mean combined Gleason score post-RT was slightly, although significantly, higher than that pre-RT (7.29 +/- 0.71 versus 7.00 +/- 0.59, p = 0.01). Serum PSA at the time of post-3DCRT biopsy correlated with biopsy results. Prostate cancer without therapy effect was seen in only one of 43 patients (2%) with a serum PSA level < or = 1 ng/ml compared to 46 of 94 patients (49%) with a PSA level > 1 ng/ml (p = 0.0001). After 3DCRT, benign prostate glands show profound histopathologic changes and may be confused with prostate cancer. The effects of 3DCRT on prostate cancer are variable, with some cases showing profound therapy-related changes and others showing no apparent therapy effect.
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PMID:Histopathologic effects of three-dimensional conformal external beam radiation therapy on benign and malignant prostate tissues. 1047 61

Proliferation in the setting of longstanding chronic inflammation appears to predispose to carcinoma in the liver, large bowel, urinary bladder, and gastric mucosa. Focal prostatic atrophy, which is associated with chronic inflammation, is highly proliferative (Ruska et al, Am J Surg Pathol 1998, 22:1073-1077); thus the focus of this study was to more fully characterize the phenotype of the atrophic cells to assess the feasibility of the proposal that they may be targets of neoplastic transformation. The pi-class glutathione S-transferase (GSTP1), a carcinogen-detoxifying enzyme, is not expressed in >90% of prostate carcinomas (CaPs). GSTP1 promoter hypermethylation, which appears to permanently silence transcription, is the most frequently detected genomic alteration in CaP (Lee et al, Proc Natl Acad Sci USA 1994, 91:11733-11737; >90% of cases). In high-grade prostatic intraepithelial neoplasia (PIN), this alteration is present in at least 70% of cases (Brooks et al, Cancer Epidemiol Biomarkers Prev, 1998, 7:531-536). Although normal-appearing prostate secretory cells rarely express GSTP1, they remain capable of expression, inasmuch as GSTP1 promoter hypermethylation is not detected in normal prostate. Fifty-five lesions from paraffin-embedded prostatectomy specimens (n = 42) were stained for GSTP1, using immunohistochemistry. Adjacent sections were stained for p27(Kip1), Ki-67, androgen receptor (AR), prostate-specific antigen (PSA), prostate-specific acid phosphatase (PSAP), Bcl-2, and basal cell-specific cytokeratins (34betaE12). With normal prostate epithelium as the internal standard, staining was scored for each marker in the atrophic epithelium. The lesions showed two cell types, basal cells staining positive for 34betaE12, and atrophic secretory-type cells staining weakly negative for 34betaE12. All lesions showed elevated levels of Bcl-2 in many of the secretory-type cells. All lesions had an elevated staining index for the proliferation marker Ki-67 in the secretory layer and decreased expression of p27(Kip1), a finding reminiscent of high-grade PIN (De Marzo et al, Am J Pathol 1998, 153:911-919). Consistent with partial secretory cell differentiation, the luminal cells showed weak to moderate staining for androgen receptor and the secretory proteins PSA and PSAP. All atrophic lesions showed elevated GSTP1 expression in many of the luminal secretory-type cells. Because all lesions are hyperproliferative, are associated with inflammation, and have the distinct morphological appearance recognized as prostatic atrophy, we suggest the term "proliferative inflammatory atrophy" (PIA). Elevated levels of GSTP1 may reflect its inducible nature in secretory cells, possibly in response to increased electrophile or oxidant stress. Elevated Bcl-2 expression may be responsible for the very low apoptotic rate in PIA and is consistent with the conclusion that PIA is a regenerative lesion. We discuss our proposal to integrate the atrophy and high-grade PIN hypotheses of prostate carcinogenesis by suggesting that atrophy may give rise to carcinoma either directly, as previously postulated, or indirectly by first developing into high-grade PIN.
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PMID:Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. 2017 14

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in a variety of biological events including interactions with galactose-containing glycoconjugates, cell proliferation, differentiation and apoptosis. Galectin-3 appears to intervene during tumor progression and altered expression patterns have been reported in a variety of malignancies. In our study, we have examined the expression of galectin-3 in a population of 145 prostate carcinoma samples using immunohistochemistry. We found that most of the non-tumoral prostatic glands exhibited moderate immunostaining for galectin-3 localized in both nucleus and cytoplasm. In prostatic cancer cells, galectin-3 was usually not expressed or decreased compared with the normal glands. Interestingly, when galectin-3 was detected in the cancer cells, it was consistently excluded from the nucleus and only present in the cytoplasmic compartment. The latter observation was also made for prostatic intraepithelial neoplasia (PIN) cells. Furthermore, we found that the levels of galectin-3 expression in the cancer cells were significantly associated with prostate-specific antigen (PSA) relapse in univariate analysis (p = 0.044). Cytoplasmic expression of galectin-3 in the carcinoma cells was an independent predictor of disease progression in multivariate analysis, after the pathological stage and the Gleason score. Our data demonstrate that galectin-3 is generally down-regulated in human prostate carcinoma cells, and consistently excluded from the nucleus. Interestingly, specific cytoplasmic expression of galectin-3 in a subset of lesions is associated with disease progression. These results suggest that galectin-3 might play anti-tumor activities when present in the nucleus, whereas it could favor tumor progression when expressed in the cytoplasm. Further studies should determine the exact role and mechanisms by which galectin-3 differentially affects cell behavior in the different locations where it is expressed.
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PMID:Alteration of the cytoplasmic/nuclear expression pattern of galectin-3 correlates with prostate carcinoma progression. 1095 11

The authors compared the influence of a conventional and an optimized submitting method of prostate core needle biopsy specimens on the frequency of cancer detected and the pathologic characteristics of the adenocarcinoma bearing biopsy specimens. The patients included were part of the prostate-specific antigen (PSA) screening program of Tyrol/Austria. Of the systematic core needle biopsy specimens from 500 unselected men obtained within 1 year from the Urological Department, University of Innsbruck, the core biopsy specimens of 250 cases were submitted conventionally, floating free in formalin-filled containers, whereas the biopsy specimens of the other 250 cases were stretched and orientated between 2 meshes in tissue cassettes at the time of biopsy before formalin fixation. On 136 cases diagnosed as adenocarcinoma the number and the length of cores as well as number of the cores involved by cancer and the tumor size were morphometrically determined. The diagnosis of benign prostatic hyperplasia, isolated high-grade prostatic intraepithelial neoplasia (PIN), atypical foci suspicious for cancer, and carcinoma was made in 66%, 5.6%, 4.8%, and 23.6% after conventional submission and in 61.6%, 6.4%, 1.2%, and 30.8% of the cases after optimized preembedding respectively. In the adenocarcinoma cases the optimizedly preembedded material showed higher mean total core length (126.5 mm versus 93.9 mm; P < .0001), a higher mean total tumor length (14.1 mm versus 8.6 mm; P = .01), and more cores involved by cancer (2.9 versus 2.4; P = .01) compared with the conventionally worked-up biopsy specimens. Optimized preembedding of core needle biopsy specimens in tissue cassettes could be quickly and routinely done by the assistance of the urologists at the time of biopsy. The significant improvement of the histologic yield of optimizedly preembedded prostatic needle biopsy specimens led to a higher frequency of cancer diagnosis, a reduction of cases with atypical foci suspicious for cancer and a significantly lower number of cases with only 1 core biopsy involved by cancer.
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PMID:Diagnostic effect of an improved preembedding method of prostate needle biopsy specimens. 1101 78

Rhesus monkeys were used to investigate the role of androgenic steroids and estradiol in the induction of hyperplastic changes in stromal and glandular prostate tissues. Adult male rhesus monkeys were procured from the wild and, after routine quarantine procedures, were randomly divided into 5 groups of 5 animals each. Gluteus maximus muscles were injected with 2.5 mg of androstenedione (Group II), 2.5 mg of dihydrotestosterone (DHT) or 0.25 mg of estradiol (Group II), 2.5 mg androstanediol (Diol; Group IV), or Diol in combination with 0.25 mg of estradiol (Group V). Group I consisted of untreated controls. Animals were injected with steroids 3 times a week for 2 years. Treatment with androstenedione (Group II) resulted in stromal hyperplasia in the caudal lobe and an increase in epithelial cell height in all zones except in the central zone of the caudal lobe. In monkeys treated with DHT and estradiol (Group III), stromal hyperplasia in both lobes, a decrease in tubular size, and degranulation and vacuolation of epithelial cells were noticed. Injection of Diol alone (Group IV) or in combination with estradiol (Group V) resulted in a widening of stroma in the central and peripheral zones of cranial and caudal lobes, whereas the tubular size decreased. Diol also induced epithelial cell hypercellularity in the central and peripheral zones of the caudal lobe and in the peripheral zone of the cranial lobe. Prostate-specific antigen levels in Group IV animals gradually increased from 6 months of treatment and were maximal after 18 months of injections. Serum estradiol levels increased to detectable levels in all groups except Group IV. Serum testosterone levels decreased to very low or undetectable levels in all groups, whereas prostate-specific acid phosphatase increased in all treated groups. Prolactin levels were elevated in all treated groups except in animals injected with androstenedione. These results indicate that repeated long-term injections of androstenedione or DHT and estradiol induced stromal hyperplasia, which may be an estrogen-related effect. Androstanediol-induced hypercellularity and stratification of glandular epithelium is comparable to human prostatic intraepithelial neoplasia. These results also suggest that the rhesus monkey is a suitable animal model for experimental induction of prostate diseases.
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PMID:Effects of long-term administration of androgens and estrogen on rhesus monkey prostate: possible induction of benign prostatic hyperplasia. 1110 9

44 patients seeked medical advice for low urinary symptoms. Their examination consisted of digital rectal investigation, test for prostate-specific antigen (PSA) in the serum, transurethral ultrasonic investigation, fine needle multifocal biopsy of the prostate. Three groups were identified by the PSA levels. 7 patients of group 1 had PSA up to 6 ng/ml. Cancer was diagnosed in 3 of them, prostatic intraepithelial neoplasia (PIN) in 4 patients. 16 patients of group 2 had PSA within 7-10 ng/ml. In this group only 1 patient had cancer, the rest 15 had PIN. 21 patients of group 3 with PSA at least 10 ng/ml had cancer, benign prostatic hyperplasia, PIN (12, 2 and 7 patients, respectively). 3 patients with high-grade PIN and PSA above 10 ng/ml in 6 months were diagnosed to have adenocarcinoma, in 6 such patients signs of dysplasia disappeared after antiandrogenic therapy. Further investigations on diagnosis and treatment of PIN are desirable.
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PMID:[Intraepithelial prostatic neoplasia]. 1114 38


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