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Query: UMLS:C0282612 (PIN)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to characterize the pathological features of hereditary prostate cancer, a recently recognized variant of prostate cancer with an autosomal dominant inheritance of a rare highly penetrant gene associated with early onset of disease. We compared the histology at radical prostatectomy of clinical stage T2 prostate cancer, including its relationship to prostatic intraepithelial neoplasia, in men with a family history of prostate cancer to those without a family history of prostate cancer. Three cohorts (hereditary, familial and sporadic) were identified based on pedigree analysis. A hereditary subgroup (28 patients) met 1 of the following 3 criteria: 1) cluster of greater than 3 affected relatives within the nuclear family, 2) occurrence of prostate cancer in each of 3 generations in either the proband paternal or maternal lineage, or 3) a cluster of 2 relatives affected at an early age of less than 55 years. This subgroup was compared to an age-matched subgroup with family history of prostate cancer (26 patients) yet the aforementioned conditions for inclusion within the hereditary subgroup were not met and to a sporadic subgroup without a family history of prostate cancer (27 patients). All parameters were statistically similar among the groups except that hereditary and familial group multifocal tumors were of lower grade (p = 0.0001), sporadic cases had a greater proportion of small multifocal cancers associated with prostatic intraepithelial neoplasia (p = 0.02) and the familial group had a weaker correlation between total tumor volume and grade. In conclusion, our analysis failed to demonstrate substantial pathological differences among hereditary, familial and sporadic forms of prostate cancer. Rather, our data are remarkable for the wide range of all parameters studied in each group. Even the sporadic cases had features, such as increased numbers of precursor lesions and tumor multifocality, which in other organs are commonly associated with either hereditary cancer or cancer arising in a field effect due to diffuse exposure to a carcinogen.
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PMID:Pathological features of hereditary prostate cancer. 785 89

Over a period of 25 weeks 434 needle biopsy specimens of the prostate were sent to the author for consultation because of diagnostic concerns. The final diagnoses were cancer (69%), benign (13%), atypical but not diagnostic (10%), high grade prostatic intraepithelial neoplasia (PIN) (5%), and miscellaneous (3%). The most common benign entities mimicking cancer were atrophy (29 specimens) and adenosis (19 specimens). The 300 cancer specimens were analyzed further. Architecturally, the presence of small glands between larger benign glands was the most common pattern seen in 80% of carcinomas; haphazard growth patterns, single cells, and cribriform glands were seen less frequently. The following diagnostic features were helpful: nuclear enlargement (77% of specimens); prominent nucleoli (76%); pink acellular intraluminal secretions (53%); amphophilic cytoplasm (39%); blue-tinged mucinous secretions (34%); crystalloids (25%); PIN (13%); mitotic figures (11%); and perineural invasion (3%). The mean and median numbers of malignant glands in this series were 31 and 20, respectively (range, two to 300). Tumors with a Gleason score lower than 6 caused greater diagnostic problems for referring physicians because these tumors had a greater number of malignant glands, yet were still sent in for consultation (P = .0018). Gleason score was positively correlated with prominent nucleoli and amphophilic cytoplasm and inversely correlated with the presence of crystalloids. Prominent nucleoli, which often are quoted as being essential for the diagnosis of prostate cancer, were not seen in 24% of the specimens and seen only rarely in another 25%. The diagnosis of prostate cancer is based on a constellation of features. Even in this series with a limited number of malignant glands, 85% of specimens contained three or more of the above-listed diagnostic features in addition to architectural atypia.
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PMID:Diagnostic criteria of limited adenocarcinoma of the prostate on needle biopsy. 786 53

Neuroendocrine cells are thought to have a regulatory role in prostatic epithelial growth and may be prognostically useful in prostatic adenocarcinoma. To determine the extent of neuroendocrine differentiation in high-grade prostatic intraepithelial neoplasia (PIN), a putative precursor of cancer, we studied the immunohistochemical expression of 10 markers in 26 radical prostatectomy specimens with PIN and adenocarcinoma. Expression was measured as mean percent of positive cases and positive high-power (x40) fields. The highest percentage of cases showed immunoreactivity for serotonin (73%, PIN; 54%, carcinoma), neuron-specific enolase (NSE) (67%, PIN; 46%, carcinoma), chromogranin (62%, PIN; 65%, carcinoma), and human chorionic gonadotropin (hCG) (30%, PIN; 22%, carcinoma); the remaining markers showed immunoreactivity in fewer than 5% of cases (somatostatin, calcitonin, corticotropin) or in no cases (thyrotropin, prolactin, and glucagon). At least one of the markers was present in 88% of cases of PIN and 92% of carcinoma. Non-neoplastic epithelial cells expressed serotonin, NSE, chromogranin, and hCG in every case, and the expression was significantly greater than in PIN and cancer. Stepwise regression analysis revealed the following positive correlations: chromogranin expression in PIN and patient age, NSE expression in cancer and number of lymph node metastases, and hCG expression in cancer and percentage of Gleason pattern 5; serotonin expression in PIN and cancer did not correlate with any of the clinical and pathologic factors. Neuroendocrine differentiation is downregulated in prostatic carcinogenesis, with intermediate levels of expression in PIN compared with normal cells and carcinoma.
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PMID:Neuroendocrine differentiation in prostatic intraepithelial neoplasia and adenocarcinoma. 797 47

Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 11, and 12 was used to evaluate multiple 18-gauge needle biopsy cores from 50 randomly selected radical prostatectomy specimens. FISH analysis detected 26 diploid (52%), 7 tetraploid (14%), and 17 aneuploid tumors (34%). The FISH results were concordant with flow cytometric (FCM) DNA content measurements of the corresponding prostatectomy specimens for 31 tumors. For the 19 FISH/FCM discordant tumors, FISH was more sensitive than FCM for detecting ploidy anomalies. Common numerical chromosome alterations were gains of chromosomes 7 and 8, which were found in 13 (76%) and 10 (59%) aneuploid tumors, respectively. Gain of chromosome 7 was strongly associated with higher Gleason score (> or = 8) (P < 0.0001) and with advanced tumor pathological stages (stages T3 + T4; P < 0.01). Gain of chromosome 8 also correlated with higher Gleason score (P < 0.01). FISH showed intratumoral ploidy heterogeneity in 3 of 41 (7%) studied tumors. Among 17 noncancerous adjacent tissue specimens, chromosome alterations were observed in one, which contained high-grade prostatic intraepithelial neoplasia. Combined FISH and fluorescent leukocyte common antigen staining showed that infiltrating leukocytes do not contribute to the observed gains of chromosomes 7 and 8 in prostate cancer tissue. These results demonstrate that (a) FISH analysis of prostate needle biopsy-sized specimens can be a practical, sensitive method for determination of nuclear ploidy and numerical chromosome alterations; and (b) gains of chromosomes 7 and 8 are common numerical alterations of prostate cancer cells and may be potential markers of tumor behavior and patient prognosis.
Cancer Res 1994 Jul 01
PMID:Potential markers of prostate cancer aggressiveness detected by fluorescence in situ hybridization in needle biopsies. 801 84

Cytogenetic and molecular biological studies have demonstrated deletion of sequences that map to the short arm of chromosome 8 (8p) in tumors from several organ systems, including sequences that map within or near 8p22 in human prostate tumors. Recent studies in our laboratory have suggested that deletion of sequences on 8p may be concurrent with alterations in dosage for chromosome 8. In order to further investigate this finding, the present study has applied fluorescence in situ hybridization (FISH) techniques to determine the status of chromosome 8 in prostate tumors that have undergone deletion of sequences at 8p22. Dosage of 8p22 sequences was assayed utilizing unique sequence cosmid DNA probes by FISH and confirmed by amplification of microsatellite sequences by polymerase chain reaction (PCR). Chromosome 8 dosage was assayed by FISH utilizing both unique sequence cosmid probe DNA (specific to the 8q13.1-q13.3 chromosomal region) and pericentromeric probe DNA. FISH analysis of 10 specimens of normal or benign prostatic hyperplasia tissues paired with 9 tumor and one prostatic intraepithelial neoplasia tissues from the same patients for dosage at 8p, 8cen, and 8q, and PCR analysis for dosage at 8p, demonstrated that (a) FISH provided a more precise means of evaluating allelic loss than PCR in prostate tissue; (b) 8p22 sequence losses occurred frequently in prostate tumors; (c) 8p22 sequence losses were most often detected in the absence of 8cen or 8q sequence dosage alterations, although they were sometimes accompanied by gain or loss of 8cen or 8q sequences; and (d) the pattern of 8p22 sequence losses was most often widespread rather than focal. This study is the first to describe FISH analysis of interphase nuclei within tissue sections using cosmid probe DNAs.
Cancer Res 1994 Jul 15
PMID:Fluorescence in situ hybridization analysis of 8p allelic loss and chromosome 8 instability in human prostate cancer. 803 2

The basic cancer-related chemical and biological sciences, pathology, and epidemiology have contributed to the understanding that antimutagenesis and antiproliferation are the important general mechanisms of chemoprevention and to the development of antimutagenic and anti-proliferative agents as potential chemopreventive drugs. These disciplines have also provided the biochemical and histopathological bases for identifying intermediate biomarkers that can be used as surrogate end points for cancer incidence in clinical chemoprevention trials and for selecting cohorts for these trials. Particularly important as histological biomarkers of cancer are the cytonuclear morphological and densitometric changes that define intraepithelial neoplasia (IEN). IEN changes are on the causal pathway to cancer. They may serve as target lesions in Phase II chemoprevention trials and as standards against which other earlier cellular and molecular biomarkers can be evaluated. Strategies for the clinical evaluation of chemopreventive agents have been defined for seven targets--colorectal, prostate, lung, breast, bladder, oral, and cervical cancers. Cohorts have been identified for short-term Phase II trials that investigate the effects of chemopreventive agents on IEN and on earlier biomarkers. Patients with adenomas serve as a cohort for trials in colon. One cohort for Phase II trials in prostate is patients with early stage cancers scheduled for prostatectomy; another is patients with prostatic intraepithelial neoplasia (without prostatic carcinoma). Patients treated for lung cancer are at high risk for bronchial dysplasia and second cancers; such patients are a cohort for Phase II trials in lung cancer. Presurgical breast cancer patients and patients with ductal or lobular carcinoma in situ are cohorts for studies in breast. Patients with superficial bladder cancers (Ta/T1 with or without carcinoma in situ) are cohorts for studies of chemoprevention in bladder, and patients with dysplastic oral leukoplakia are evaluated for chemoprevention of oral cancers. Cervical intraepithelial neoplasia is a prototype IEN, and patients with cervical intraepithelial neoplasia are a cohort for studies of cervical cancer.
Cancer Res 1994 Apr 01
PMID:Progress in cancer chemoprevention: perspectives on agent selection and short-term clinical intervention trials. 813 31

It has been suggested that poorly differentiated areas in prostatic carcinoma evolve from more well differentiated cancer with time and increasing tumor volume. However, the association of high grade tumor with increasing tumor volume may merely reflect a growth advantage of the high grade tumor, whereby most high grade tumors would be large by the time they were clinically detected. Prior reports analyzing the relationship of tumor volume and grade suffer from studying fairly advanced tumors in which the relationship of tumor volume and grade at inception of prostate cancer could not be addressed. We evaluated 720 individual tumor foci in 153 radical prostatectomy specimens removed for early prostate cancer detected by screening techniques. Although tumor volume was related to grade, the correlation was weak (r = 0.254). Of 13 peripherally located high grade tumors (Gleason score 8 to 10) 6 (46%) were less than 1 cc. Of 106 peripheral tumors with some Gleason pattern 4 or 5 component 48 (45%) were less than 1 cc. These small high grade tumors were frequently associated with high grade prostatic intraepithelial neoplasia. Small high grade cancers were uncommon within the transition zone, where there exists a greater tendency for large low grade cancers to arise. In this radical prostatectomy series of nonpalpable prostate cancer 9% of the prostates contained tumor foci that were predominantly Gleason pattern 4 or 5 and that measured 1 cc or less. Based on these findings, if some patients with low to intermediate grade cancer are to be followed expectantly, they should undergo widespread sampling of the prostate to enhance the detection of multifocal small high grade disease. The finding of a large proportion of low volume, high grade carcinoma reveals that prostate cancer has the potential to be high grade early in its course and need not arise from low grade carcinoma that has evolved with time and volume.
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PMID:Small high grade adenocarcinoma of the prostate in radical prostatectomy specimens performed for nonpalpable disease: pathogenetic and clinical implications. 818 70

The incidence of clinically detected prostate cancer is increasing with more frequent diagnosis in younger male patients. Whether this represents a genuine increase in incidence or earlier detection is not clear. To understand better the evolution and early changes of prostate cancer we evaluated 152 prostate glands from young male patients 10 to 49 years old. Of the prostates 98 were from African-Americans and 54 were from white patients. Prostatic intraepithelial neoplasia was identified in 0%, 9%, 20 and 44%, and small foci of histological cancer in 0%, 0%, 27% and 34% of the male patients in the second, third, fourth and fifth decades of age, respectively. The majority of the cases of prostatic intraepithelial neoplasia were of low grade. High grade prostatic intraepithelial neoplasia, found in 5 prostates, was first identified in the fifth decade. All 5 cases occurred in prostates containing histological carcinoma. Incidental carcinoma was detected with a similar frequency in white and black patients. The cancerous foci were of similar size with a tendency for cancer in black patients to be multifocal, particularly in those in the fifth decade. We conclude that prostatic intraepithelial neoplasia and histological cancers are surprisingly common in young male patients of both races. The evolution of prostatic intraepithelial neoplasia and focal histological cancers is not clear but it appears to present several decades earlier than clinically detected carcinoma. The natural history of prostate cancer must encompass many more years (decades) than has been previously realized. In addition, the initiating events leading to clinically relevant prostate cancers likely occur at a remarkably young age.
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PMID:The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. 768 85

Cytogenetic studies were performed on 36 biopsies obtained from 26 primary prostatic adenocarcinomas. Following histopathological characterization of control sections, the biopsies were investigated using metaphase cytogenetics, DNA flow cytometry, and fluorescence in situ DNA hybridization. In 12 specimens, no carcinoma was found in control sections by histopathological means. In 24 carcinoma biopsies clonal aberrations were detected in 15 specimens. Tetraploidy as sole aberration was detected in five specimens. Loss of the Y chromosome was seen in eight samples. Only one tumor revealed structural abnormalities. Eight samples were found to be normal (46,XY). Remarkably, nonclonal chromosome aberrations, particularly marked chromosome loss, were frequently detected in prostatic carcinomas and premalignant lesions (prostatic intraepithelial neoplasia). In the series of biopsies investigated by means of cytogenetics and flow cytometry, biopsies with aneuploid DNA content were found to be cytogenetically normal. Conversely, the cytogenetically aberrant clones were found to be of diploid DNA content. Evidence of focal intratumoral heterogeneity was revealed by cytogenetics, flow cytometry, and in situ hybridization.
Cancer Res 1993 Sep 01
PMID:Genotypic characterization of prostatic carcinomas: a combined cytogenetic, flow cytometry, and in situ DNA hybridization study. 835 32

A comparative study of primary prostatic tumors utilizing conventional metaphase analysis of prostate tumor cultures and fluorescence in situ hybridization (FISH) analysis of paraffin-embedded tissue sections revealed significant differences in type and extent of cytogenetic aberrations. Clonal trisomy 7 was identified in two tumors by metaphase analysis of prostate cultures, but not confirmed in either case by FISH analysis. True gain of chromosome 8 was revealed by FISH analysis in malignant epithelium of four tumors but not in adjacent normal or hyperplastic glands. Neither gain nor loss of this chromosome was observed by metaphase analysis in any of the tumors. Significant monosomy and nullisomy of chromosome 10 was identified in one case by FISH, but no cells with gain or loss of chromosome 10 were observed by metaphase analysis. Significant loss of the Y chromosome was revealed in one tumor by FISH, but no cells with -Y were identified by metaphase analysis. Clonal loss of the Y chromosome was identified in two other tumors by metaphase analysis. Paraffin FISH analysis of these tumors revealed overall monosomy in both, although in one tumor there was extensive nodular loss of the Y chromosome. Paraffin FISH analysis permits identification of cytogenetic aberrations in areas identified as carcinoma (CaP), prostatic intraepithelial neoplasia (PIN), and benign prostatic hyperplasia (BPH). This technique appears more informative in defining the true extent and nature of cytogenetic aberrations in prostate cancer than metaphase analysis of prostate tumor cultures.
Cancer Genet Cytogenet 1993 Aug
PMID:Defining the extent and nature of cytogenetic events in prostatic adenocarcinoma: paraffin FISH vs. metaphase analysis. 837 4


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