Biomedical subjects

R B Jenkins

Publications and source records attributed to R B Jenkins.

At least 73 records · Page 4Linked to original sources

PubMed1997

Clinical correlations of immunophenotypic variations and the presence of trisomy 12 in B-cell chronic lymphocytic leukemia.

In a prospective study of 93 consecutive untreated patients with B-cell chronic lymphocytic leukemia, we examined the clinical relevance of surface immunoglobulin (sIg) heavy chain (HC) and light chain (LC) isotypes, CD11c or CD25 expression, and the presence of trisomy 12 by fluorescence in situ hybridization (FISH). Careful morphologic evaluation was performed to exclude patients with other forms of chronic lymphoid leukemias, including mantle cell lymphoma, prolymphocytic leukemia, and leukemia phase of lymphoma. In addition, clonally restricted sIg and CD5 surface determinant were expressed in all patients. Clinical presentation, including blood cell counts, clinical stage, and organomegaly, did not correlate with any of the measured variables. After a median follow-up period of 3 years, the particular HC or LC isotype or CD11c expression did not correlate with either disease progression or treatment-free survival. However, trisomy 12 and CD25 expressions were both associated with accelerated disease progression and a shorter treatment-free survival time. Our results confirm the adverse prognostic significance of trisomy 12 expression in chronic lymphocytic leukemia and suggest that CD25 expression may have an unfavorable clinical impact.

Adult↗

PubMed1997

Soft-tissue perineurioma. Evidence for an abnormality of chromosome 22, criteria for diagnosis, and review of the literature.

Reported herein are two examples of soft-tissue perineurioma (STP), one arising in the maxillary sinus and the other in subcutaneous tissue of the thigh. Electron microscopy and immunohistochemistry were performed in both cases. Based on our findings and a critical review of the literature, STPs are generally small, well-circumscribed but not encapsulated tumors. Histologically, most STPs resemble fibroblastic tumors, being composed of elongated, wavy cells. The immunohistochemical reactivity for epithelial membrane antigen, the lack of reactivity for S-100 protein, and the presence of ultrastructural features of perineurial cells are typical of this tumor. To explore the possibility that STP, like the intraneural variety of perineurioma, exhibits an abnormality of chromosome 22, we performed fluorescence in situ hybridization with a probe specific for the M-bcr locus, which maps to the chromosome band 22q11. In both our tumors, a high percentage of nuclei having only one M-bcr signal (44 and 96%) was observed. Our findings indicated deletion of part or all of chromosome 22 and support the view that both soft-tissue and intraneural perineurioma are part of a spectrum of perineurial neoplasia.

Chromosome Aberrations↗

PubMed1997

Detection of p16 gene deletions in gliomas: a comparison of fluorescence in situ hybridization (FISH) versus quantitative PCR.

The p16 protein plays a key role in cell cycle control by preventing CDK4 from inactivating the retinoblastoma protein (pRb). The corresponding tumor suppressor gene (p16/MTS1/CDKN2) has recently been implicated in malignant progression of astrocytomas and could potentially serve as an important marker for patient prognosis and for guiding specific therapeutic strategies. We have undertaken a study to evaluate 2 methods of detecting p16 deletion. Thirty diffuse gliomas were analyzed for p16 gene dosage. Dual color fluorescence in situ hybridization (FISH) was performed on cytologic preparations using paired centromeric (CEN) and locus-specific probes for CEN9/p16, CEN8/RB, and CEN12/CDK4. Quantitative PCR was performed using primers for p16, MTAP, and reference genes. Eleven cases were also studied using comparative genomic hybridization (CGH). Abnormalities of the p16-CDK4-RB pathway were identified in 21 (70%) cases by FISH and/or PCR. These included 15 (50%) with p16 deletion, 9 of which were detected by both techniques, 3 by FISH alone, and 3 by PCR alone (concordance rate = 81%). FISH analysis further revealed tetraploidy/aneuploidy in 14 (47%), RB deletion in 11 (37%) and CDK4 amplification in 1 (3.3%). There were 94% and 100% concordance rates between CGH and FISH or PCR, respectively. Quantitative PCR was noninformative in 4 cases. Although FISH and quantitative PCR are both reliable techniques, each has limitations. PCR is likely to miss p16 deletions when there is significant normal cell contamination or clonal heterogeneity, whereas the p16 YAC probe used for FISH analysis may miss small deletions. Replacement of the latter with a cosmid probe may improve the sensitivity of FISH in future experiments.

Brain Neoplasms↗

PubMed1997

Frequent loss of heterozygosity on chromosomes 3p and 17p without VHL or p53 mutations suggests involvement of unidentified tumor suppressor genes in follicular thyroid carcinoma.

Follicular thyroid carcinoma (FTC) exhibits frequent loss of heterozygosity (LOH) on chromosomes 10q and 3p, suggesting involvement of tumor suppressor genes. We screened 14 FTC (10 Hurthle cell carcinomas and 4 nonoxyphilic FTC), 14 papillary thyroid carcinomas, and 7 follicular adenomas for LOH on chromosome arms 1p, 3p, 3q, 10p, 10q, 11p, 11q, 13q, 17p, and 17q. LOH was more frequent in FTC than in follicular adenoma or papillary thyroid carcinoma. In FTC, rates of LOH on 3p (86%), 17p (72%), and 10q (57%) were higher than the average rate of LOH (33%; P < 0.05). Most frequently involved were 3p21-25 and 17p13.1-13.3, the sites for the VHL (3p25-26) and p53 (17p13.1) tumor suppressors. We, therefore, characterized these genes by dideoxy fingerprinting and DNA sequencing. Two FTC had mutations in p53, but only 1 of these exhibited LOH at 17p. No VHL gene mutations were found. Thus, neither p53 nor VHL genes play a significant role in the pathogenesis of differentiated thyroid cancer. LOH on 17p, but not on 3p or 10q, was correlated with mortality. Accordingly, 3p and 10q LOH may represent early, and 17p LOH late, events in FTC development. The data suggest the presence of novel tumor suppressor genes on chromosomes 3p and 17p that may be important in the pathogenesis of FTC.

Adenocarcinoma, Follicular↗

PubMed1997

Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value.

Consecutive paraffin sections of 105 astrocytomas and 15 oligoastrocytomas were examined for expression of p53, MIB-1 (Ki-67), and proliferating cell nuclear antigen (PCNA). The tumors had been examined previously for genetic abnormalities and by flow cytometry. Regardless of the tumor's stage and grade and the patient's age and gender, p53 expression was found in 40% of tumors. Although p53 expression was associated with a loss on chromosome 17p and was more frequent in aneuploid tumors, it had no association with survival time. The MIB-1 and PCNA labeling indices increased with increasing tumor grade but showed no association with other clinicopathological parameters. In individual tumors, there was poor concordance between any of the variables (MIB-1, PCNA, and p53). Results for p53 and MIB-1 were similar for both astrocytomas and oligoastrocytomas. The MIB-1 and PCNA values appeared to have prognostic utility in univariate analysis but not after adjusting for patient age and tumor grade. The poor concordance between MIB-1 and PCNA in individual tumors indicates that any one means of assessing proliferative potential in gliomas may not be reliable.

Adolescent↗

PubMed1997

Chromosomal anomalies in stage D1 prostate adenocarcinoma primary tumors and lymph node metastases detected by fluorescence in situ hybridization.

PURPOSE: We determined if characteristic chromosomal anomalies exist within the primary tumors and lymph node metastases in patients with stage D1 prostate cancer, and compared the patterns of chromosomal alterations between primary tumors and nodal metastases. MATERIALS AND METHODS: Fluorescence in situ hybridization analysis using peri-centromeric probes for chromosomes 6, 7, 8, 17, X and Y was performed on 5 mu. sections from paraffin embedded tissue blocks obtained from 23 consecutive patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy in 1990 for stage D1 prostate cancer. RESULTS: The dominant focus of primary tumor was compared to matched nodal metastases in 12 cases. Five of 12 primary tumor foci (41.7%) had similar chromosomal gains and the same fluorescence in situ hybridization ploidy result as the corresponding nodal metastases. Chromosomes 7 and X (73.2% of cases) were most frequently gained in the primary tumors, and chromosomes X and Y (81.2% of cases) were most frequently gained in the metastases. No primary tumor or metastasis demonstrated chromosomal loss. Three of 19 primary tumors (15.7%) were diploid, while 16 of 19 (84.3%) were nondiploid. Chromosomal aneusomy was inversely correlated with increasing Gleason summary score. CONCLUSIONS: These data indicate that the dominant primary tumor foci may not give rise to nodal metastases, gains of chromosomes 7, X and Y may be associated with metastatic behavior, and patients with stage D1 disease have a greater rate of aneuploidy than those with lower stage cancer.

Adenocarcinoma↗

PubMed1997

Simultaneous chromosome 7 and 17 gain and sex chromosome loss provide evidence that renal metanephric adenoma is related to papillary renal cell carcinoma.

PURPOSE: Metanephric adenoma has recently been recognized as a unique renal tumor characterized by an unusual degree of cellular differentiation and maturation. We recently studied metanephric adenoma using metaphase analysis and observed concomitant chromosome Y loss and chromosome 7 and 17 gain. To determine if these chromosomal anomalies are consistently present in renal metanephric adenoma, we studied all 11 tumors in the pathology tissue registry at our institution using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: FISH, using deoxyribonucleic acid probes for chromosomes 1, 7, 8, 17, X and Y, was performed in isolated nuclei from 11 paraffin embedded renal metanephric adenoma specimens. RESULTS: Of the 11 tumors (73%) 8 demonstrated chromosome 7 and 17 gain by FISH, and the remaining 3 were found to have an apparently normal chromosomal content. Of the 8 tumors (75%) from men showed 6 chromosome 7 and 17 gain with Y chromosome loss. Of the 3 tumors (33%) from women 1 had chromosome 7 and 17 gain with X chromosome loss, while 1 had chromosome 7 and 17 gain without sex chromosome aneusomy. Metaphase analysis performed on 2 tumors revealed chromosome 7 and 17 gain and Y chromosome loss in 1, and no apparent, chromosome anomaly in the other, confirming the results of FISH analysis. CONCLUSIONS: FISH analysis of renal metanephric adenoma identified frequent chromosome 7 and 17 gain and sex chromosome loss. These results are consistent with a clonal neoplastic disorder in which chromosomes 7, 17, X and Y are likely to be involved in the pathogenesis of this tumor. These characteristic chromosomal alterations have also been observed in papillary renal cell adenoma and papillary renal cell carcinoma, providing evidence that these tumors may be related.

Adenoma↗

PubMed1997

Detection of chromosomal anomalies and c-myc gene amplification in the cribriform pattern of prostatic intraepithelial neoplasia and carcinoma by fluorescence in situ hybridization.

Grading of the cribriform pattern of prostate cancer is controversial, and the genetic changes are largely unknown. Furthermore, the pathogenetic relationship between the cribriform pattern of high-grade prostatic intraepithelial neoplasia (PIN) and cribriform carcinoma is poorly understood. We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y and a region-specific probe for c-myc to evaluate genetic changes in matched foci of high-grade PIN (48 foci) and prostatic carcinoma (71 foci) in 25 whole-mount radical prostatectomy specimens from patients with metastatic cancer. These cases included 10 foci of cribriform PIN and 10 foci of cribriform cancer. Numeric chromosomal anomalies were found in 67 and 68% of the high-grade PIN and carcinoma foci, respectively. Extra copies of the c-myc gene were identified in 52 and 44% of the high-grade PIN and carcinoma foci, respectively. The cribriform pattern of cancer had a higher percentage of foci with gain of chromosomes 7, 12, and Y, loss of chromosome 8, and extra copies of c-myc gene than other Gleason Primary Patterns 3 and 4; there was no difference, however, for all paired comparisons of genetic changes between the cribriform pattern of cancer and Gleason Primary Pattern 5 cancer. Cribriform PIN and cribriform cancer generally exhibited similar anomalies, although the percentage of foci with gain of chromosomes 10 and 12 was higher in cribriform cancer. Our results indicate that the cribriform pattern of prostate cancer shares genetic changes with Gleason Primary Pattern 5 and that both contain more genetic changes than the cribriform pattern of PIN. These findings suggest that the cribriform pattern of prostate cancer has biologic similarity with Gleason Pattern 5 carcinoma and that the cribriform pattern of PIN is closely associated with the cribriform pattern of prostatic carcinoma.

Adenocarcinoma↗

PubMed1997

Lack of germ-line mutations of CDK4, p16(INK4A), and p15(INK4B) in families with glioma.

Gliomas are tumors of the central nervous system that may be inherited in some patients. The gene(s) responsible for the clustering of gliomas in families have not yet been identified. Molecular studies of sporadic high-grade gliomas have revealed mutations or deletions of the genes encoding the protein kinase inhibitors p16(INK4A) and p15(INK4B) in a large proportion of tumors. Moreover, those tumors without deletions frequently display gene amplification and/or over-expression of mRNA encoding the protein kinase cdk4. We hypothesized that germ-line mutations in the p16(INK4A), p15(INK4B), or CDK4 genes might contribute to some cases of familial gliomas. To address this issue, we analyzed 36 kindreds with a predisposition to glial tumors. Genomic DNA from index members of these families was screened by PCR-single-strand conformational polymorphism analysis. We did not detect any functional mutations in the p16(INK4A), p15(INK4B), or CDK4 genes, although two individuals did have a previously described A140T polymorphism in p16(INK4A). Thus, despite the association between the sporadic forms of high-grade glioma and abnormalities of p16(INK4A), p15(INK4B), or CDK4, we found no evidence that germ-line mutations in the coding region of these three genes predispose to inherited glial tumors.

Adult↗

PubMed1996

Application of fluorescent in situ hybridization with X and Y chromosome specific probes to buccal smear analysis.

Conventional X- and Y-chromatin and fluorescent in situ hybridization (FISH) analysis based on X- and Y-chromosome specific probes were conducted from buccal smear, on 15 normal males, 15 normal females, and 9 cases suspected of sex chromosome anomalies. The proportion of X- and Y-chromatin in normal females and males was 12% +/- 3% and 51.5% +/- 4.9%, respectively, by the conventional X- and Y-chromatin procedure. The CEP-X/Y analysis by FISH for the same specimens provided a proportion of 98.8% +/- 0.7% cells with XX signals in the normal females and 99.8% +/- 0.4% cells with XY signals in the normal males. The FISH method was superior to the conventional procedure in nine cases suspected of sex chromosome anomalies, including one case of mosaicism. The results of CEP-X/Y will sometimes be false; it will not detect structural anomalies of sex chromosomes, and it is not intended to detect low level mosaicism. However, the test is useful for rapid screening of sex chromosome aneuploidy at a fraction of the cost for chromosome analysis. The FISH test is also appropriate to detect tissue specific sex chromosome mosaicism, especially if it is relatively high. This FISH test is best used as an adjunct to chromosome analysis whenever possible.

Adolescent↗

PubMed1996

Allelic imbalance and microsatellite instability in prostatic adenocarcinoma.

Although prostate cancer is one of the most common malignancies of males in Western countries, relatively little is known about the molecular mechanisms involved in tumor initiation and progression. Allelic loss studies have suggested the involvement of multiple tumor suppressor genes (TSGs), but few detailed studies of all chromosomes have been performed. In an effort to localize and identify candidate TSGs, we performed allelic imbalance (AI) studies on 55 prostate cancers, using 135 polymorphic microsatellite markers. For the entire chromosome. AI ranged from a low of 0% on chromosomes 14 and 20 to a high of 71% on chromosome 8. Chromosomal regions demonstrating at least twice the background frequency of AI (ranging from 20 to 69%) included 5q, 6q, 7q, 8p, 13, l6q, l8q, and 21. In addition, AI was examined for association with a number of clinicopathological parameters. AI on chromosomes 7 and 16 were each associated with greater age at diagnosis (P = 0.009 and 0.001, respectively), and AI on chromosomes 10, 16, and 18 was associated with aneuploidy/tetraploidy (P = 0.037, 0.013, and 0.054, respectively). Furthermore, AI on chromosome 5 was associated with a higher pathological stage (P = 0.021) and on chromosome 8 and 16 with a higher Gleason score (P = 0.027 and 0.041, respectively). No tumor exhibited a phenotype of widespread microsatellite instability. These results indicate that there likely exist multiple sites harboring candidate TSG in prostate cancer, some of which may have important clinical implications, and which argue against widespread microsatellite instability.

Adenocarcinoma↗

PubMed1996

Cytogenetic analysis of aggressive meningiomas: possible diagnostic and prognostic implications.

BACKGROUND: Published karyotypes from aggressive (atypical and malignant) meningiomas are few, but suggest clonal evolution from benign tumors with monosomy 22 to aggressive forms with additional abnormalities. The goal of this study was to identify the most frequent karyotypic abnormalities associated with aggressive histopathology and biologic behavior. METHODS: Eight intracranial meningiomas exhibiting histologically atypical features at the time of intraoperative diagnosis were chosen for cytogenetic analysis. The study set was comprised entirely of histologically atypical meningiomas. Four were considered malignant; three on the basis of brain invasion and one due to extracranial metastases. None was histologically anaplastic. RESULTS: Chromosomal abnormalities were demonstrated in 6 cases (75%), 5 of which were complex (63%). Loss of chromosome 22 was identified in two cases, both of which were associated with additional aberrations. Abnormalities most frequently involved chromosomes 1 (63%), 3 (50%), and 6 (63%). Four cases (50%) had dicentric or ring chromosomes. An additional 47 previously reported karyotypes from atypical and malignant meningiomas were reviewed. Comparison with published karyotypes of 200 histologically benign meningiomas served to underscore the increased frequency of complex karyotypes, chromosome 1, 3, and 6 abnormalities, and telomeric associations in the aggressive tumors. Apparently normal karyotypes as well as monosomy 22 alone were more frequently associated with benign, nonatypical histopathology. CONCLUSIONS: These findings suggest a possible role for cytogenetic analysis in determining the prognosis and perhaps in refining the diagnosis of atypical or aggressive meningiomas. Further studies are necessary to determine the significance of complex karyotypes, chromosome 1, 3, and 6 abnormalities, and telomeric associations, particularly whether they portend a more aggressive clinical course in meningiomas lacking features of histologic atypia.

Adult↗

PubMed1996

The glial and mesenchymal elements of gliosarcomas share similar genetic alterations.

The cellular origin of the sarcomatous component of gliosarcomas is controversial. It is not clear if the sarcoma arises in transition from the glial cells that comprise the gliomatous component or independently arises from non-neoplastic mesenchymal cells of the tumor stroma. Using comparative genomic hybridization (CGH) along with cytogenetic analysis, fluorescence in situ hybridization (FISH) analysis, and polymerase chain reaction (PCR) analysis of microsatellite allelic imbalance, we have evaluated the genetic alterations in the gliomatous and sarcomatous components of five gliosarcomas. The glial element was grade 4 fibrillary astrocytoma (glioblastoma multiforme) in all five tumors. The sarcoma elements were fibroblastic without osseous, chondroid, or angiosarcomatous differentiation. Gain of chromosome 7, loss of chromosome 10, deletions of the chromosome 9 p-arm, and alterations of chromosome 3 were frequently observed, demonstrating that gliosarcomas can be genetically classified as belonging to the spectrum of glioblastomas. Furthermore, the sarcomatous and gliomatous portions of each gliosarcoma investigated were similar with respect to both the presence and absence of specific genetic alterations. This observation supports the hypothesis that the sarcomatous component of a gliosarcoma either arises from the same common precursor cell as the gliomatous portion, or it arises from the gliomatous portion itself.

Adult↗

PubMed1996

Potential markers of aggressiveness in prostatic intraepithelial neoplasia detected by fluorescence in situ hybridization.

OBJECTIVE: High-grade prostatic intraepithelial neoplasia (PIN) represents the most likely precursor of prostatic adenocarcinoma. In this review, we discuss the utility of different techniques of interphase fluorescence in situ hybridization (FISH) in evaluating the genetic association between PIN and adenocarcinoma. METHODS AND RESULTS: Although the proportion of PIN and prostatic carcinoma foci that have chromosomal anomalies is similar, foci of carcinoma often have more alterations. This supports the hypothesis that PIN is a precursor of carcinoma. In some prostates, however, PIN foci have more alterations than matched carcinoma foci, suggesting that PIN foci can sometimes undergo more extensive chromosome evolution than carcinoma foci. Gain of chromosome 8 is the most common numerical alteration in prostatic carcinoma and PIN foci, and is associated with increasing cancer stage and grade. Thus, genes on chromosome 8 may play a role in the initiation and progression of prostatic carcinoma. One primary tumor focus usually shares chromosomal anomalies with associated lymph node metastases, implying that only one primary lesion acquires genetic alterations that allow it to escape the prostate. CONCLUSIONS: PIN and prostatic carcinoma have similar genetic changes. This supports the hypothesis that PIN is often a precursor of carcinoma. Genes on chromosome 8 may play a role in both initiation and progression of prostatic carcinoma.

Adenocarcinoma↗

PubMed1996

Cytogenetic and microsatellite alterations in tumors from patients with the syndrome of myxomas, spotty skin pigmentation, and endocrine overactivity (Carney complex).

Carney complex (CC) is a familial multiple neoplasia and lentiginosis syndrome, transmitted in an autosomal dominant manner. It is the only familial form of cardiac and skin myxomas known and includes endocrine neoplasms causing Cushing's syndrome [primary pigmented nodular adrenocortical disease (PPNAD)] and acromegaly (GH-producing adenoma). The molecular defect leading to CC remains unknown, but was recently mapped to chromosome 2p16 by linkage analysis. This region has exhibited cytogenetic aberrations in atrial myxomas from patients with CC and harbors the hMSH2 and hMSH6 genes, which are involved in the preservation of microsatellite length stability of replicating human cells. In the present study, we examined 15 tumor and normal tissue specimens from 13 patients with CC [GH-producing adenoma (n = 1), adrenal tumors (PPNAD, n = 8), thyroid cancer (n = 1), normal adrenal gland (n = 1)] and 4 cultured cell lines [heart myxoma (n = 3) and eyelid myxoma (n = 1)]. Chromosome analysis was obtained by standard cytogenetic techniques. One of the myxoma cell lines and 3 PPNAD specimens contained multiple telomeric associations (tas). The normal adrenocortical tissue from a patient with PPNAD contained no apparent chromosomal anomalies, whereas the neighboring PPNAD tissue demonstrated tas. DNA was extracted from peripheral blood, tumor cell lines, and frozen or paraffin-embedded tissues and subjected to PCR amplification with primers from 64 microsatellite locations covering chromosomes 1 and 3-22 and 14 loci covering chromosome 2. The alterations detected were loss and gain of heterozygosity (LOH and GOH; 49% and 26%, respectively), deletions of both alleles (DEL; 10%), and microsatellite length instability (15%). GOH and LOH were the most frequent changes, with telomeric markers significantly over-represented (P < 0.05). Chromosomes 6, 11, 22, 10, and 19 demonstrated mostly LOH, GOH, or DEL in over 40% of the informative loci tested (73%, 59%, 47%, 46%, and 44%, respectively), whereas markers on chromosome 2 showed only microsatellite length instability (10%). The degree of genomic instability and its type were independent of tumor type (P > 0.1). We conclude that tumors and tumor cell lines from patients with CC demonstrate significant genomic, but not microsatellite length, instability. Thus, the CC gene(s) on chromosome 2p16 is different from the hMSH2 and hMSH6 genes and has dominant, rather than recessive, tumorigenic function. This gene(s) appears to be involved in the regulation of genomic stability of dividing cells, in particular the structure of telomeres in replicating chromosomes and/or the function of the mitotic apparatus.

Acromegaly↗

PubMed1996

Fluorescence in situ hybridization analysis of renal oncocytoma reveals frequent loss of chromosomes Y and 1.

PURPOSE: Cytogenetic studies of a small number of renal oncocytomas have indicated that loss of chromosomes 1 and Y may be involved in the pathogenesis of this tumor. To evaluate these observations further we selected paraffin embedded renal oncocytoma specimens from 20 male and 10 female patients for fluorescence in situ hybridization analysis. MATERIALS AND METHODS: Isolated nuclei were prepared from paraffin embedded specimens, and fluorescence in situ hybridization was performed with enumeration probes for chromosomes 1, 12, X and Y. RESULTS: Tumors from 10 male (50%) and 4 female (40%) patients demonstrated chromosomal alterations. Loss of chromosome Y was observed in specimens from all 10 male patients, and loss of chromosome 1 or gain of chromosome 12 was noted in 5 and 2 of these specimens, respectively. Of the 4 female patients with chromosomal abnormalities 2 had loss of chromosome 1, 1 had gain of chromosome 1 and 1 had gain of chromosome 12. CONCLUSIONS: Our results confirm that loss of chromosomes Y and 1 is common in renal oncocytoma, and that the alterations are probably involved in the pathogenesis of this tumor.

Adenoma, Oxyphilic↗

PubMed1996

Comparison of fluorescence in situ hybridization analysis of isolated nuclei and routine histological sections from paraffin-embedded prostatic adenocarcinoma specimens.

Fluorescence in situ hybridization (FISH) is a powerful tool for quantitative analysis of chromosomes and genes and can be applied in a variety of specimens, including cell cultures, isolated nuclei from fresh and fixed tissues, and histological tissue sections. However, the results of FISH analysis of isolated nuclei in prostate cancer have not been previously compared with those from histological sections from the paraffin-embedded tissue blocks. To compare these methods, we studied isolated nuclei derived from 50-microns sections and adjacent 5-microns tissue sections from 10 cases of benign nodular hyperplasia of the prostate and 16 cases of prostatic carcinoma. FISH analysis employed centromere-specific probes for chromosomes 7, 8, 11, and 12. In benign tissue, the percentage of nuclei with three or more signals for chromosomes 7, 8, 11, and 12 was less than 3% for both isolated nuclei and tissue sections. However, the percentage of nuclei with no and one signals was less than 8% for isolated nuclei and more than 24% for tissue sections. In prostatic carcinoma, numeric chromosomal anomalies were found in 75% of cases by both FISH methods. However, isolated nuclei had more chromosomal tetrasomy than tissue sections (mean, 9.2 to 11.0% versus 5.1 to 5.6%, respectively). Conversely, intratumor heterogeneity of chromosomal anomalies was identified in 5 cases by FISH analysis of tissue sections but not in isolated nuclei. Cancer ploidy analysis by FISH correlated well with ploidy analysis by flow cytometry, although FISH was more sensitive for aneuploidy. We conclude that FISH analysis of isolated nuclei and histological tissue sections from paraffin blocks are reliable methods for detection of chromosomal anomalies in archival tissue of prostate cancer, although each method has advantages and disadvantages.

Adenocarcinoma↗

PubMed1996

Aneusomies of chromosomes 8 and Y detected by fluorescence in situ hybridization are prognostic markers for pathological stage C (pt3N0M0) prostate carcinoma.

In an attempt to identify new prognostic markers, we performed fluorescence in situ hybridization (FISH) ploidy analysis of tumor tissue from patients with a targeted stage and histological grade of prostate carcinoma. We identified all 227 patients from the Mayo Clinic radical prostatectomy data base who had a high histological grade pathological stage C (pT3N0M0) tumor removed between 1966 and 1987. After histological review of the paraffin-embedded specimen blocks, 181 cases were suitable for FISH analysis using chromosome enumeration probes for chromosomes 7, 8, 10, 12, X, and Y. FISH detected 80 (44%) diploid, 22 (12%) tetraploid, and 79 (44%) aneuploid tumors. The common aneusomies were of chromosomes 7 and 8, which were present in 51 (28%) and 46 (25%) tumors, respectively. Aneusomies of chromosomes 10, 12, X, and Y were observed in 11 (6%), 15 (8%) 12 (7%) and 16 (9%) tumors, respectively. FISH aneuploid tumors showed a trend of more frequent systemic prostate cancer progression than nonaneuploid tumors (P = 0.060). For individual chromosome anomalies, gains of chromosome 8, aneusomy of chromosome 8, and aneusomy of chromosome Y correlated highly with systemic cancer progression (P = 0.006, 0.013, and 0.021, respectively). Gains of chromosome Y and aneusomy of chromosome Y were associated with an increased prostate cancer death rate (P < 0.001 for both). Multivariate analysis showed that gains of chromosome 8 and aneusomy of chromosome Y were significant independent "predictors" of systemic cancer progression (P = 0.008) and cancer death (P < 0.001), respectively. These results demonstrate that aneuploidy and specific aneusomies detected by FISH are potential markers for a poor prognosis in histological high-grade pathological stage C (pT3N0M0) prostate carcinoma.

Aged↗