Chromosomal changes in prostate cancer: A fluorescence in situ hybridization study

Das, Kakoli; Lau, W.S.; Sivaswaren, Christina Rudduck; Tan, Patrick; Fook‐Chong, Stephanie; Tien, Sim Leng; Cheng, C.

doi:10.1111/j.1399-0004.2005.00452.x

Cited by 24 publications

(25 citation statements)

References 25 publications

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“…The frequency of 8p deletions and 8q gains found in this study is substantially lower than in the majority of previous FISH studies, in which frequencies between 50.0% (5, 9) and 74% had been reported for 8p deletions (5,6,8,12,14,(27)(28)(29), and between 6.1% (30) and 73.3% (13) for 8q gains (5,7,9,12,29,30). This seeming discrepancy is mainly caused by the different aims and approaches of the different studies.…”

Section: Discussioncontrasting

confidence: 52%

“…Accordingly, thresholds were usually based on scores obtained in normal tissue. A deviation of +/− 2 or 3 SDs from the findings in normal tissues was used to define 8p/8q alterations by other authors (9,14,31). Under such criteria, cancers with a significant chromosomal instability leading to a certain number of nonclonal chromosomal alterations, including 8q+ or 8p−, will be identified as aberrant.…”

Section: Discussionmentioning

confidence: 99%

“…Deletions of 8p and gains of 8q are among the most frequent genomic alterations in prostate cancer. Several studies have proposed a relationship between 8p−/8q+ with adverse histopathologic findings (5)(6)(7)(8)(9)(10)(11). Studies suggesting associations with prostatespecific antigen progression, however, were limited to <100 cancers (12)(13)(14).…”

mentioning

confidence: 99%

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Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

Gammal¹,

Brüchmann²,

Zustin³

et al. 2010

Clinical Cancer Research

125

107

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Purpose: Deletions of 8p and gains of 8q belong to the most frequent cytogenetic alterations in prostate cancer. The target genes of these alterations and their biological significance are unknown.Experimental Design: To determine the relationship between chromosome 8 changes, and prostate cancer phenotype and prognosis, a set of 1.954 fully annotated prostate cancers were analyzed in a tissue microarray format by fluorescence in situ hybridization.Results: Both 8p deletions and 8q gains increased in number during different stages of prostate cancer progression. 8p deletions/8q gains were found in 26.1%/4.8% of 1,239 pT 2 cancers, 38.5%/9.8% of 379 pT 3a cancers, 43.5%/8.9% of 237 pT 3b cancers, 40.7%/14.8% of 27 pT 4 cancers, 39.1%/34.8% of 23 nodal metastases, 51.9%/33.3% of 27 bone metastases, and 45.5%/59.9% of 22 hormone refractory cancers (P < 0.0001 each). Both 8p deletions and 8q gains were also significantly associated with high Gleason grade and with each other (P < 0.0001 each). In primary tumors, 8p deletions were seen in only 27.3% of 1,882 cancers without 8q gain but in 57.4% of 122 tumors with 8q gain (P < 0.0001). Among cancers treated with radical prostatectomy, 8p deletions (P = 0.003) and 8q gains (P = 0.02) were associated with biochemical tumor recurrence. However, multivariate analysis (including prostate-specific antigen, pT/pN stage, Gleason score, and surgical margin status) did not reveal any statistically independent effect of 8p or 8q alterations on biochemical tumor recurrence.Conclusions: 8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application. Clin Cancer Res; 16(1); 56-64. ©2010 AACR.Prostate cancer is the most frequently diagnosed malignancy and the second most frequent cause of cancerrelated death among western males (1).Currently, clinical prediction tools rely solely on clinical (clinical stage), serologic (prostate-specific antigen), and histologic variables (Gleason grading; ref. 2).Because the development and progression of cancer is driven by molecular alterations, the analysis of molecular features may eventually allow better prediction of the behavior of individual cancers.Alterations on the DNA level would be especially suitable as prognostic markers. DNA alterations have the advantage of being less vulnerable to perioperative and postoperative ischemia or fixation procedures than RNA or proteins (3, 4). Deletions of 8p and gains of 8q are among the most frequent genomic alterations in prostate cancer. Several studies have proposed a relationship between 8p−/8q+ with adverse histopathologic findings (5-11). Studies suggesting associations with prostatespecific antigen progression, however, were limited to <100 cancers (12)(13)(14). Whereas considerable evidence points toward a role of chromosome 8 changes in prostate cancer biology, it is also evident that much larger patient cohorts are now needed to further cl...

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

Gammal¹,

Brüchmann²,

Zustin³

et al. 2010

Clinical Cancer Research

125

107

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“…In particular, gains of chromosome 7 are seen in locally advanced and/ or metastatic prostatic adenocarcinoma. 33 The neoplastic cells of prostatic adenocarcinoma are only rarely shed in urine and more often than not these tumors are Gleason score 8 or greater. These tumor cells are small and relatively bland, with moderate amounts of cytoplasm and a single prominent nucleolus.…”

Section: Discussionmentioning

confidence: 99%

The use of Urovysion™ fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder

et al. 2009

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Urovysiont fluorescence in situ hybridization (FISH) is a sensitive and specific test used to diagnose urothelial carcinoma in urine. It detects aneuploidy of chromosomes 3, 7 and 17, and loss of both 9p21 loci in malignant urothelial cells. We evaluated Urovysiont FISH in non-urothelial carcinoma involving bladder to determine its possible application to their diagnosis and surveillance. Paraffin blocks from 31 non-urothelial bladder carcinomas, 12 pure urothelial carcinomas and 2 urothelial carcinomas with squamous differentiation were tested according to Vysis-Abbot Laboratories' recommended standards. Cases included 15 primary squamous carcinoma, 2 urothelial carcinoma with squamous differentiation, 4 primary adenocarcinoma, 5 colonic, 4 prostatic and 1 cervical adenocarcinoma. Total 60% of squamous, 83% of pure urothelial, 100% of urothelial carcinoma with squamous differentiation and 100% of primary and secondary adenocarcinomas hybridized successfully; 2/10 (11%) squamous carcinomas and 11/14 (79%) primary and secondary adenocarcinomas were Urovysiont FISH-positive with primary adenocarcinomas accounting for 75% (3/4), colonic, 80% (4/5), prostatic, 75% (3/4) and cervical, 100% (1/1) positivity. Total 70% (7/10) of pure urothelial carcinomas and 100% (2/2) of urothelial carcinomas with squamous differentiation were Urovysiont FISH-positive. In conclusion, we found that chromosomal abnormalities tested for by Urovysiont FISH may be seen in non-urothelial carcinomas of bladder. These false-positive results were frequent in primary and secondary adenocarcinoma and rare in squamous carcinoma. This has significant implications for the accurate diagnosis and management of patients with urinary tract cancer. Urovysiont FISH cannot be used to definitively diagnose squamous carcinoma or adenocarcinoma nor can it be used to differentiate the two from urothelial carcinoma. However, it may be useful as a surveillance tool in established primary and secondary bladder adenocarcinoma. Cytopathologists and urologists should correlate Urovysiont FISH results with cytomorphology and clinical information.

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“…There is extra copy of 5p in M10 and 9q in M11, and gain of chromosome 8 material in M1 as q+ part. All these chromosomes are already implicated in prostate cancer (23)(24)(25)(26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles

Gu²,

Miki³

et al. 2007

Int J Oncol

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Abstract. Although epidemiological studies have suggested a positive correlation between environmental radon exposure and prostate cancer, the mechanism involved is not clear. In the present study, we examined the oncogenic transforming potency of α-particles using non-tumorigenic, telomeraseimmortalized human benign prostate epithelial cells. We report the malignant transformation of human benign prostate epithelial cells after a single exposure to 0.6 Gy dose of α-particles. Transformed cells showed anchorage-independent growth in soft agar and induced progressively growing tumors when transplanted into SCID mice. The tumors were characterized histologically as poorly differentiated adenocarcinomas. The cell line derived from tumor (SCID 5015), like the unirradiated cells, expressed cytokeratin 5, 8 and 18, NKX3.1 and AMACR. The malignant cells showed increased secretion of MMP2.Stepwise chromosomal changes in the progression to tumorigenicity were observed. Chromosome abnormalities were identified in both irradiated and tumorigenic cells relative to the non-irradiated control cells. Prominent changes in chromosomes 6, 11 and 16, as well as mutations and deletions of the p53 gene were observed in the tumor outgrowth and tumor cells. These findings provide the first evidence of malignant transformation of human benign prostate epithelial cells exposed to a single dose of α-particles. This model provides an opportunity to study the cellular and molecular alterations that occur in radiation carcinogenesis in human prostate cells. IntroductionIonizing radiation can cause as well as cure human cancers. There is abundant evidence that α-particles are potent carcinogens. Exposure of the lung to α-emitting radon progeny represents the largest component of background radiation to the US general public (1). Epidemiological studies have shown that uranium miners exposed to high levels of radon progeny show the largest number of radiation induced lung cancers found in any exposed population (2,3). The US Environmental Protection Agency has estimated that the number of radon related lung cancer deaths amounts to ~21,000 annually (4). Furthermore, plutonium ingestion in experimental animals has also highlighted the extreme effectiveness of α-particles in tumor induction (5). The relative short range and high linear energy transfer (LET) nature of α-particles that characterize their high relative biological effectiveness in lung cancer induction among uranium miners and people who lived in high radon background areas might also account for their effectiveness in the treatment of cancer.Carcinoma of the prostate is the most common male cancer in the United States. Interstitial brachytherapy using radium seeds that decay to emit predominantly γ-rays has been used in the treatment of localized lesions. More recently, targeted α therapy, using an α-particle emitting radioisotope such as 213 Bi to label monoclonal antibodies that are specific for prostate tissues has gained considerable attention (6,7). These studies have shown t...

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Chromosomal changes in prostate cancer: A fluorescence in situ hybridization study

Cited by 24 publications

References 25 publications

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

The use of Urovysion™ fluorescence in situ hybridization in the diagnosis and surveillance of non-urothelial carcinoma of the bladder

Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles

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