Interphase cytogenetics of prostate cancer: fluorescence in situ hybridisation (FISH) analysis of Japanese cases

Abstract

Summary No numerical aberration of chromosomes that might be specific for prostate cancer has so far been established. We used fluorescence in situ hybridisation (FISH) with centromere-specific probes for chromosomes 7, 8, 17, X and Y to establish the distribution of centromere copy numbers in frozen-stored or freshly prepared samples of benign prostate hypertrophy (BPH) and to detect numerical aberrations of these chromosomes in 28 prostate cancers from Japanese men. There was no significant difference in the data of centromere copy numbers between fresh and frozen-stored tissue. The most common aberration in prostate cancers was a gain of chromosome 8 (57%), with numerical aberration of chromosome 7 being the second most frequent anomaly (50%). Numerical aberration of chromosome 7 is most significantly associated with a higher Gleason score (GS) (P<0.005) or with lymph node metastasis (P<0.001). Numerical aberration of several chromosomes, including chromosomes 7 and/or 8, was common in aggressive prostate cancers. Loss of chromosome Y was detected in only 4% of cases. FISH analysis thus proved to be a useful method for detecting numerical aberrations of individual chromosomes, with application to touch preparations of frozenstored tissue having the advantage of exact sampling of cancer foci. The results suggest that numerical aberration of chromosome 7 is associated with aggressive tumour behaviour and poor prognosis of patients with prostate cancer. The association between genetic change and chromosomal abnormality should be studied in detail.Keywords: interphase cytogenetics; fluorescence in situ hybridization; prostate cancer Fluorescence in situ hybridisation (FISH) has been used to hybridise specific nucleic acid sequences with complemental DNA fragments, revealing their location on chromosomes and their copy numbers (Trask et al., 1990). Compared with conventional metaphase cytogenetics or karyotyping analysis, FISH allows more rapid enumeration of specific chromosomes and detection of chromosomal alterations even in interphase nuclei (interphase cytogenetics) as well as in metaphase nuclei (Cremer et al., 1986;Pinkel et al., 1986). This technique does not always require tissue culturing and can be applied to solid tumours (Persons et al., 1993;Devilee et al., 1988) and even formalin-fixed, paraffin-embedded tissues (Micale et al., 1993;Persons et al., 1994). FISH has been demonstrated to be more sensitive than flow cytometry (FCM) for detecting aneuploidy (Takahashi et al., 1994;Visakorpi et at., 1994), and the methodology can detect numerical aberrations of individual chromosomes at levels impossible with FCM and image cytometry (ICM). FCM also has limitations regarding minor quantitative DNA changes (Hopman et al., 1990). While the application of FISH to studies of the association between DNA aneuploidy and prognosis has attracted attention, no numerical aberration of any chromosome which might be specific for prostate cancer has so far been established. Furthermore, it is unclear whether the numeri...

Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients

“…Gains of chro- In particular, gain of chromosome 7 and/or 8 has been reported to be one of the most common numerical aberrations (2.9-66.0%, and 5.7-66.7%, respectively) and is associated with aggressive tumor behavior in prostate cancers [8,9,20,21,24]. Gain of chromosome X has also been recently reported in 40.0-45.7% of prostate cancers [8].…”

“…The c-myc gene encodes a DNA binding protein that is reported to be associated with cell proliferation [17] and programmed cell death [18,19]. Several cytogenetic studies in Western countries have suggested that gain of chromosome 8 and amplification of the c-myc gene are potential markers of prostate cancer progression [8,9,14,20,21].…”

Numeric chromosome aberrations in prostate cancer detected by in situ hybridization

“…T u m o r Mostofi grade was strongly associated with chromosome copy number for chromosomes 7 Table 2).…”

Cytogenetic Analysis of Prostate Carcinoma Patients

“…Satoru Takahashi et al, 13 reported that numeric changes of chromosomes 7, 8, X, and Y are common in prostate carcinoma. H Matsuura et al, 14 found in his study that out of 28 prostate cancers, the most common aberration in prostate cancers was a gain of chromosome 8 (57%), with numerical aberration of chromosome 7 being the second most frequent anomaly (50%). Robert B. Jenkins et al, 15 studied 25 prostate specimens, of which six tumours had no apparent anomaly for any chromosome 7 probe.…”