Interphase cytogenetics of prostatic adenocarcinoma and precursor lesions: Analysis of 25 radical prostatectomies and 17 adjacent prostatic intraepithelial neoplasias

Abstract

Twenty-five radical prostatectomy specimens were screened for the presence of numerical chromosome changes within the adenocarcinoma as well as 17 adjacent prostatic intraepithelial neoplasias (PIN) by means of interphase in situ hybridization (ISH) to routinely processed tissue sections. To this end a defined alfoid repetitive DNA probe set was used, specific for the centromeres of chromosomes 1, 7, 8, 10, 15, and Y. The cytogenetic information was correlated with histopathological and clinical features as well as with DNA ploidy. Numerical aberrations of at least one chromosome were shown in 13 of 25 cases (52%). Alterations of chromosome 8 and loss of the Y chromosome were the most frequent findings (both 20%), followed by loss of chromosomes 15 (16%) and 10 (12%). Gain of chromosome 7 was seen in 8% of cases. No aberrations of chromosomes 7, 8, 10, and 15 were found in the adjacent PIN lesions, whereas loss of the Y chromosome in both PIN and tumor occurred in two cases. Also, (low level) aneuploidy was observed in 76% of these PIN lesions. Ploidy of the carcinomas as assessed by ISH correlated well with ploidy measured by DNA flow cytometry (FCM; P < 0.02). Due to the more specific correspondence between ISH and tumor pathology, pathologic grade correlated with ISH aneuploidy (P < 0.05), whereas FCM ploidy did not. Furthermore, genetic heterogeneity within a tumor was seen, as judged by the focal appearance of chromosomal aberrations. Chromosomal alterations occurred in all grades and stages, although loss of chromosome 10, gain of chromosome 7, and aberrations of chromosome 8 tended to predominate in more advanced cancers.

Chromosomal changes during development and progression of prostate adenocarcinomas

“…Thus, a subset of PIN areas, irrespective of their differentiation into low-or high-grade PIN, exhibits a number of aberrations similar to invasive carcinoma. These CGH findings on PIN areas confirm for many of the chromosomal alterations earlier studies which investigated corresponding loci either with LOH (Macintosh et al, 1998;Saric et al, 1999) or FISH analysis (Alers et al, 1995;Qian et al, 1996). These data provide evidence for the biological significance of PINs and support the assumption that they represent premalignant lesions of prostate cancer.…”

“…At the histological level, PINs outside the invasive carcinoma are considered as premalignant lesions of prostate cancer (Bostwick and Brawer, 1987;Bonkhoff and Remberger, 1996). In the PIN-carcinoma-metastasis sequence, PIN areas are poorly characterized for chromosomal alterations because they appear as very small cell compartments which can be only studied utilizing either microdissection and subsequent molecular genetic techniques like CGH (Weber et al, 1998;Zitzelsberger et al, 1998;Kim et al, 1999) or FISH on paraffin sections (Alers et al, 1995;Qian et al, 1996;Jenkins et al, 1997). In this study, we were able to demonstrate cytogenetic changes in 5 lymph node metastases and 12 PIN areas from 6 different cases.…”

“…Application of CGH and fluorescence in situ hybridization (FISH) to primary tumours of prostatic adenocarcinomas revealed consistent changes on chromosomes 7, 8p, 10, 13q, 16, 17 and 18q (Brothman et al, 1994;Macoska et al, 1994;Matsuyama et al, 1994;Joos et al, 1995;Qian et al, 1995;Visakorpi et al, 1995;Bova and Isaacs, 1996;Cher et al, 1996;Huang et al, 1996;Deubler et al, 1997). However, cytogenetic changes in prostatic intraepithelial neoplasias (PIN) which are considered as premalignant lesions and which are often present besides the invasive tumour are only poorly characterized cytogenetically (Alers et al, 1995;Qian et al, 1995;Zitzelsberger et al, 1998). Methodological improvements of approaches combining microdissection and CGH analysis (Kuukasjärvi et al, 1997) were prerequisites for the analysis of such early chromosomal aberrations in premalignant cells of other tumours like cervical carcinoma (Heselmeyer et al, 1996), breast cancer (Aubele et al, 2000b) and oral malignant lesions (Weber et al, 1998).…”

High-grade prostatic intraepithelial neoplasia

“…23 Flutamide decreased the prevalence and extent of high-grade PIN and induced epithelial atrophy. 165 There is also evidence that cessation of flutamide resulted in return of high-grade PIN. 16,166 The results of 5-alpha-reductase (finasteride) treatment in high-grade PIN are controversial and the cumulative number of cases studied is probably too small to draw firm conclusions.…”

Identification of a high frequency of chromosomal rearrangements in the centromeric regions of prostate cancer patients

“…Regarding chromosome 7, 7q karyotype was found in all groups and a few of the control group also showed them. Cytogenetic study and FISH studies indicated a gain of chromosome 7 in a substantial number of prostate cancers (Alers et al, 1995;van Dekken et al, 2000), and this gain was associated with higher tumour grade, advanced pathological stage and early prostate cancer death (described as a high Gleason score) (Takahashi et al, 1995). PCR analysis of LOH on prostate cancer indicated a common focus of deletion mapping to 7q31.1-31.2 (Zenklusen et al, 1994).…”