Loss of p53 and c-myc Overrepresentation in Stage T2-3N1-3M0 Prostate Cancer are Potential Markers for Cancer Progression

Abstract

To determine whether genetic changes are markers of cancer progression and patient survival in Stage T 2-3 N 1-3 M 0 prostatic carcinoma, we compared 26 patients who died of tumor relapse after prostatectomy and lymphadenectomy (case group) with 26 matched patients who were alive at the time of the matched case's death (control group). Nine unmatched cases were also included in this study. In 37 cases, paired primary tumors (119 foci) and lymph node metastases (114 foci) were available for study. Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, and 17 and region-specific probes for D7S486 (7q31), c-myc (8q24), LPL (8p22), and p53 (17p13) was performed on available primary carcinomas and lymph node metastases. In primary tumor foci, ؉7q31, ؊8p22, ؉c-myc, substantial additional increases of myc (AI-c-myc), and ؊p53 were observed in 65%, 74%, 43%, 29%, and 31% of foci, respectively. AI-c-myc was strongly associated with higher cancer Gleason score (P ‫؍‬ .003). Heterogeneity of genetic changes was frequently observed among multiple cancer foci. Lymph node metastases of prostate cancer usually shared genetic changes with paired primary tumors. In addition, the genetic change pattern with ؊8p, ؉c-myc or AI-c-myc, ؉7q, and ؉p53 was slightly higher in lymph node metastases (22%) than in primary tumors (6%) (P ‫؍‬ .08). In matched case and control patients, simultaneous gain of 7q31 (؉7q31) and CEP7 (؉CEP7) was identified in 59% and 68% of specimens for case and control groups, respectively (P ‫؍‬ .48). Loss of 8p22 (؊8p22) was identified in 77% and 69% of specimens for case and control groups, respectively (P ‫؍‬ 1.0). Simultaneous gain of c-myc (؉c-myc) and CEP8 (؉CEP8) without overt additional increase of c-myc copy number relative to CEP8 copy number, was identified in 38% and 54% of specimens for case and control groups, respectively (P ‫؍‬ .27). AI-c-myc was identified in 54% and 23% of specimens for case and control groups, respectively (odds ratio ‫؍‬ 3.0, P ‫؍‬ .06). Loss of p53 (؊p53) was identified in 46% and 15% of specimens for case and control groups, respectively (odds ratio Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States (1). Patients with pelvic lymph node metastases of prostatic carcinoma, but no evidence of systemic progression are commonly classified as having Stage T 2-3 N 1-3 M 0 prostate cancer (2). These cancers have an indeterminate natural history (3). Choosing different types of therapy (radiation, surgery, or hormonal therapy) for these

HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis

“…The oncogene c-Myc enhances protein translation through transactivating diverse targets, such as initiation factors, ribosomal proteins, and rRNAs. Activation of c-Myc is found in a variety of cancers, including breast cancer, and its activation seems to be a surrogate marker for cancers (44)(45)(46)(47)(48)(49). The role of c-Myc in driving protein synthesis is in part attributed to promoting ribosome production through transcribing a number of ribosomal proteins (34)(35)(36).…”

Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays

“…Amplification of the c-myc locus 8q24 is linked to higher Gleason scores (Qian et al, 2002) and a poor prognosis (Sato et al, 1999;Tsuchiya et al, 2002). Concerning MYC protein expression, only two studies have been published for prostate cancer tissue so far.…”

Inflammation, prostatitis, proliferative inflammatory atrophy: ‘Fertile ground’ for prostate cancer development?

“…Moreover, additional increases of c-myc (AI-c-myc) have been associated with a higher Gleason score and poorer survival in men with Stage pT 3 n 0 M 0 prostate cancer (reviewed in ref. 40). In a study based on histopathological examination of surgical specimens from a cohort of 52 patients, Qian et al demonstrated that AI-c-myc was strongly associated with high Gleason score, and thus with prostate cancer progression, and proposed c-myc as a potential marker of survival in Stage T (2)(3) n (1-3) M (0) prostate cancer (40).…”