Loss of p53 and c-myc overrepresentation in stage T2-3 N1-3M0 prostate cancer are potential markers for cancer progression

Junqi Qian, Kiyoshi Hirasawa, David G. Bostwick, Erik J. Bergstralh, Jeff M. Slezak, Karl L. Anderl, Thomas J. Borell, Michael M. Lieber, Robert Brian Jenkins

Research output: Contribution to journalArticle

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Abstract

To determine whether genetic changes are markers of cancer progression and patient survival in Stage T2-3N1-3M0 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 = 4.0, P = .04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T2-3N1-3M0 prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T2-3N1-3M0 prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalModern Pathology
Volume15
Issue number1
DOIs
StatePublished - 2002

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Prostatic Neoplasms
Lymph Nodes
Neoplasm Metastasis
Neoplasms
Control Groups
Neoplasm Grading
Fluorescence In Situ Hybridization
Odds Ratio
Carcinoma
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 7
Survival
Genetic Heterogeneity
Centromere
Prostatectomy
Lymph Node Excision
Genetic Markers
Recurrence

Keywords

  • 7q31
  • 8p22
  • C-myc
  • FISH
  • Metastasis
  • P53
  • Prostate

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Loss of p53 and c-myc overrepresentation in stage T2-3 N1-3M0 prostate cancer are potential markers for cancer progression. / Qian, Junqi; Hirasawa, Kiyoshi; Bostwick, David G.; Bergstralh, Erik J.; Slezak, Jeff M.; Anderl, Karl L.; Borell, Thomas J.; Lieber, Michael M.; Jenkins, Robert Brian.

In: Modern Pathology, Vol. 15, No. 1, 2002, p. 35-44.

Research output: Contribution to journalArticle

Qian, J, Hirasawa, K, Bostwick, DG, Bergstralh, EJ, Slezak, JM, Anderl, KL, Borell, TJ, Lieber, MM & Jenkins, RB 2002, 'Loss of p53 and c-myc overrepresentation in stage T2-3 N1-3M0 prostate cancer are potential markers for cancer progression', Modern Pathology, vol. 15, no. 1, pp. 35-44. https://doi.org/10.1038/modpathol.3880487
Qian, Junqi ; Hirasawa, Kiyoshi ; Bostwick, David G. ; Bergstralh, Erik J. ; Slezak, Jeff M. ; Anderl, Karl L. ; Borell, Thomas J. ; Lieber, Michael M. ; Jenkins, Robert Brian. / Loss of p53 and c-myc overrepresentation in stage T2-3 N1-3M0 prostate cancer are potential markers for cancer progression. In: Modern Pathology. 2002 ; Vol. 15, No. 1. pp. 35-44.
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abstract = "To determine whether genetic changes are markers of cancer progression and patient survival in Stage T2-3N1-3M0 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 = 4.0, P = .04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T2-3N1-3M0 prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T2-3N1-3M0 prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.",
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TY - JOUR

T1 - Loss of p53 and c-myc overrepresentation in stage T2-3 N1-3M0 prostate cancer are potential markers for cancer progression

AU - Qian, Junqi

AU - Hirasawa, Kiyoshi

AU - Bostwick, David G.

AU - Bergstralh, Erik J.

AU - Slezak, Jeff M.

AU - Anderl, Karl L.

AU - Borell, Thomas J.

AU - Lieber, Michael M.

AU - Jenkins, Robert Brian

PY - 2002

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N2 - To determine whether genetic changes are markers of cancer progression and patient survival in Stage T2-3N1-3M0 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 = 4.0, P = .04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T2-3N1-3M0 prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T2-3N1-3M0 prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.

AB - To determine whether genetic changes are markers of cancer progression and patient survival in Stage T2-3N1-3M0 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 = 4.0, P = .04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T2-3N1-3M0 prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T2-3N1-3M0 prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.

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