Independent origin of multiple foci of prostatic intraepithelial neoplasia

Bostwick, David G.; Shan, Ailin; Qian, Junqi; Darson, Micheal F.; Maihle, Nita J.; Jenkins, Robert B.; Liu, Cheng

doi:10.1002/(sici)1097-0142(19981101)83:9<1995::aid-cncr16>3.0.co;2-2

Cited by 171 publications

(101 citation statements)

References 21 publications

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“…Using PCR, ISH, and DNA ploidy techniques, similar intraglandular and intratumoral heterogeneity has been reported (12,24,40,41). Thus, the size of a cancer focus and its degree of histologic dedifferentiation may not reflect the extent of its genetic derangement (12,22,24,40,41). These results also indicate that without broad and systematic scrutiny of all neoplastic foci in a prostate, significant genetic changes will not be detected (12).…”

Section: Figurementioning

confidence: 72%

“…However, FISH analysis showed that some small low-grade tumor foci had a high frequency of genetic changes by FISH, whereas concurrent dominant high-grade tumor foci were normal, which indicates that small cancers can have significant alterations (12,22). Using PCR, ISH, and DNA ploidy techniques, similar intraglandular and intratumoral heterogeneity has been reported (12,24,40,41). Thus, the size of a cancer focus and its degree of histologic dedifferentiation may not reflect the extent of its genetic derangement (12,22,24,40,41).…”

Section: Figurementioning

confidence: 89%

“…For example, using the laser microdissection technique, Emmert-Buck et al (10) identified LPL loss in 91% of prostate cancer and in 63% of its precursor, prostatic intraepithelial neoplasia (PIN). In addition, Bostwick et al (24) found LPL loss in 50% of prostate cancer and in 41% of PIN. In this study, we found that Ͼ80% of Stage T 2-3 N 1-3 M 0 prostate cancer had loss of the LPL locus, but this loss was not associated with cancer progression.…”

Section: Figurementioning

confidence: 99%

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

et al. 2002

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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

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Section: Figurementioning

confidence: 72%

Section: Figurementioning

confidence: 89%

Section: Figurementioning

confidence: 99%

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

et al. 2002

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“…These data suggest that prostatic carcinogenesis may be attributed to a field effect, supported by recent molecular evidence that multiple prostate cancers arise independently. 30,31 Our finding of frequent multifocality and bilaterality in small-volume prostate cancer is important for this reason. The fact that these patients have developed multifocal tumors even with a very low total tumor volume suggests that the field cancerization mechanism of carcinogenesis is already in effect 30,31 and that other tumors will likely arise in the future if these cancers are left untreated.…”

Section: Discussionmentioning

confidence: 91%

“…30,31 Our finding of frequent multifocality and bilaterality in small-volume prostate cancer is important for this reason. The fact that these patients have developed multifocal tumors even with a very low total tumor volume suggests that the field cancerization mechanism of carcinogenesis is already in effect 30,31 and that other tumors will likely arise in the future if these cancers are left untreated. Based on our findings and those of Epstein et al, 29 it is not unreasonable to speculate that some of these future tumors might contain high-grade foci.…”

Section: Discussionmentioning

confidence: 92%

Anatomic distribution and pathologic characterization of small-volume prostate cancer (<0.5 ml) in whole-mount prostatectomy specimens

et al. 2005

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Some investigators consider small-volume prostate cancer (0.5 ml or less) without Gleason pattern 4/5 elements as clinically insignificant. The objective of this study was to characterize the anatomic distribution and pathologic features of small tumors (aggregate volume of 0.5 ml or less) in whole-mount prostatectomy specimens. Between 1999 and 2003, 371 consecutive patients underwent radical prostatectomy at the Indiana University Hospitals for localized prostate cancer. Patients who received hormonal or radiation therapy prior to the surgery were excluded from the study. A total of 62 specimens with total tumor volume of 0.5 ml or less were identified and included in this study. All specimens were embedded and whole-mounted. Tumor volume was measured using the grid method. The mean age at the time of surgery was 59 years (median, 61 years; range, 37-72 years). The mean preoperative prostate-specific antigen (PSA) was 6.5 ng/ml (range: 0.3-18 ng/ml). The mean prostate weight was 53 g (range: 16-132 g). The mean tumor volume was 0.29 ml (median, 0.35 ml; range, 0.02-0.48 ml). Tumor multifocality and bilaterality were present in 69 and 37% of cases, respectively. Three (5%) had positive surgical margins. The largest tumor was located in the peripheral zone, transitional zone, and central zone in 79, 16, and 5% of cases, respectively. The largest tumor was located in the anterior prostate in 10 cases (16%) and in the posterior prostate in 52 cases (84%). The distribution of Gleason scores was 5 (12 cases, 19 %), 6 (40 cases, 65 %), and 7 (10 cases, 16 %). One case had a primary Gleason pattern 4. None had extraprostatic extension, seminal vesicle invasion, or lymph node metastasis. Small-volume prostate cancers are often multifocal and bilateral, with predilection for the peripheral zone. Of these small-volume cases, 16% had Gleason pattern 4 and might, therefore, be clinically significant.

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p53 Protein overexpression is associated with increased cell proliferation in patients with locally recurrent prostate carcinoma after radiation therapy

Liu

Sebo

Cheville

et al. 1999

Cancer

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BACKGROUND The biologic changes in recurrent prostate carcinoma following radiation therapy are not fully understood. The authors sought to determine the level of p53 protein overexpression and its association with cellular proliferation (Ki‐67 labeling index), glutathione S‐transferase‐π (GST‐π) expression, and other clinical pathologic findings in patients with locally persistent prostate carcinoma after radiation therapy. METHODS The authors investigated p53 nuclear accumulation, cellular proliferation activity (Ki‐67 labeling index by digital image analysis), and GST‐π expression in 55 patients with persistent or recurrent prostate carcinoma after radiation therapy. All patients underwent salvage radical prostatectomy and bilateral pelvic lymphadenectomy following irradiation failure. The interval from radiation therapy to cancer recurrence ranged from 6 months to 17 years (mean, 3.8 years). Age at surgery ranged from 51 to 78 years (mean, 65 years). Mean follow‐up after surgery was 5.7 years (range, 1–13 years). RESULTS p53 protein overexpression was associated with increased cell proliferation (Spearman rank correlation coefficient = 0.29, P = 0.03). A substantial proportion (62%) of recurrent cancer also showed GST‐π immunoreactivity. No apparent correlation was observed between p53 protein overexpression, cellular proliferation (Ki‐67 labeling index), or GST‐π expression and Gleason score, pathologic stage, DNA ploidy, or patient outcome. There was an inverse correlation between GST‐π expression and Gleason score (P = 0.06). The majority of prostate carcinomas (95%) were proliferative (mean Ki‐67 labeling index, 7.0; range, 0–20), whereas concurrent prostatic intraepithelial neoplasia (PIN) had a lower Ki‐67 labeling index (mean, 3.1; range, 0–11.5). Nineteen of 28 (68%) concurrent PIN demonstrated p53 immunoreactivity. A trend toward adverse clinical outcome was observed in patients with a higher Ki‐67 labeling index in recurrent cancer. CONCLUSIONS In this study cohort selected for salvage prostatectomy, recurrent cancers were biologically aggressive following radiation therapy. Whether this represents selective persistence and regrowth of prognostically unfavorable tumor clonogens or stepwise clonogenic progression is uncertain. Further investigation is needed to elucidate the correlation between p53 overexpression and the presence of other biologic changes after radiation therapy. Cancer 1999;85:1293–9. © 1999 American Cancer Society.

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Independent origin of multiple foci of prostatic intraepithelial neoplasia

Cited by 171 publications

References 21 publications

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

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

Anatomic distribution and pathologic characterization of small-volume prostate cancer (<0.5 ml) in whole-mount prostatectomy specimens

p53 Protein overexpression is associated with increased cell proliferation in patients with locally recurrent prostate carcinoma after radiation therapy

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