An evaluation of the markers p53 and Ki‐67 for their predictive value in prostate cancer

Uzoaru, Ikechukwu; Rubenstein, Marvin; Mirochnik, Yelena; Slobodskoy, Leonid; Shaw, Michael J.; Guinan, Patrick

doi:10.1002/(sici)1096-9098(199801)67:1<33::aid-jso7>3.3.co;2-b

Cited by 8 publications

(11 citation statements)

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“…Similarly, in breast cancer, Ki‐67 PI was found to independently predict survival and tumor recurrence 7,13. Nevertheless, the prognostic role of Ki‐67 remains controversial, because some studies have concluded that Ki‐67 PI does not predict clinical outcome in various cancer types, including prostate and breast cancer 14–18.…”

Section: Introductionmentioning

confidence: 99%

Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland—A review of current recommendations

et al. 2010

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Cutaneous squamous cell carcinoma (SCC) of the head and neck may metastasize in up to 5% of patients, with the parotid lymph nodes the most frequent site for spread. Metastases frequently show delayed presentation after the primary cancer had been treated. The optimum treatment should be surgery followed by adjuvant radiotherapy, with an appropriate parotidectomy, and preservation of the facial nerve if not involved by tumor and treatment to the neck. In a clinically N0 neck, levels I to III should be cleared for facial primaries, levels II to III for anterior scalp and external ear primaries, and levels II to V for posterior scalp primaries. Approximate 5-year disease-specific survival (DSS) after treatment was 70% to 75%. Patients with immunosuppression, in particular transplant recipients, are at high risk of developing aggressive metastatic cutaneous SCC. Modifications of the staging systems have demonstrated the prognostic benefits of accurately staging parotid and/or neck nodal disease.

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Section: Introductionmentioning

confidence: 99%

Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland—A review of current recommendations

et al. 2010

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“…Most of them suggest that immunohistochemical p53 positivity increases with high grade, advanced stage and peripheral zone origin, 6 and suggested that nuclear p53 accumulation may correlate with poor prognosis after radical prostatectomy, 7 external beam radiation 8 and unfavorable clinical courses in conservatively managed patients 9 but these data were not confirmed in other studies. 10,11 As TP53 testing on the DNA level is more labor intensive than IHC, there are only few published studies analyzing sets of 18-103 patients and reporting divergent frequencies of TP53 mutations (3-40%) 12 and deletions or loss of heterozygosity (10-60%). 13,14 Studies analyzing the clinical impact of TP53 gene deletions or combinations of deletions and p53 protein alterations in large patient cohorts are thus lacking.…”

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confidence: 99%

Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer

Kluth

Harasimowicz

Burkhardt

et al. 2014

Intl Journal of Cancer

101

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Despite a multitude of p53 immunohistochemistry (IHC) studies, data on the combined effect of nuclear p53 protein accumulation and TP53 genomic inactivation are lacking for prostate cancer. A tissue microarray including 11,152 prostate cancer samples was analyzed by p53 IHC and fluorescence in situ hybridization. Nuclear p53 accumulation was found in 10.1% of patients including 1.4% with high-level and 8.7% with low-level immunostaining. TP53 sequencing revealed that 17 of 22 (77%) cases with high-level p53 immunostaining, but only 3% (1 of 31) low-level p53 cases carried putative dominantnegative mutations. TP53 deletions occurred in 14.8% of cancers. Both deletions and protein accumulation were linked to unfavorable tumor phenotype and prostate specific antigen (PSA) recurrence (p < 0.0001 each). The combination of both methods revealed subgroups with remarkable differences in their clinical course. Tumors with either TP53 deletion (14%) or lowlevel p53 positivity (8.7%) had identical risks of PSA recurrence, which were markedly higher than in cancers without p53 alterations (p < 0.0001). Tumors with both p53 deletion and low-level p53 positivity (1.5%) had a worse prognosis than patients with only one of these alterations (p < 0.0001). Tumors with strong p53 immunostaining or homozygous inactivation through deletion of one allele and disrupting translocation involving the second allele had the worst outcome, independent from clinical and pathological parameters. These data demonstrate a differential clinical impact of various TP53 alterations in prostate cancer. Strong p53 immunostaining-most likely accompanying dominant negative or oncogenic p53 mutation-has independent prognostic relevance and may thus represent a clinical useful molecular feature of prostate cancer.Dysregulation of the p53 tumor suppressor belongs to the most frequent genetic alterations in malignant tumors. Reduced p53 function compromises cellular programs inducing apoptosis in DNA damaged cells and consequently enables tumor progression through acquisition of additional genetic changes. Mechanisms for TP53 inactivation include functionally relevant point mutations of the gene as well as gross chromosomal alterations, mostly 17p deletions. Disrupting breaks of the TP53 gene have only recently been described as an alternative mechanism for p53 inactivation. 1 Furthermore, at least certain p53 mutations can exhibit oncogenic properties through mutation-specific protein interactions that may be independent of the physiological gene function. For example, transgenic mice with particular p53 mutations develop a spectrum of primary cancers and metastases that is more aggressive and phenotypically different from those observed in mice with a p53-null allele. 2 Irrespective of their functional consequences, tumorigenic p53 mutations frequently accompany markedly increased levels of altered p53 protein in affected cells. 3 Immunohistochemistry (IHC) is thus commonly used to detect p53-mutated cancers.In prostate cancer, p53 alterations are less c...

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“…The 11 nondiploid tumors had a higher mean Ki67-LI. Coetzee et al [24], Cher et al [23], and Uzoaru et al [25] also reported associations between Ki67-LIs and DNA-ploidy. These results indicate that the parameters of Ki67-LI and DNA-ploidy are significantly, albeit weakly, related.…”

Section: Discussionmentioning

confidence: 94%

“…Although such histograms provide an approximation of the fraction of cells in S phase (SPF), the Ki-67 labeling index (Ki67-LI) is a more functional estimate of proliferation. The relationships between Ki67-LI and the DNA content parameters of DNA-ploidy and SPF are poorly documented for prostate cancer [23][24][25]. In addition, a number of reports indicate that Ki67-LI is significantly related to prostate cancer patient outcome after radical prostatectomy or androgen ablation therapy [26][27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy

et al. 1999

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BACKGROUND Our purpose was to evaluate the relationship of Ki‐67 labeling index (Ki67‐LI) to deoxyribonucleic acid (DNA) ploidy, S phase fraction (SPF), other clinical prognostic factors, and clinical outcome for patients with prostate cancer treated by external beam radiotherapy. METHODS Tissue was retrieved from 42 patients who underwent transurethral resection of the prostate before treatment with external beam radiotherapy between 1987–1993. DNA histogram profiles were classified as diploid (diploid + near‐diploid) and nondiploid (tetraploid + aneuploid). Immunohistochemical staining of Ki‐67 by the MIB‐1 monoclonal antibody was used to calculate Ki67‐LI. Median patient follow‐up was 62 months. Treatment failure was defined as two consecutive rises in serum prostate‐specific antigen (PSA) or clinical evidence of disease recurrence. RESULTS The mean and median Ki67‐LIs were 3.1 and 2.4, respectively (range, 0–12.4). Mean Ki67‐LI values were significantly associated with higher stage, Gleason score, and pretreatment PSA. Nondiploid tumors had significantly higher Ki67‐LIs, as did patients who failed radiotherapy over the follow‐up period. SPF was not significantly correlated with Ki67‐LI. As a categorical variable, the most significant relationships were seen when Ki67‐LI was subdivided into thirds around the median (Ki67‐LI ≤1.5%, Ki67‐LI >1.5–3.5%, and Ki67‐LI >3.5%). This trichotomous variable correlated significantly with pretreatment PSA (P = 0.0008), tumor stage (P = 0.016), Gleason score (P = 0.024), and treatment failure (P = 0.0015), but not with DNA‐ploidy (P = 0.15). In actuarial univariate analyses, Ki67‐LI appeared to be a more significant predictor of patient outcome (P = 0.003) than DNA‐ploidy (P = 0.035). CONCLUSIONS The Ki67‐LI correlated with known prognostic factors such as pretreatment PSA, tumor stage, and Gleason score, and was also weakly related to DNA‐ploidy. In comparison to DNA‐ploidy, Ki67 LI seems to be a better correlate of treatment outcome. Prostate 41:166–172, 1999. © 1999 Wiley‐Liss, Inc.

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An evaluation of the markers p53 and Ki‐67 for their predictive value in prostate cancer

Cited by 8 publications

References 0 publications

Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland—A review of current recommendations

Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland—A review of current recommendations

Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer

Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy

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