p53 expression is of independent predictive value in lymph node-negative breast carcinoma

Fresno, Manuel; Molina, Ricardo; Rio, M. J. Perez Del; Alvarez, Salomé; Díaz-Iglesias, J.M; García, Isabel; Herrero, Ana

doi:10.1016/s0959-8049(97)00096-8

Cited by 19 publications

(13 citation statements)

References 34 publications

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“…The same negative results that were obtained in the current study were shown in 4 of 10 studies concerning lymph node status, 81,90 -92 in 4 of 8 studies concerning patient age, 72,91,93,94 and in 3 of 11 studies concerning tumor size. 58,94,95 The same positive results that were obtained in the current study were found in 2 of 3 studies concerning mitotic activity, 95,96 58,72,77,81,84,87,91,92,95,[97][98][99] and in both studies concerning SPF. 72,95 In the current study, Ki-67 was not correlated with survival, p21 and cyclin A were correlated with survival of any type, and p53 was correlated with MFS.…”

Section: Discussionsupporting

confidence: 89%

“…Unexpectedly, we did not evidence any correlation with SPF or mitotic index. The same negative results that we found were reported in the literature in 7 of 12 studies concerning patient age, [45][46][47][48][49][50][51] in 9 of 22 studies concerning lymph node status, 45,47,50 -56 in 7 of 19 studies concerning tumor size, 45,47,49,51,54,57,58 and in 4 of 5 studies concerning p21. 59 -62 Our results were at odds with reports in the literature, including 12 of 12 studies that showed positive correlations were between Ki-67 and mitotic activity 45,47,54,[62][63][64][65][66][67][68][69][70] and 8 of 9 studies that showed a correlation between Ki-67 and SPF.…”

Section: Discussionsupporting

confidence: 88%

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Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Michels

Duigou

Marescaux

et al. 2003

Cancer

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BACKGROUNDBetween January 11, 1991 and January 8, 1992, 104 patients with previously untreated, invasive, primitive breast carcinoma were admitted to the authors' hospital.METHODSFor each patient, flow cytometry DNA analyses on frozen samples and on immunohistochemical staining were performed, including Ki‐67, cyclin A, p53, and p21waf1 (p21), with assessment of the percentages of positive nuclei were assessed. Correlations with classic clinicopathologic data and survival (overall, metastasis free, or recurrence free) and a multivariate analysis were performed.RESULTSAfter a multivariate analysis according to a Cox model that was stratified by age, tumor size, tumor grade, lymph node status, and receptor status, among the factors studied, the presence of p21 was the unique remaining prognostic factor for patients with invasive breast carcinoma. Because of the lack of a correlation between p21 and proliferative factors (Ki‐67, S‐phase, and cyclin A), the authors combined p21 with those markers and found that, for the different combinations, after statistical analysis, only p21 combined with S‐phase or with cyclin A and lymph node status were salient survival prognostic factors.CONCLUSIONSImmunohistochemical study of proteins involved in the cell cycle and assessment of proliferative activity using flow cytometric DNA analysis aided the authors in singling out correlations of cyclin A and S‐phase, along with p21, with metastasis free survival and overall survival in patients with invasive breast carcinoma. These promising results will require confirmation in a larger series of patients. Cancer 2003;97:1376–86. © 2003 American Cancer Society.DOI 10.1002/cncr.11209

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 88%

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Michels

Duigou

Marescaux

et al. 2003

Cancer

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“…Regarding OS (9472 patients), of all 35 studies, subgroup analysis was possible in nine studies with nodenegative patients (1996 patients) (Jensen et al, 1995;Weikel et al, 1995;Bevilacqua et al, 1996;Brown et al, 1996;Domagala et al, 1996;Fresno et al, 1997;Rudolph et al, 1999a;Trihia et al, 2003;Erdem et al, 2005), in four with node-positive patients (857 patients) Domagala et al, 1996;Gonzalez et al, 2003;Trihia et al, 2003) and in two that included only untreated patients (node-negative and node-positive) (284 patients) (Pinder et al, 1995;Bevilacqua et al, 1996).…”

Section: Characteristics Of the Studiesmentioning

confidence: 99%

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

et al. 2007

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The Ki-67 antigen is used to evaluate the proliferative activity of breast cancer (BC); however, Ki-67's role as a prognostic marker in BC is still undefined. In order to better define the prognostic value of Ki-67/MIB-1, we performed a meta-analysis of studies that evaluated the impact of Ki-67/MIB-1 on disease-free survival (DFS) and/or on overall survival (OS) in early BC. Sixty-eight studies were identified and 46 studies including 12 155 patients were evaluable for our meta-analysis; 38 studies were evaluable for the aggregation of results for DFS, and 35 studies for OS. Patients were considered to present positive tumours for the expression of Ki-67/MIB-1 according to the cut-off points defined by the authors. Ki-67/MIB-1 positivity is associated with higher probability of relapse in all patients (HR ¼ 1.93 (95% confidence interval (CI): 1.74 -2.14); Po0.001), in node-negative patients (HR ¼ 2.31 (95% CI: 1.83 -2.92); Po0.001) and in node-positive patients (HR ¼ 1.59 (95% CI: 1.35 -1.87); Po0.001). Furthermore, Ki-67/MIB-1 positivity is associated with worse survival in all patients (HR ¼ 1.95 (95% CI: 1.70 -2.24; Po0.001)), node-negative patients (HR ¼ 2.54 (95% CI: 1.65 -3.91); Po0.001) and node-positive patients (HR ¼ 2.33 (95% CI: 1.83 -2.95); Po0.001). Our meta-analysis suggests that Ki-67/ MIB-1 positivity confers a higher risk of relapse and a worse survival in patients with early BC.

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“…Breast carcinomas in young women have been reported to express fewer estrogen receptors (ER), 10,[15][16][17][18] to have a higher index of proliferation 8,19 -22 and to be more likely to exhibit an abnormal nuclear accumulation of mutant p53 protein 8,[23][24][25][26] than those in older women. Also, comparisons of the pathology of breast carcinomas have demonstrated that there is a greater proportion of high-grade carcinomas in young women (younger than 40 years) 27,28 and that special histologic types of invasive carcinoma (e.g., mucinous and papillary carcinomas) with more favorable prognoses than the more common infiltrating ductal carcinoma are more prevalent in older than younger populations.…”

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confidence: 99%

Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre‐ and postmenopausal women

Talley

Grizzle

Waterbor

et al. 2001

Intl Journal of Cancer

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Breast cancers in younger, premenopausal women are more likely to exhibit an adverse prognostic profile (including negative steroid hormone receptors and a high rate of cellular proliferation) and poor outcome than breast cancers in postmenopausal women. It has been hypothesized that this adverse prognostic profile is a result of the higher histologic grade of breast cancers in pre-compared with post-menopausal women. To assess the association of expression of steroid hormone receptors and indicators of proliferation while controlling for histologic grade, we identified 100 infiltrating ductal carcinomas from premenopausal women 45 years of age or younger and 100 from postmenopausal women 65 years of age or older. The carcinomas were selected so that the histologic grades (low versus high) were distributed equally between the 2 groups. Estrogen receptors (ER), progesterone receptors (PR), p27 Kip1 and Ki-67 (to measure rate of proliferation) were assessed by immunohistochemistry and compared between groups. Clinical information and survival data were also analyzed. ER content was lower and proliferation was higher in carcinomas in premenopausal women (p ‫؍‬ 0.048 and p ‫؍‬ 0.005, respectively). By univariate analysis, p27 Kip1 and PR were not different between the groups; however, in multivariate analysis, p27 Kip1 was higher in postmenopausal women, but only in a subgroup with highly proliferative carcinomas. Overall survival was similar in the pre-and postmenopausal women. Furthermore, low p27 Kip1 and African-American ethnicity predicted a poorer overall survival in the premenopausal, but not in the postmenopausal, women in our study. After controlling for histologic grade, a lower expression of ER and a higher proliferative index were detected in breast carcinomas in premenopausal women. Therefore, some prognostic indicators, such as ER and proliferative rate, may be more closely associated with menopausal status than histologic grade. Our data also suggest that some prognostic factors are not equally effective as predictors of survival in pre-and postmenopausal women. Prognosis in women with breast cancer has been reported to differ according to age and menopausal status. Studies examining this issue have varied in design, age categorization and outcome measures. A few large population-based studies and more limited analyses 1-5 have indicated that women under the ages of 30 -40 years have a worse prognosis. Some retrospective studies have attempted to explain the less favorable outcome in younger women and have reported that breast cancers in younger women exhibit more adverse characteristics, including a high clinical stage at diagnosis, high histologic grade, lack of steroid hormone receptors and increased proliferation. 6 -9 Multivariate analyses to assess associations of age and menopausal status with other clinical and pathologic characteristics have not consistently retained either variable as an independent adverse prognosticator, 8 although several multivariate analyses have indicated that young ag...

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p53 expression is of independent predictive value in lymph node-negative breast carcinoma

Cited by 19 publications

References 34 publications

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre‐ and postmenopausal women

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