A comparison of proliferation markers and their prognostic value for women with endometrial carcinoma: Ki-67, proliferating cell nuclear antigen, and flow cytometric S-phase fraction

Nordström, Britta; Strang, Peter; Bergström, Reinhold; Nilsson, Sten; Tribukait, Bernhard

doi:10.1002/(sici)1097-0142(19961101)78:9<1942::aid-cncr15>3.0.co;2-y

Cited by 48 publications

(18 citation statements)

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“…This finding is not new. [15][16][17][18][19][20][21] However, the strength of our prospective study is that this is the first that presents 10-year results of flow cytometric DNA analysis from fresh tumor samples. In fact, it is known that histograms from paraffin-embedded material are less accurate than those from fresh tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, to improve the outcome of patients with endometrial cancer a new, more accurate prognostic assessment is mandatory to identify patients with high-risk disease. In recent years research focused on biological aspects of the tumor, such as DNA content, [8][9][10][11][12][13][14][15][16][17][18][19][20][21] protooncogenes, [22][23][24] and tumor-suppressor genes expression [25][26][27][28][29][30][31][32][33] that have been investigated as possible predictors of clinical outcome in endometrial cancer. The advantage of these parameters is that they are considered to provide objective and reproducible information.…”

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confidence: 99%

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Ten‐year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma

Susini

Amunni

Molino

et al. 2007

Cancer

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BACKGROUND.To improve the outcome of endometrial cancer patients, a more accurate prognostic assessment is mandatory. The aims of the study were to evaluate the role of flow cytometric DNA ploidy as an independent prognostic factor in patients with endometrial cancer and to verify if ploidy was able to distinguish patients with different prognosis into homogeneous subgroups for grade of differentiation and stage.METHODS.In a prospective study, DNA ploidy was evaluated from fresh tumor samples in 174 endometrial cancer patients who underwent surgery as the first treatment. Ploidy, as well as classical parameters, were analyzed in relation to the length of disease‐free survival and disease‐specific survival.RESULTS.DNA aneuploidy was found in 49 patients (28.2%). Patients with DNA‐aneuploid tumors had a significantly reduced disease‐free interval and disease‐specific survival (P < .0001). The 10‐year survival probability was 53.2% for DNA‐aneuploid patients and 91.0% for patients with DNA‐diploid tumors. By multivariate analysis DNA‐aneuploid type was the strongest independent predictor of poor outcome, followed by age and stage. Patients with DNA‐aneuploid tumor had a significantly higher risk ratio for recurrence (5.03) and death due to disease (6.50) than patients with DNA‐diploid tumors. Stratification by DNA‐ploidy within each group by grade of differentiation allowed identification of patients with significantly different outcome. In grade 2 tumors, 10‐year survival was 45.0% in aneuploid cases and 91.9% in diploid cases (P < .0001). Patients with advanced‐stage (>I) diploid tumor did significantly better than patients with stage I aneuploid tumor (P = .04).CONCLUSIONS.The presence of DNA‐aneuploid type in endometrial cancer identifies high‐risk cases among the patients considered ‘low risk’ according to stage and grade of differentiation. Cancer 2007. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Ten‐year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma

Susini

Amunni

Molino

et al. 2007

Cancer

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“…Geisler et al (37), in an earlier study on a series of 39 patients, had shown MIB-1 to be indicator of increased risk of recurrence. Nordstrom et al (38) found MIB-1/Ki-67 expression and S-phase fraction were significantly related to disease-specific survival in patients with endometrial carcinoma. Despite the methodological differences between these studies, all found MIB-1 to be an independent prognostic indicator of survival.…”

Section: Discussionmentioning

confidence: 99%

Markers of Proliferative Activity Are Predictors of Patient Outcome for Low-Grade Endometrioid Adenocarcinoma But Not Papillary Serous Carcinoma of Endometrium

et al. 2002

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On the basis of pathogenesis, two types of endometrial cancer can be recognized. Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogen stimulation, on a background of endometrial hyperplasia. Type 2 endometrial carcinomas are aggressive tumors that are not associated with hyperplasia or estrogen excess. The aim of this study is to evaluate the prognostic significance of tumor proliferative activity in early-stage endometrial cancer by using mitotic index and immunostaining, comparing Type 1 (endometrioid) and Type 2 (papillary serous carcinoma) tumors. The mitotic index, MIB-1, and p53 immunostaining in 39 tumors from patients with lowgrade Stage Ia or Ib endometrioid adenocarcinoma; as well as 23 tumors from patients with Stage I papillary serous carcinoma. In low-grade endometrioid adenocarcinoma, mitotic and MIB-1 indices were statistically significant independent prognostic indicators (P ‫؍‬ .004 and P ‫؍‬ .018, respectively), and both were strongly correlated with p53 expression (P ‫؍‬ .01 and P ‫؍‬ .006, respectively). The mean mitotic index was 5 mitoses/10 high-power fields, and mean MIB-1 index was 27.5%. There was no significant correlation between mitotic or MIB-1 indices and patient outcome or p53 expression in papillary serous carcinoma. The mean mitotic index was 31 mitoses/10 high-power fields, and mean MIB-1 index was 30.5% in these tumors. p53 expression and proliferative indices are strongly correlated in low-grade endometrioid adenocarcinoma. MIB-1 and mitotic indices are independent prognostic indicators in these tumors. Papillary serous carcinoma of endometrium is rapidly proliferative in tumors even at an early stage, and quantification of proliferative activity in these tumors does not allow prediction of patient outcome. KEY WORDS: Endometrial carcinoma, MIB-1, Mitotic index, p53, Papillary serous carcinoma, Proliferative activity. Mod Pathol 2002;15(4):365-371Endometrial cancer is the fourth most common malignancy in North American women. In the United States, there are 33,000 newly diagnosed cases and 4,000 deaths per year (1, 2). On the basis of the proposed dualistic model of endometrial carcinogenesis, there are two types of endometrial carcinoma that differ with regard to epidemiologic risk factors, histopathologic lesions, and molecular events (3). Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogenic stimulation. Low-grade endometrioid adenocarcinoma is the prototype of Type 1 endometrial carcinoma. Although most of these patients do well, recurrence and death due to disease can occur. Type 2 endometrial carcinomas are more aggressive tumors that are not associated with endometrial hyperplasia or estrogen excess. These tumors develop de novo in the atrophic endometrium of older postmenopausal women (4 -7). Papillary serous carcinoma of endometrium (PSCE) is the prototype of Type 2 endometrial carcinoma and is an uncommon aggressive variant of endometrial cancer. It accounts for 1-10% of cas...

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“…The effect of the mutation of PTEN remains controversial, since this has been found to be positively associated with prognosis, whereas the loss of expression and methylation of PTEN are negatively associated with prognosis (54). A high proliferative activity of tumor cells based on Ki-67 expression and the number of mitoses is associated with a poor prognosis in endometrial cancer; however, the multivariate survival analyses do not show concordant results, which may be due to technical differences in measuring Ki-67 (55,56). The loss of expression of Bcl-2 and the resultant reduced apoptosis are also associated with a poor prognosis (39).…”

Section: Biomarkers For Prognosis and Treatmentmentioning

confidence: 99%

Biomarkers in endometrial cancer: Possible clinical applications (Review)

et al. 2012

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Abstract. The number of cases of endometrial cancer has shown a tendency to increase in recent years. Endometrial cancer originates from the endometrium and is classified, based on the development mechanism, into types 1 and 2, which are responsive and non-responsive to estrogen, respectively, and have significantly different gene expression profiles. Studies of genes with abnormal expression in endometrial cancer have identified multiple oncogenes, tumor suppressors, mismatch repair genes, apoptosis-associated genes, levels of hormone receptors and DNA ploidy and aneuploidy as biomarkers of endometrial cancer. The use of these molecules and genes may facilitate accurate diagnosis and prognostic prediction and contribute to individualized treatment. Trials of drugs which target these biomarkers and searches for new biomarkers using cDNA microarrays and RT-qPCR are ongoing and it is likely that these findings can be translated to clinical use. Contents1. Introduction 2. Differences in biomarkers in subtypes of endometrial cancer 3. Oncogenes 4. Tumor suppressors 5. Mismatch repair genes and microsatellite instability 6. Other biomarkers 7. Biomarkers for prognosis and treatment 8. Conclusion IntroductionEndometrial cancer is the seventh most common cancer worldwide in women (1). The incidence differs depending on the region: in developed countries, 10-20 in 100,000 women have endometrial cancer, whereas the incidence is approximately one-tenth this level in developing countries. The number of cases is rapidly increasing in Japan. Obesity, nulliparity and the administration of tamoxifen have been identified as risk factors for endometrial cancer (2).In the last 10 years, numerous studies have aimed to identify tumor biomarkers. The US National Cancer Institute (NCI) defines a biomarker as ʻa biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or diseaseʼ. According to this definition, a biomarker includes not only the proteins normally used as tumor markers, such as CA-125, but also genes and chromosomes. Biomarkers of endometrial cancer that have been identified include the K-ras, HER2/neu, epithelial growth factor receptor (EGFR), phosphatidylinositol 3-kinase catalytic subunit (PI3KCA) and fibroblast growth factor receptor 2 (FGFR2) oncogenes; the phosphatase and tensin homolog (PTEN), p53, p21 and cyclin-dependent kinase inhibitor 2A (CDKN2A) cancer suppressor genes; the hMLH1, hMSH2, hMSH6, PMS1 and PMS2 mismatch repair genes; Ki-67, an index of cell proliferation; BCL2-associated X protein (Bax), an apoptosis promotor gene; Bcl-2, an apoptosis suppressor; expression levels of estrogen and progesterone receptors; microvascular density (MVD); and vascular endothelial growth factor A (VEGF-A), which are all indices of angiogenesis; expression changes in E/P-cadherin and β-catenin, which are associated with infiltration and metastatic capacity; and ploidy and aneuploidy of DNA. The characteristics and functions of each of these bioma...

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A comparison of proliferation markers and their prognostic value for women with endometrial carcinoma: Ki-67, proliferating cell nuclear antigen, and flow cytometric S-phase fraction

Abstract: BACKGROUND.The understanding of proliferation is a central issue in oncology. Sev-

Cited by 48 publications

References 36 publications

Ten‐year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma

Ten‐year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma

Markers of Proliferative Activity Are Predictors of Patient Outcome for Low-Grade Endometrioid Adenocarcinoma But Not Papillary Serous Carcinoma of Endometrium

Biomarkers in endometrial cancer: Possible clinical applications (Review)

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