p53 Expression as a Prognostic Indicator of 5-Year Survival in Endometrial Cancer

Geisler, John P.; Geisler, Hans; Wiemann, Michael C.; Zhou, Zijie; Miller, Greg A.; Crabtree, William N.

doi:10.1006/gyno.1999.5482

Cited by 63 publications

(58 citation statements)

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“…2,3,11,20 It has been shown to be overexpressed in tumors from various anatomic locations such as cervical squamous cell carcinomas, head and neck cancers and soft tissue tumors, HIF-1a in type I and type II endometrial adenocarcinoma V Pansare et al colon cancers, etc. 5,6,8,9,14 Tumor hypoxia through activation of angiogenesis helps in tumor progression and metastasis. It makes solid tumors resistant to radiation and chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…12 Overexpression of p53 protein has been shown to be an independent poor prognostic indicator associated with 5-year survival in patients with endometrial cancer and an increased likelihood of distant failure. [12][13][14] Ki-67 is a nuclear antigen that is a marker of cellular proliferation. Antibodies directed against the DNA-binding nuclear protein, Ki-67 antigen, identify cells in most of G 1 , and all of S, G 2 and M phases of cell cycle, but not in G 0 phase.…”

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Increased expression of hypoxia-inducible factor 1α in type I and type II endometrial carcinomas

et al. 2007

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Hypoxia-inducible factor 1a (HIF-1a) is a nuclear protein that is upregulated in many tumors and triggers biologic events intimately associated with aggressive tumor behavior. The aim of this study was to analyze the expression of HIF-1a, vascular endothelial growth factor (VEGF), Ki-67 and p53 in type I and type II endometrial adenocarcinoma. In total, 149 patients diagnosed with endometrial adenocarcinoma in our institute from 1995 to 2001 were included in this study, of which 108 were type I and 41 were type II endometrial adenocarcinoma. Patient demographics, clinical and pathological data were reviewed. Tissue microarrays were prepared from the paraffin blocks and immunohistochemistry was performed for antibodies against HIF-1a, VEGF, Ki-67 and p53. High expression of HIF-1a, VEGF, Ki-67 and p53 were significantly more frequent in type II than type I endometrial adenocarcinoma (Po0.001). HIF-1a expression was highly correlated with VEGF expression in the tumor cells (P ¼ 0.001). In type I endometrial adenocarcinoma, high expression of HIF-1a showed a significant correlation with higher grade of the tumor, depth of myometrial invasion, adnexal invasion and clinical stage. A similar correlation was not observed in type II endometrial adenocarcinoma. Surgical stage was the only independent prognostic marker for survival. In conclusion, high expression of HIF-1a is more frequent in type II than in type I endometrial adenocarcinoma. In type I endometrial adenocarcinoma, HIF-1a expression correlates with morphologic features of aggressiveness. In type II endometrial adenocarcinoma, there is no correlation between HIF-1a expression and these features. Thus, HIF-1a may play an important role in endometrial adenocarcinoma progression, particularly in type I endometrial adenocarcinoma. Additional investigations of HIF-1a as a biomarker of aggressive potential and as a novel target for therapeutics in endometrial adenocarcinoma are warranted. Hypoxia-inducible factor 1 (HIF-1) is a nuclear protein that activates gene transcription specifically in response to reduced cellular oxygen concentration and therefore acts as a marker for hypoxia. It is a dimeric protein with two subunits, a and b. HIF-1a is the specific hypoxia-regulated subunit. 2 Hypoxia results in stabilization of HIF-1a, facilitating nuclear HIF-1a binding and restoration of oxygen homeostasis by inducing glycolysis and angiogenesis through upregulation of vascular endothelial growth

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Increased expression of hypoxia-inducible factor 1α in type I and type II endometrial carcinomas

et al. 2007

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“…14 A substantial number of uterine serous carcinoma patients might be understaged and undertreated if this type of staging surgery is not performed. 9,[15][16][17] Tp53 gene mutations are a common genetic event in cancers 18,19 and immunohistochemistry has been shown to be an effective means for their detection. 20,21 Most Tp53 mutations in uterine serous carcinomas are missense, which results in an altered p53 protein that can be shown by immunohistochemistry because of a prolonged half life.…”

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“…20,21 Most Tp53 mutations in uterine serous carcinomas are missense, which results in an altered p53 protein that can be shown by immunohistochemistry because of a prolonged half life. 22 Variable amounts and staining intensity (from any staining to 50%) for p53 have been interpreted as evidence of p53 overexpression in the published literature, 16,[23][24][25] but the presence of strong nuclear staining in 475% of tumor cells has been shown, more specifically, to correlate with the presence of Tp53 mutations. 26 However, complete absence of p53 by immunohistochemistry may also be indicative of Tp53 mutations, as nonsense or frameshift mutations in p53 can result in a protein that is undetectable by immunohistochemistry.…”

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confidence: 99%

“…24,[28][29][30] The data regarding the prognostic significance of p53 overexpression in endometrial carcinomas, however, is controversial. Some studies have shown p53 status to be independently predictive of clinical outcome, 16,24,25,[34][35][36][37] whereas in other studies, p53 failed to retain prognostic significance on multivariate analysis. 38,39 These studies were performed on well-defined and typical subsets of endometrial carcinomas.…”

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p53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes

et al. 2010

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The distinction between uterine serous and endometrioid carcinomas can usually be achieved by morphologic examination alone. However, there are occasional 'morphologically ambiguous endometrial carcinomas' that show overlapping serous and endometrioid features and defy histologic classification. The primary aim of this study was to assess the clinical significance of p53 overexpression using immunohistochemistry in such tumors. Related aims included (1) assessing interobserver diagnostic concordance for histologic subclassification of these tumors using a panel of pathologists with and without gynecologic pathology expertise and (2) elucidating the histologic features that correlate with p53 status. Thirty-five such cases were identified during the study period. p53 overexpression was seen in 17 of 35 cases. Tumors with p53 overexpression were associated with a significantly inferior progression-free survival and disease-specific survival compared with those that lacked p53 overexpression (3-year progression-free survival and disease-specific survival were 94 and 100% in patients with no p53 overexpression, and 52 and 54% in patients with p53 overexpression; P ¼ 0.02 and 0.003, respectively). The consensus diagnosis rendered by gynecologic pathologists was predictive of disease-specific survival (P ¼ 0.002), but not progression-free survival (P ¼ 0.11). Although the interobserver diagnostic concordance (kappa ¼ 0.70) was substantial for gynecologic pathologists, and highly associated with p53 status (77% of 'favor serous' cases showed p53 overexpression, whereas only 25% of 'favor endometrioid' cases showed p53 overexpression; P ¼ 0.005), the concordance between the consensus diagnosis of the two specialized pathologists versus each of three non-specialized pathologists was poor (kappa ¼ 0.13-0.25). The histologic feature that correlated most with p53 overexpression was the presence of diffuse high nuclear grade. p53 immunohistochemistry assays in morphologically ambiguous endometrial carcinomas are roughly as clinically informative as gynecologic pathology consultation and can be helpful for prognostic assessment and therapeutic decision making in difficult endometrial carcinomas.

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Prognostic significance of combined conventional and immunocytochemical cytology for peritoneal washings in endometrial carcinoma

Luo

Sakuragi

Shimizu

et al. 2001

Cancer

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BACKGROUND Noncancerous cells simulating adenocarcinoma cells may interfere with the analysis of peritoneal cytology (PC) in patients with endometrial carcinoma. Immunocytochemistry (ICC) may improve the diagnosis of PC. METHODS PC slides from 115 patients with endometrial carcinoma were reviewed. Suspicious or positive cell clusters were recovered with a cell transfer method and were subjected to ICC for MOC‐31, cytokeratin 5/6, and p53. Conventional Papanicolaou staining and ICC results were compared directly on the same cells. RESULTS By combined conventional and immunocytochemical PC (CONV‐ICC‐PC), cytodiagnosis was positive in 18 of 115 patients (15.7%) and suspicious in 3 of 115 patients (2.6%). According to a multivariate Cox regression analysis of patients with tumors confined to the uterus that included grade, myometrial invasion, cervical involvement, and CONV‐ICC‐PC, only CONV‐ICC‐PC was an independent prognostic factor (P < 0.05). A multivariate analysis for all of the patients studied that compared CONV‐ICC‐PC with staging variables revealed that only peritoneal metastasis (P < 0.0001) and lymph node metastasis (P < 0.01) were independent prognostic factors. When peritoneal metastases were excluded, CONV‐ICC‐PC (P < 0.01) and lymph node metastasis (P < 0.0025) were the independent prognostic factors. By cell transfer and p53 immunostaining in samples from 14 patients with malignant cells in their peritoneal washings, no deaths occurred among 5 patients with negative p53, whereas 5 of 9 patients with positive p53 died of disease at the time of data analysis. CONCLUSIONS MOC‐31 immunostaining improves the diagnosis of PC in endometrial carcinoma. Positive PC is an important prognostic factor for patients with endometrial carcinoma confined to the uterus. The p53 positive cells in PC have possible prognostic significance. Cancer (Cancer Cytopathol) 2001;93:115–123. © 2001 American Cancer Society.

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p53 Expression as a Prognostic Indicator of 5-Year Survival in Endometrial Cancer

Cited by 63 publications

References 10 publications

Increased expression of hypoxia-inducible factor 1α in type I and type II endometrial carcinomas

Increased expression of hypoxia-inducible factor 1α in type I and type II endometrial carcinomas

p53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes

Prognostic significance of combined conventional and immunocytochemical cytology for peritoneal washings in endometrial carcinoma

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