The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma

Shahin, Mark S.; Hughes, Jonathon H.; Sood, Anil K.; Buller, Richard E.

doi:10.1002/1097-0142(20001101)89:9<2006::aid-cncr18>3.0.co;2-7

Cited by 48 publications

(12 citation statements)

References 37 publications

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“…In line with previous studies, advanced FIGO stage and residual tumour after surgery were significantly associated with poor prognosis, both in terms of OS, DSS and PFS, and remained independent prognosticators in multivariate analysis (3)(4)(5)(27)(28)(29)(30)(31)(32)(33)(34)(35). Advanced age at diagnosis contributed independently to DSS but not to OS, in agreement or in contrast with the findings of other studies (5, 12, 18, 27-32, 34, 35).…”

Section: Discussionsupporting

confidence: 89%

Association of CD31 and p53 With Survival of Ovarian Cancer Patients

et al. 2019

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Background/Aim: New markers for ovarian cancer are needed. This study aimed to examine the expression of tumour cell p53 and endothelial cell CD31 proteins and correlate them to clinicopathological factors. Patients and Methods: Expression of proteins was immunohistochemically assessed using tissue sections from 585-599 ovarian cancer patients from the Danish MALOVA study. Results: High CD31 expression was found in poorly differentiated tumours (p=0.0006), and high p53 expression was found in poorly differentiated cancers (p<0.0001), high clinical stage (p<0.0001), non-radical surgery (p<0.0001) and high serum . CD31 expression showed no prognostic survival value, but high hazard ratios were found for patients with high p53 expression (HR=2.313, p<0.0001). An interaction was found between p53 and stage of cancer, suggesting a prognostic impact of p53 in low-stage, but not in advancedstage cancer. Conclusion: More than 5% of p53 tissue expression may predict shorter survival of ovarian cancer patients and may be useful for predicting the risk of disease progression in low-stage patients following primary surgery. CD31 has no strong prognostic value.Cancer of the ovaries is the ninth most frequently diagnosed cancer in women (1). Due to the lack of symptoms, most patients are diagnosed at a late clinical stage, efficaciously reducing survival. Six-year survival rate of Danish ovarian and peritoneal cancer patients (years 2005-2011) ranged from 80% for stage I patients to 10.8 % for stage IV patients (www.dgcg.dk). Therefore, biomarkers of molecular changes specific for ovarian cancer (OC) development and progression are required in order to stratify patients to risk groups.OCs vary in clinical behaviour and are classified into histological subtypes (serous, mucinous, endometrioid and clear cell) (2). Negative prognostic indicators for OC include advanced FIGO stage, high tumour grade, incomplete surgical tumour resection and mutations in proto-oncogenes Kirsten rat sarcoma virus (KRAS), V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) and tumour suppressor p53 (TP53) (3-6). Other suggested prognostic indicators are markers for angiogenesis (7).Synthesis and rearrangement of blood vessels are necessary during massive tumour growth, where the cells depend on oxygen and nutrients as well as discharge of waste substances by the blood stream, and the majority of tissue cells are found within 100 μm from blood supply (8). Angiogenesis in tumour growth can be studied using immunohistochemistry, which can detect endothelial cellspecific proteins, such as platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) (9).CD31 protein is present on endothelial cells in intratumoural microvessels of cancers such as OC (10). In OC, conflicting results have been obtained regarding the correlation of high CD31 expression with advanced disease and poor survival (11)(12)(13)(14)(15)(16)(17)(18).An important gene involved in cell-cycle regulation, DNA repair and apoptosis is the TP53 gene located on chromosome 17 and encoding th...

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Section: Discussionsupporting

confidence: 89%

Association of CD31 and p53 With Survival of Ovarian Cancer Patients

et al. 2019

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“…Null mutation (insertion, deletion, splice site aberration, and nonsense) result in a truncated protein product that cannot bind DNA or induce apoptosis. Such mutation generally do not result in increased p53 stability, and the truncated protein is often undetected by conventional immunohistochemical techniques (40).…”

Section: Markers Of Apoptosismentioning

confidence: 99%

“…Several lines of evidence have elucidated a major role of functional p53 gene for enhancing therapeutic response to chemotherapy or radiation. Mutant p53 therefore may directly decrease tumor cell sensitivity to chemotherapeutic agents and promote the emergence of drug resistant population of cancer cells (38,40).…”

Section: Markers Of Apoptosismentioning

confidence: 99%

“…The role of p53 protein in EOC is contentious, and there is a number of studies with contradictory results. Several studies have identified p53 protein as an adverse prognostic factor for survival in EOC (18,31,33,40). Other studies have suggested that alterations in p53 expression in ovarian cancer affect sensitivity to chemotherapy (35,38).…”

Section: Markers Of Apoptosismentioning

confidence: 99%

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Contribution of Immunohistochemistry in Prognostic Assessment of Epithelial Ovarian Carcinoma – Review of the Literature I.

Tomšová

Melichar²

2006

Acta Med. (Hradec Kralove, Czech Repub.)

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Epithelial ovarian carcinoma is worldwide the sixth most common female cancer, and this malignancy carries the highest mortality among all gynecological cancers. The high mortality is due mostly to the fact that the tumor is frequently diagnosed late, in advanced stage, as the early disease is often asymptomatic and no effective screening methods are available. The most important prognostic factors in ovarian carcinoma are the stage, size of residual tumor following surgery, presence of ascites, age and the general condition of the patient, tumor histology, and, in patients with early disease, also the grade of the tumor. Large number of studies on prognostic and predictive factors in epithelial ovarian carcinoma has been published, often with contradictory results. The most intensely studied prognostic factors are those for expression of hormonal receptors, for tumor proliferation activity (mainly by antigen Ki-67 and topoisomerase IIα), the markers of apoptosis (p53, p21, mdm2, bcl-2 and other proteins), or other oncoproteins (particularly HER-2/neu).

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“…Diffuse (≥75%) and strong nuclear p53 expression is typically regarded as a missense mutation of TP53, and a complete lack of p53 immunoreactivity is attributed to nonsense or frameshift mutation, which leads to the formation of a truncated, nonimmunoreactive protein. 4,[6][7][8][9] Aberrant p53 expression (ie, either uniform and strong or completely absent expression) indicates mutant p53, while expression levels between these 2 extremes represent wild-type p53.…”

Section: Introductionmentioning

confidence: 99%

Cardiophrenic Lymph Node Metastasis of Ovarian High-grade Serous Carcinoma Showing Wild-type p53 Immunostaining Pattern and Aberrant CD56 Expression

Kwon

Han

et al. 2021

Int J Surg Pathol

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Patterns of p53 immunostaining are used as a surrogate marker for tumor protein 53 ( TP53) mutations in the diagnosis of ovarian high-grade serous carcinoma (HGSC). We present a rare case of ovarian HGSC that metastasized to the diaphragm and cardiophrenic lymph nodes and showed the immunostaining pattern of wild-type p53 and aberrant neural cell adhesion molecule (CD56) expression. A 63-year-old woman developed multifocal metastases in the diaphragmatic pleura and cardiophrenic lymph nodes. Because she had a history of ovarian HGSC and pulmonary adenocarcinoma, we considered the possibility that the metastatic carcinoma was of either ovarian or pulmonary origin. Immunostaining revealed that the tumor cells were negative for thyroid transcription factor 1 but positive for Wilms tumor 1. The tumor additionally exhibited strong membranous CD56 expression and patchy p53 expression, both of which were inconsistent with the characteristics of ovarian HGSC. However, targeted sequencing analysis revealed that the tumor harbored a pathogenic mutation at the splice acceptor site of TP53 intron 9 (c.994-1G>C).

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The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma

Abstract: The authors thank Charles S. Davis, Ph.D. for statistical assistance, and Colleen Fullenkamp, William Page, and Marisa Dolan for technical assistance. Barrie Anderson, M.D. and Joel I. Sorosky, M.D. provided tissue samples from their patients for the Iowa ovarian cancer tissue bank.

Cited by 48 publications

References 37 publications

Association of CD31 and p53 With Survival of Ovarian Cancer Patients

Association of CD31 and p53 With Survival of Ovarian Cancer Patients

Contribution of Immunohistochemistry in Prognostic Assessment of Epithelial Ovarian Carcinoma – Review of the Literature I.

Cardiophrenic Lymph Node Metastasis of Ovarian High-grade Serous Carcinoma Showing Wild-type p53 Immunostaining Pattern and Aberrant CD56 Expression

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