Diagnostic approach using the expression profiling of the P53 tumor suppressor gene and its related proteins in ovarian epithelial tumors

Abstract

The initial aim of this study was to examine the expression profiles of P53 and its upstream genes, downstream genes, and cell cycle regulators to determine whether these markers are useful for making a differential diagnosis among the benign, borderline, and malignant ovarian epithelial tumors. Between borderline and malignant tumors, the increased expression levels of P53, Bax, Cyclin E, and cyclin-dependent kinase-2 as well as the decreased expression levels of growth arrest and DNA damage (GADD45) and murine double minute-2 (MDM2) were significantly associated with malignancy (P < 0.01, each). Using the receiver operating curve (ROC), the most reliable cutoff value of the added-up staining scores of those markers was 4.5 with 79% sensitivity and 89% specificity for malignancy. Between benign and borderline tumors, the P21 and Bax expression levels were significantly higher in borderline tumors, whereas the Bcl-2 expression level was much higher in benign tumors (P < 0.01, each). Using the ROC, the cutoff value of the added-up staining scores used to discriminate between the two groups was 2.5 with 70% sensitivity and 74% specificity for borderline tumors. Thus, for the differential diagnosis between borderline and malignant tumors, the cutoff value 4.5 of the cumulative staining scores can be used. However, the cutoff value 2.5 for discrimination between benign and borderline tumors may not be useful because of its relatively low sensitivity and specificity. In addition, the P53, GADD45, Cyclin E, and MDM2 expression levels in malignant ovarian tumors might be useful for determining the histologic grade and type.

Tp53 Expression And Ki-67 Proliferation Index In Surface Epithelial Tumors Of The Ovary And Their Relationship With The Histopathological Prognostic Parameters

“…Fauvet ve arkadaş-larının çalışmalarında ise, seröz tümörlerde TP53 mutasyonu, invaziv olanlarda sık ancak "borderline" olanlarda nadir; mü-sinöz tümörlerde ise TP53 mutasyonu, hem invaziv hem de "borderline" olanlarda nadir olarak saptanmıştır (32). Küçük bir seride, TP53 mutasyonu, müsinöz "borderline" tümörlerde seröz olanlara göre daha yüksek oranda gözlenmiştir (4).…”

“…TP53 mutasyonları, over tümörlerinde de en sık saptanan genetik değişikliktir (7). Tüm over kanserlerinin, yaklaşık %50-60'ında (4,(8)(9)(10)(11); seröz over karsinomlarının ise daha fazlasında TP53 geninde mutasyon bulunduğu gösterilmiştir (12). Uzun yarı ömründen dolayı, mutant TP53 immünohistokimyasal metodlarla kolaylıkla saptanır.…”

Nuclear localization of phosphorylated ERK1 and ERK2 as markers for the progression of ovarian cancer

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14]. It is subdivided according to the pathological appearance and molecular markers to four groups: serous-adenocarcinomas comprises 80% of the cancer and the rest are mucinous carcinomas, endometrioid carcinomas and clear cell carcinomas (reviewed in refs.…”

“…It is subdivided according to the pathological appearance and molecular markers to four groups: serous-adenocarcinomas comprises 80% of the cancer and the rest are mucinous carcinomas, endometrioid carcinomas and clear cell carcinomas (reviewed in refs. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Earlier it was reported that about 12-13% of total ovarian carcinomas are mucinous carcinomas, but recently, using new molecular markers, it was considered as only 2-3% of total ovarian carcinomas (16).…”

Epiregulin as a marker for the initial steps of ovarian cancer development

“…Ovarian cancer is the most lethal gynecological cancer in women because early detection is extremely difficult (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and because it is resistant to most chemotherapic drugs (15)(16)(17). The average lifespan after detection is 40.8 months for serous cancer, 21.3 months for clear cell carcinomas, 17.6 months for mucinous carcinomas and 50.9 months for endometrioid ovarian carcinomas (11).…”