p53 and mdm2 as prognostic indicators in patients with epithelial ovarian cancer: A multivariate analysis

Dogan, Erbil; Saygılı, Uğur; Tuna, Burçin; Göl, M. Kamii; Gürel, Duygu; Acar, Berrin; Koyuncuoğlu, Meral

doi:10.1016/j.ygyno.2004.12.053

Cited by 35 publications

(36 citation statements)

References 30 publications

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“…Again, the prognostic value of MDM2 expression in ovarian cancer is controversial. Two studies found no prognostic relevance of MDM2 expression in ovarian cancer (29,30), whereas Dogan et al reported a significantly impaired overall survival in MDM2 positive as compared to MDM2 negative ovarian carcinomas (31).…”

Section: Discussionmentioning

confidence: 97%

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

Hofstetter

Berger²,

Bauer³

et al. 2011

Oncol Rep

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Abstract.A single nucleotide polymorphism (SNP309) of MDM2 causes elevated MDM2 levels and an attenuation of p53 function. The aim of the present study was to examine the clinical relevance of the MDM2 SNP309 in ovarian cancer. MDM2 SNP309 genotype was analyzed in 198 patients with primary ovarian cancer. MDM2 expression was investigated using immunohistochemistry. A functional yeast-based assay and subsequent sequencing were performed to determine p53 mutational status. Of the patients, 44.4% (88 of 198) exhibited the common variant (T/T), 40.9%

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Section: Discussionmentioning

confidence: 97%

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

Hofstetter

Berger²,

Bauer³

et al. 2011

Oncol Rep

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“…Aynı konuda, Türkiye'den yapılmış çalışmalarda da, %41.6 ile %72.5 arasında değişen oranlarda TP53 ekspresyonu bildirilmiştir (31,(33)(34)(35)(36)(37)(38).…”

Section: Overin Yüzey Epitelinde Tp53 Ekspresyonuunclassified

“…Milner ve arkadaşlarının çalışmalarında da, yüksek dereceli seröz karsinomlarda, endometrioid ve müsinöz karsinomlara göre daha sık TP53 mutasyonları saptanmıştır (9). Yine, ülkemizden Doğan ve arkadaşlarının çalışmalarında da (n=82), TP53 ekspresyonunun, seröz subtip ile ilişkili olduğu gösterilmiştir (33). Çalışmamızda da, seröz karsinomların %42.9'unda, tümör hüc-relerinin %80'inden fazlasında TP53 ekspresyonu görülürken; bu oran, non-seröz karsinomlarda %15.9 idi.…”

Section: Overin Yüzey Epitelinde Tp53 Ekspresyonuunclassified

“…Ülkemizden, Doğan ve arkadaşlarının çalışmalarında (n=82) da, TP53 ekspresyonunun, seröz subtip, yüksek derece ve pozitif peritoneal sitopatolojiye ek olarak, rezidü tümör, ileri evre ve kötü sağkalım ile de ilişkili olduğu gösterilmiştir (33). Yine Özalp ve arkadaşlarının çalışmalarında da, over karsinomlarında (n=26) TP53 aşırı-ekspresyonu, yüksek derece, ileri evre ve kısa ortalama sağkalım süresi ile ilişkili bulunmuştur (34, 35).…”

Section: Overin Yüzey Epitelinde Tp53 Ekspresyonuunclassified

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

Özkara¹,

Filinte²

2010

TUTFD

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ÖZETAmaç: Malign, "borderline" ve benign epitelyal over tümörlerinde TP53 ve Ki-67 ekspresyonlarını; karsinomlarda histopatolojik parametrelerle iliş-kisini; farklı özelliklerdeki olgu gruplarında TP53 ve Ki-67 ekspresyonlarını araştırmak; overde karsinogenezi tartışmak. Gereç ve Yöntemler:Yüz'ü malign, 27'si "borderline" ve 31'i benign, toplam 158 epitelyal over tümörü ve 42 non-tümöral over dokusunda standart immunohistokimya tekniği kullanıldı.Bulgular: TP53 aşırı-ekspresyonu, "borderline" tümörlere (%40.7) kıyasla malignlerde (%61.0); 50 yaş üstündeki; yüksek dereceli, az/indiferansiye ve seröz; solid yapılanmalı seröz, yüksek pleomorfizm dereceli seröz ve non-seröz, yüksek mitotik indeksli non-seröz subtiplerde; lenf nodu tutulumu gösteren, ileri evredeki karsinomlarda daha yüksekti (p<0.05). Ortalama Ki-67 indeksleri, malignlerde %41.3, "borderline" tümörlerde %17.2 olup; fark anlamlıydı. Karsinomların Ki-67 indeksleri, dereceleri yükseldik-çe artarken; lenf nodu tutulumlu olgularda azalma gösterdi. Karsinomların farklı subtiplerinin, derecelerine, lenf nodu tutulumları ve evrelerine göre, TP53 ekspresyonları ve Ki-67 indeksleriyle ilişkilerinde farklılıklar saptandı.Sonuç: TP53 aşırı-ekspresyonunun, malign ve "borderline" over tümör-lerinin gelişimindeki rolünü desteklemektedir. Karsinomlarda, TP53 ekspresyonunun derecesi, yaş, histopatolojik subtip, derece, pleomorfizm, yapılanma özelliği, mitotik aktivite, lenf nodu tutulumu ve evre ile ilişkili olarak farklılık; Ki-67 proliferasyon indeksi ile de korelasyon göstermekte-dir. Malign epitelyal over tümörlerinin bu biyolojik parametrelere göre de ayrılması, gelecekte daha olguya özgün tedavi protokollerinin belirlenmesinde, özellikle erken evrede önemli olabilir. Material and Methods: Standard immunohistochemistry was performed in 100 malignant, 27 borderline and 31 benign tumors and 42 non-tumoral ovarian epithelia.Results: TP53 overexpression was higher in malignant (61.0%) than in borderline tumors (40.7%); in malignant cases above 50 years-of-age, with high grade and in undifferentiated and serous subtypes. Carcinomas with solid architecture in serous, high mitosis in non-serous and high pleomorphism in both subtypes; lymph node involvement, and advanced stage also showed higher expressions of TP53 (p<0.05). The mean Ki-67 index was 41.3% in malignant and 17.2% in borderline tumors. Ki-67 index tended to increase with increasing grade, and decrease with lymph node involvement. The coexpression of proteins according to grade, lymph node involvement and stage in different subtypes, showed significant differences and correlations.Conclusion: Our findings support the role of TP53 overexpression in development of "borderline" and malignant epithelial ovarian tumors. The degree of TP53 expression differed in terms of histopathological parameters; and was correlated with Ki-67 index. Especially in early stages, these biological factors could provide additional information to stratify patients for case specific therapies.

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“…Grade not determined (64%) 33/46 (72) (Gadducci et al, 2006) 47/71 (66) (Havrilesky et al, 2003) 16/26 (62) (Caduff et al, 1999) 14/31 (45) (Fujita et al, 1994) 11/20 (55) (Henriksen et al, 1994) 18/23 (78) (Renninson et al, 1994) 31/42 (74) (Dogan et al, 2005) 73/126 (58) (Eltabbakh et al, 1997) Clear cell (8%) 6/38 (17) (Ho et al, 2001) 0/4 (0) (Otis et al, 2000) 1/12 (8) (Caduff et al, 1999) Endometrioid (45%) 5/15 (33) (Dogan et al, 2005) 7/13 (54) (Henriksen et al, 1994) 13/27 (48) (Caduff et al, 1999) Mucinous (19%) 1/12 (8) (Dogan et al, 2005) 3/12 (25) (Renninson et al, 1994) 3/11 (27) (Henriksen et al, 1994) 3/21 (14) (Caduff et al, 1999) (Hashiguchi et al, 2001) 70/117 (60) (Saegusa et al, 2001) 28/82 (34) (Havrilesky et al, 2001) 9/73 (12) (Tachibana et al, 2003) 23/107 (21) (Hashiguchi et al, 2001) 60/134 (45) (Bali et al, 2004) RB Homozygous mutation (9%) 1/24 (4) (Sasano et al, 1990) 2/15 (13) Loss of or aberrant expression (19%) 2/25 (8) (Dodson et al, 1994) 2/26 (8) (Kim et al, 1994) 3/22 (14) (Taylor et al, 1995) 7/34 (21) (Niemann et al, 1998) 2/59 (3) (Kusume et al, 1999) 5/46 (11) (Hashiguchi et al, 2001) 7/9 (78) (Gras et al, 2001) 10/84 (12) (Havrilesky et al, 2001) 1/78 (1) (Konstantinidou et al, 2003) 28/134 (21) (Bali et al, 2004) 12/107 (37) (Hashiguchi et al, 2...…”

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confidence: 99%

Role of p53 and Rb in Ovarian Cancer

Corney

Flesken‐Nikitin

Choi

et al.

Advances in Experimental Medicine and Biology

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Ovarian cancer remains a major health concern worldwide, primarily in postmenopausal women. Among the most common genetic alterations in human sporadic epithelial ovarian cancer (EOC) are p53 mutations, defective retinoblastoma (RB) pathway (p16 INK4a /RB) and activation of oncogenes such as c-myc, K-ras and Akt. Although these alterations are frequently associated with poor clinical prognosis, their specific contributions to EOC formation remain unclear. In order to gain a better understanding of the roles of these proteins in vivo, a number of mouse models have been generated, largely based upon inducing specific genetic lesions in the ovarian surface epithelium from which the majority of carcinomas are thought to arise in humans. Here, we review the role of tumor suppressor p53 and the Rb pathway in EOC with particular attention to association of p53 to high grade serous carcinomas as opposed to low grade and benign tumors. We also provide an overview of the utility and application of genetically engineered mouse models, in particular towards rational drug design and development of improved imaging techniques in ovarian cancer.

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p53 and mdm2 as prognostic indicators in patients with epithelial ovarian cancer: A multivariate analysis

Cited by 35 publications

References 30 publications

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

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

Role of p53 and Rb in Ovarian Cancer

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