Distinctive p53 and mdm2 Immunohistochemical Expression Profiles Suggest Different Pathogenetic Pathways in Poorly Differentiated Endometrial Carcinoma

Soslow, Robert A.; Shen, Peter U.F.; Chung, Marilda H.; Isacson, Christina

doi:10.1097/00004347-199804000-00006

Cited by 58 publications

(24 citation statements)

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“…These tumors, now generally referred to as Type 1 endometrial carcinomas, tend to occur in nulliparous, obese, hypertensive, and/or diabetic women, frequently with ovarian hormone-producing lesions, or in women who have received exogenous estrogens, and are generally low grade and low stage, slowly progressive, and associated with a favorable prognosis. Type 2 endometrial carcinomas, on the other hand, occur in women who are not constitutionally predisposed in any known way, and usually occur on a background of nonhyperplastic, often atrophic endometrium, and these carcinomas tend to be high grade, frequently of nonendometrioid type, often present at a high clinical stage, and have a highly unfavorable prognosis (1,3,(43)(44)(45)(46)(47). These clinical and pathologic differences, as well as their implications for the pathogenesis of the two different types of carcinoma, are discussed by Sherman (1) in much greater detail.…”

Section: Endometrial Hyperplasia and Carcinoma (Sg Silverberg) 319mentioning

confidence: 99%

Problems in the Differential Diagnosis of Endometrial Hyperplasia and Carcinoma

Silverberg

2000

Modern Pathology

139

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The differential diagnosis of endometrial hyperplasia and well-differentiated endometrioid adenocarcinoma is complicated not only by the resemblance of these lesions to each other, but also by their tendency to be overdiagnosed (particularly hyperplasia) on the background of polyps, endometritis, artifacts, and even normally cycling endometrium. Atypical hyperplasia may also be overdiagnosed when epithelial metaplastic changes occur in simple or complex hyperplasia without atypia. Lowgrade adenocarcinomas are best recognized by architectural evidence of stromal invasion, usually in the form of stromal disappearance, desmoplasia, necrosis, or combinations of these findings between adjacent glands. Endometrioid adenocarcinomas are usually Type 1 cancers associated with manifestations of endogenous or exogenous hyperestrogenic stimulation and a favorable prognosis. Subtypes include adenocarcinomas with squamous differentiation and secretory, ciliated cell and villoglandular variants. Rules and pitfalls in the grading of endometrioid adenocarcinomas and the estimation and reporting of myometrial invasion are presented.KEY WORDS: Differential diagnosis, Endometrial carcinoma, Endometrial hyperplasia, Grading, Myoinvasion. Mod Pathol 2000;13(3):309 -327The purpose of this article is to review the relationships between hyperplasia and adenocarcinoma of the endometrium, with an emphasis on the differential diagnostic problems both between these two lesions and between them and other entities that enter into the differential diagnostic picture. However, differential diagnosis is not the only relationship between endometrial hyperplasia and carcinoma. During the course of this review, we briefly consider the questions of the progression of endometrial hyperplasia (and specifically its atypical variant) to carcinoma, as well as the prognostic effect of the presence of endometrial hyperplasia in cases of endometrial carcinoma, and the biologic significance of carcinoma that arises in the presence or absence of hyperplasia. The last of these topics, however, is considered in much greater detail in the article by Sherman (1) in this issue.There are four possible approaches to making the differential diagnosis between atypical endometrial hyperplasia and well-differentiated endometrioid adenocarcinoma of the endometrium. These approaches may be summarized briefly as follows:(1) adenocarcinoma in situ, (2) endometrial intraepithelial neoplasia (EIN), (3) nonhistologic techniques, and (4) so-called "routine" light microscopy.The oldest of these approaches is the first, in which it is assumed that there must be an entity, conveniently named adenocarcinoma in situ, that is intermediate between the most severe atypical hyperplasia and the earliest focal change recognizable as invasive adenocarcinoma. Probably the most effective rebuttal of this concept for diagnostic purposes was made by Professor Harold Fox, who stated, "A true adenocarcinoma in situ of the endometrium is one in which the glands have undergone neoplastic change bu...

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Section: Endometrial Hyperplasia and Carcinoma (Sg Silverberg) 319mentioning

confidence: 99%

Problems in the Differential Diagnosis of Endometrial Hyperplasia and Carcinoma

Silverberg

2000

Modern Pathology

139

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“…In endometrial cancer tissue, p53 and MDM2 levels are correlated, suggesting that p53 is inactivated by MDM2 in endometrial cancer [7,8]. Furthermore, Stewart et al sequenced the TP53 gene in a series of endometrial cancer cases overexpressing p53 and found no mutations, suggesting that overexpression was due to another source such as MDM2 abnormalities [9].…”

Section: Introductionmentioning

confidence: 99%

Association between MDM2 SNP309 polymorphism and endometrial cancer risk in Polish women

Zając¹,

Stachowiak²,

Pertyński³

et al. 2012

pjp

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The prognostic value of the MDM2 gene amplification/expression in many types of cancer remains unclear. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter the protein expression and thus, may play a role in carcinogenesis. The aim of the present study was to evaluate the association between the risk of endometrial cancer and SNP309 polymorphisms in the MDM2 gene. The genotype analysis of SNP309 MDM2 gene polymorphisms in 152 endometrial cancer patients and 100 controls of cancer-free subjects, in the Polish population, was performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP). In the presented study, an association between MDM2 SNP309 polymorphisms and the incidence of endometrial cancer was identified. Our results obtained for the SNP309 polymorphisms of the MDM2 gene indicated that both the G/G genotype and the G allele are strongly associated with endometrial cancer. We did not observe any relationship between gene polymorphism and endometrial cancer progression assessed by FIGO grade. This is the first study linking single nucleotide polymorphisms of the MDM2 gene with endometrial cancer incidence in the population of Polish women. The results support the hypothesis that the SNP309 polymorphism of the MDM2 gene may be associated with the incidence of endometrial cancer in the female population.

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“…In endometrial cancer tissue, p53 and MDM2 levels are correlated, suggesting that p53 is inactivated by MDM2 in endometrial cancer (3). Furthermore, Stewart and colleagues sequenced the TP53 gene in a series of endometrial cancer cases overexpressing p53 and found no mutations, suggesting that overexpression was due to another source such as MDM2 abnormalities (4).…”

Section: Introductionmentioning

confidence: 99%

MDM2 SNP309 Is Associated with Endometrial Cancer Risk

Terry¹,

McGrath

Lee

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Mouse double-minute 2 homologue (MDM2) is a key negative regulator of p53, a tumor suppressor gene that initiates cell cycle arrest and apoptosis in response to DNA damage and other cellular stresses. A T > G polymorphism found in the promoter region of MDM2 (SNP309) increases MDM2 expression and thereby attenuates p53 activity. We genotyped the MDM2 polymorphism SNP309 in endometrial cancer casecontrol studies nested within the Nurses' Health Study (454 cases and 1,132 controls) and the Women's Health Study (137 cases and 411 controls). Due to a significant difference in genotype distribution by ethnicity, we restricted our analyses to Caucasians. We calculated odds ratios and 95% confidence intervals using conditional and unconditional logistic regression adjusted for age at menarche, parity and age at first birth, postmenopausal hormone use at diagnosis, age at menopause and menopausal status at diagnosis, first-degree family history of colon cancer, body mass index at diagnosis, and cigarette smoking status at diagnosis. Women with a heterozygous genotype had no greater risk whereas those with a homozygous variant genotype had a greater risk than women with a wild-type genotype for the MDM2 SNP309 (covariate-adjusted odds ratio, 1.87; 95% confidence interval, 1.29-2.73) for endometrial cancer. We observed no association between age at diagnosis and genotype. Women carrying two copies of the MDM2 SNP309 variant may be at greater risk of endometrial cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(4):983 -6)

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Distinctive p53 and mdm2 Immunohistochemical Expression Profiles Suggest Different Pathogenetic Pathways in Poorly Differentiated Endometrial Carcinoma

Cited by 58 publications

References 0 publications

Problems in the Differential Diagnosis of Endometrial Hyperplasia and Carcinoma

Problems in the Differential Diagnosis of Endometrial Hyperplasia and Carcinoma

Association between MDM2 SNP309 polymorphism and endometrial cancer risk in Polish women

MDM2 SNP309 Is Associated with Endometrial Cancer Risk

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