Prognostic significance of steroid receptors measured in primary metastatic and recurrent endometrial carcinoma

Borazjani, Gholamreza; Twiggs, Leo B.; Leung, Benjamin S.; Prem, Konald A.; Adcock, Leon L.; Carson, Linda F.

doi:10.1016/0002-9378(89)90677-7

Cited by 17 publications

(4 citation statements)

References 15 publications

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“…In endometrial cancer, receptors to many steroid hormones, including androgens and glucocorticoids, have been detected 46,47 . The estrogen receptors are invariably found in this cancer, which, at least temporarily, is totally dependent on estradiol.…”

Section: Er and Pr Concentrations In Different Physiological And Pathmentioning

confidence: 99%

Estrogen and Progesterone Receptors in the Endometrium

Moutsatsou

Sékeris

1997

Annals of the New York Academy of Sciences

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The endometrium, as a target of estrogens and progestins, possesses the respective receptor proteins. These receptors belong to the superfamily of nuclear receptors, having important functional domains required for steroid ligand binding, for dimer formation, for interaction with HREs of DNA, for transcription modulation, for association with other proteins, for intracellular trafficking, and other activities. The mechanism of action of the steroid hormones involves modulation of gene activity through interaction of the hormone-receptor complex with HREs and with other nuclear proteins, but also encompasses nongenomic effects, which accounts for the rapid effects of the steroids on cellular functions. Antihormones-antiestrogen and antiprogestins-compete with their respective hormones for binding sites on the receptor molecules. Some antihormones are partial agonists. The molecular mechanisms underlying the dual behavior of antihormones is under consideration. The concentration of ER and PR in different physiological and pathophysiological states, such as the menstrual cycle, pregnancy, and endometrial cancer, has been determined by biochemical and immuno(cyto)chemical methods. The levels of estrogens and progestins are important regulators of ER and PR gene expression. Estradiol acts as a cell mitogen, inducing key genes involved in replication, and its tumor promoter effect is discussed in this sense, whereas progesterone has reverse effects when compared to estradiol and acts as a differentiation factor. The cross-talk between the endocrine system, growth factors, and neurotransmitters can take place both at the receptor level, involving mainly phosphorylation reactions, and at the gene level, mainly through protein-protein interactions.

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Section: Er and Pr Concentrations In Different Physiological And Pathmentioning

confidence: 99%

Estrogen and Progesterone Receptors in the Endometrium

Moutsatsou

Sékeris

1997

Annals of the New York Academy of Sciences

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“…The three major criteria for therapeutic decisions include myometrial invasion, tumor grading, and extrauterine tumor spread [3,4]. The search for prognostic and/or predictive factors in endometrial cancer include DNA ploidy and S-phase [5,6], expression of the steroid hormone receptors [7][8][9], the epidermal growth factor receptor, the Her-2/neu protein, and the p53 protein [10][11][12][13][14][15]. In these studies tumors with high FIGO classification showed decreased estrogen (ER) and progesterone receptor (PgR) expression [7,8] and increased epidermal growth factor receptor, Her-2/neu, and p53 expression [6,[11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Mutations and Amplification of Oncogenes in Endometrial Cancer

Niederacher

An²,

Cho

et al. 1999

Oncology

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Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer.

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“…In endometrial adenocarcinomas high levels of estrogen and progesteronereceptors are usually found only in well‐differentiated endometrioidadenocarcinomas, while these receptors are either absent or onlyexpressed at a low level in poorly‐differentiatedneoplasms(59,63,64). The receptor status of endometrialneoplasms is widely thought tobe an important prognostic factor, the presence of receptors in high contentbeing indicative of a good clinical outcome(65–71). Nevertheless, the independent prognostic significance of estrogenreceptor positivity has, with only rare exceptions(72), not withstood the test of multivariate analysis, though a high progesteronereceptorcontent of a neoplasm does appear to be an independent prognostic variableindicative of a good prognosis(73).…”

Section: Steroid Hormone Receptorsmentioning

confidence: 99%