Prognostic relevance of estrogen receptor α, β and aromatase expression in non-small cell lung cancer

Skjefstad, Kaja; Grindstad, Thea; Rakaee, Mehrdad; Richardsen, Elin; Dønnem, Tom; Kilvaer, Thomas K.; Andersen, Sigve; Bremnes, Roy M.; Busund, Lill-Tove; Al-Saad, Samer

doi:10.1016/j.steroids.2016.05.008

Cited by 44 publications

(31 citation statements)

References 34 publications

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“…The expressions of ERα and ERβ as a prognosticator for NSCLC have been reported in several studies [ 20 , 21 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ] ( Table 1 ). Contrary to that in breast cancer, ERα in lung cancer was mainly observed in the cytoplasm and associated with a poor prognosis.…”

Section: Estrogen Receptor In Lung Cancermentioning

confidence: 92%

“…Most reports found that the nuclear ERβ was predictive of a better prognosis, and the cytoplasmic ERβ was associated with a poor prognosis [ 47 , 48 ]. Nonetheless, opposing results have also been reported [ 54 , 60 , 62 , 63 , 65 , 66 ]. Co-expression of the cytoplasmic ERβ and the nuclear ERβ that had been reported correlated with a poor survival rate when compared to those without co-expression [ 67 ].…”

Section: Estrogen Receptor In Lung Cancermentioning

confidence: 98%

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Estrogen, Estrogen Receptor and Lung Cancer

Hsu

Chu

Kao

2017

IJMS

172

124

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Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER) in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR), and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

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Section: Estrogen Receptor In Lung Cancermentioning

confidence: 92%

Section: Estrogen Receptor In Lung Cancermentioning

confidence: 98%

Estrogen, Estrogen Receptor and Lung Cancer

Hsu

Chu

Kao

2017

IJMS

172

124

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“…CYP19A1 is expressed in lung cancer and has potential therapeutic value (Niikawa et al, 2008 ; Verma et al, 2011 ; Siegfried and Stabile, 2014 ). A recent IHC study on 335 NSCLC specimens found an inverse association between CYP19A1 expression with disease specific survival (Skjefstad et al, 2016 ). Similar data, although restricted to women only, were confirmed in an independent study on 150 primary lung adenocarcinoma specimens, where CYP19A1 was found as the main driver of local estrogen supply (Tanaka et al, 2016 ).…”

Section: Intracrinology In Peripheral Tissuesmentioning

confidence: 99%

Intracrine Regulation of Estrogen and Other Sex Steroid Levels in Endometrium and Non-gynecological Tissues; Pathology, Physiology, and Drug Discovery

et al. 2018

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Our understanding of the intracrine (or local) regulation of estrogen and other steroid synthesis and degradation expanded in the last decades, also thanks to recent technological advances in chromatography mass-spectrometry. Estrogen responsive tissues and organs are not passive receivers of the pool of steroids present in the blood but they can actively modify the intra-tissue steroid concentrations. This allows fine-tuning the exposure of responsive tissues and organs to estrogens and other steroids in order to best respond to the physiological needs of each specific organ. Deviations in such intracrine control can lead to unbalanced steroid hormone exposure and disturbances. Through a systematic bibliographic search on the expression of the intracrine enzymes in various tissues, this review gives an up-to-date view of the intracrine estrogen metabolisms, and to a lesser extent that of progestogens and androgens, in the lower female genital tract, including the physiological control of endometrial functions, receptivity, menopausal status and related pathological conditions. An overview of the intracrine regulation in extra gynecological tissues such as the lungs, gastrointestinal tract, brain, colon and bone is given. Current therapeutic approaches aimed at interfering with these metabolisms and future perspectives are discussed.

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“…The activity of aromatase in LC tissues is higher than that in normal lung tissues [16]. The expression of aromatase in NSCLC is associated with estrogen production [17]. CYP19A1 polymorphisms locally raises the level of estrogen in peripheral lung tissue [18].…”

Section: Discussionmentioning

confidence: 99%

Association of CYP19A1 Polymorphism with Genetic Susceptibility to Lung Cancer in Chinese population:a case-control study

et al. 2019

Preprint

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Background Lung cancer is a kind of cancer with high morbidity and mortality related to genetic factors. Many studies have shown that CYP19A1 gene polymorphism is associated with a variety of cancers, but there are few studies on lung cancer at present. The aim of the study was to explore the correlation between CYP19A1 polymorphisms and lung cancer risk in Chinese population.Methods We enrolled 510 lung cancer patients as the case group and 504 healthy people as the control group. Five single nucleotide polymorphisms determined in CYP19A1 gene were genotyped by MassARRAY, and correlation analysis was performed by Chi square test and logistic regression model.Results The genotypes of rs4646 (OR=0.77, p=0.010), rs6493487 (OR=0.76, p=0.006) and rs17601876 (OR=0.69, p=1.15E-04) in CYP19A1 gene were linked to decreasing the risk of lung cancer, while the rs1062033 (OR=1.49, p=0.029) was linked to increasing lung cancer risk. In gender-stratified analysis, female patients with the GG genotype of the rs6493487 (OR=0.31, p=0.037) and male patients with the rs17601876 (OR=0.52, p=0.012) had lower lung cancer risk. In age-stratified analysis, for patients ≥58 years, decreased lung cancer risk was correlated with the genotypes of rs4646 (OR=0.66, p=0.021), rs6493487 (OR=0.65, p=0.021) and rs17601876 (OR=0.39, p=0.001), and increased risk was associated with the GG genotype of rs1062033 (OR=2.09, p=0.003). In pathologic type-stratified analysis, the AA genotype of rs17601876 (OR=0.41, p=0.048) was associated with decreased risk of small cell lung cancer, and the AA genotype of rs4646 (OR=0.41, p=0.027), the GA genotype of rs6493487 (OR=0.65, p=0.024) and the AA genotype of rs17601876 (OR=0.34, p=0.005) were linked to decreased risk of squamous cell carcinoma.Conclusion CYP19A1 polymorphisms are associated with lung cancer risk, especially in elderly patients and patients with pathologic types of small cell lung cancer and squamous cell carcinoma.

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Prognostic relevance of estrogen receptor α, β and aromatase expression in non-small cell lung cancer

Cited by 44 publications

References 34 publications

Estrogen, Estrogen Receptor and Lung Cancer

Estrogen, Estrogen Receptor and Lung Cancer

Intracrine Regulation of Estrogen and Other Sex Steroid Levels in Endometrium and Non-gynecological Tissues; Pathology, Physiology, and Drug Discovery

Association of CYP19A1 Polymorphism with Genetic Susceptibility to Lung Cancer in Chinese population:a case-control study

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