Analysis of sex-hormone-receptor expression in laryngeal carcinoma

Hagedorn, Hjalmar; Nerlich, Andreas G.

doi:10.1007/s004050100400

Cited by 24 publications

(20 citation statements)

References 22 publications

(56 reference statements)

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“…Estrogen receptors function as transcription factors and play a role in the progression of several human malignancies. Although the expression of steroid receptors was controversial in laryngeal carcinoma (27), our results confirmed recent data showing ER-ß expression in laryngeal cancer (28). Table I.…”

Section: Discussionsupporting

confidence: 91%

Estrogen receptor-β expression in human laryngeal carcinoma: correlation with the expression of epithelial-mesenchymal transition specific biomarkers

Goulioumis

Fuxe²,

Varakis³

et al. 2009

Oncol Rep

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Abstract. Laryngeal carcinoma is a malignancy of the respiratory tract with a significantly higher male to female ratio, suggesting involvement of gender-depended factors in the pathogenesis. Estrogen influences the pathological processes of hormone-dependent cancers, such as breast, prostate and ovarian cancers, through its receptors, estrogen receptor-· (ER-·) and -ß (ER-ß). While ER-· promotes cell proliferation, recent studies indicate that ER-ß is protective against carcinoma progression into an invasive state. However, it is unclear whether ER-ß plays a role in laryngeal cancer. In the present study we examined the expression of ER-ß in 80 invasive human squamous laryngeal carcinomas by immunohistochemistry and correlated ER-ß expression with markers of epithelial-mesenchymal transition (EMT). ER-ß was expressed in 83% of tumour specimens where it was localized in the nuclei of tumour cells. The expression of ER-ß correlated positively with the maintenance of Ecadherin and ß-catenin at cell junctions and negatively with the loss of E-cadherin, nuclear translocation of ß-catenin and increased TNM stage. We concluded that estrogen receptor-ß expression is documented in laryngeal cancer indicating a possible role in the pathogenesis of this malignancy. It is suggested that ER-ß could protect tumour cells from acquiring aggressive EMT features such as E-cadherin downregulation and nuclear ß-catenin activation.

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Section: Discussionsupporting

confidence: 91%

Estrogen receptor-β expression in human laryngeal carcinoma: correlation with the expression of epithelial-mesenchymal transition specific biomarkers

Goulioumis

Fuxe²,

Varakis³

et al. 2009

Oncol Rep

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“…Previous studies have demonstrated that 23–79% of laryngeal cancer cases express ERs (16–18,24), concluding that positive ER expression is gender independent with a positive prognostic influence on survival. However, other authors have not been able to identify ER expression in laryngeal cancer (25,26), therefore laryngeal carcinogenesis may be a hormonally independant process. Non-identification of ER in epithelial components of the normal larynges and laryngeal carcinomas has been confirmed (27).…”

Section: Discussionmentioning

confidence: 96%

The prognostic significance of estrogen receptor β in head and neck squamous cell carcinoma

et al. 2016

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Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world. Although multimodal and targeted therapy is now used in therapeutic procedures, the survival of patients with HNSCC has remained unchanged over the last 30 years. A number of studies have demonstrated that the increased expression of intranuclear ERβ in breast, lung and colon cancer is a favorable prognostic marker associated with higher survival rates. However, the clinical significance of sex hormone receptors in HNSCC remains unclear. The current study aimed to assess the expression of ERβ in HNSCC immunohistochemically and investigate any possible association between ERβ expression, and clinical and histopathological factors, disease recurrence and patient survival. The present study included 174 patients (165 males and 9 females) with a median age of 60.8 years (range, 39–79) with HNSCC who were primary surgically treated between January 2000 and December 2006. Immunohistochemical reactions for ERβ demonstrated that 73 patients (42%) exhibited positive ERβ expression. Distribution of ERβ status among different head and neck subsites indicated that >40% of all negative cases were located in laryngeal primaries, while incidence of other sublocalization within positive cases was similar and comparable (P=0.04). Furthermore, a correlation was observed between ERβ immunopositivity and the survival of patients, with respect to the primary tumor site. Patients with ERβ positive oropharyngeal cancer had a survival rate of 35.3% at 5-years compared with 25% for patients with negative expression. However, ERβ status was not significantly correlated with any other clinical or histopathological parameter. After an average follow-up time of 38.5 months (range, 3–60 months), 54 patients (31.1%) had succumbed to disease recurrence while 50 (28.7%) succumbed to other causes. In conclusion, ERβ positivity indicates improved survival of patients with oropharyngeal cancer. Further research is required in order to implement novel therapeutic strategies.

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“…The presence of classical cytosolic ERs is controversial in laryngeal cancer [22, 13]. Despite this, laryngeal cancer cells display E 2 responsiveness, as E 2 was found to increase proliferation of laryngeal cancer cells [8], and a non-genomic mechanism was implicated [24].…”

Section: Introductionmentioning

confidence: 99%

17Beta-Estradiol Promotes Aggressive Laryngeal Cancer Through Membrane-Associated Estrogen Receptor-Alpha 36

et al. 2013

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17β-estradiol (E2) plays a key role in tumorigenesis by enhancing cell survivability and metastasis through its cytoplasmic receptors. Recently, a variant of estrogen receptor alpha, ERα36 has been implicated as a substantial mediator of E2’s proliferative and anti-apoptotic effects through rapid membrane-associated signaling, and cancers previously regarded as hormone-independent due to the absence of traditional receptors, may in fact be susceptible to E2. Despite rising from a secondary sex organ and having a clear gender disposition, laryngeal cancer is not uniformly accepted as hormone-dependent, even in the face of compelling evidence of E2 responsiveness. The aim of this study was to further elucidate the role of E2 in the tumorigenesis of laryngeal cancer, both in vitro and in vivo. ERα36 presence was evaluated in membranes of the laryngeal carcinoma cell line, Hep2, as well as in laryngeal tumor samples. In vitro, ERα36 was found to mediate rapid activation of protein kinase C and phospholipase D by E2, leading to increased proliferation and protection against chemotherapy-induced apoptosis. Furthermore, in response to E2 activation of ERα36, an upregulation of angiogenic and metastatic factors was observed. Clinical analysis of laryngeal tumors revealed a similar association between the amount of ERα36 and VEGF, and indicated a role in lymph node metastasis. These findings present compelling evidence of ERα36-dependent E2 signaling in laryngeal cancer. Thus, targeting ERα36 may reduce the deleterious effects of E2 in laryngeal cancer, ultimately suggesting the importance of anti-estrogen therapy or the production of novel drugs that specifically target ERα36.

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Analysis of sex-hormone-receptor expression in laryngeal carcinoma

Cited by 24 publications

References 22 publications

Estrogen receptor-β expression in human laryngeal carcinoma: correlation with the expression of epithelial-mesenchymal transition specific biomarkers

Estrogen receptor-β expression in human laryngeal carcinoma: correlation with the expression of epithelial-mesenchymal transition specific biomarkers

The prognostic significance of estrogen receptor β in head and neck squamous cell carcinoma

17Beta-Estradiol Promotes Aggressive Laryngeal Cancer Through Membrane-Associated Estrogen Receptor-Alpha 36

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