An immunohistochemical analysis of sex-steroid receptors, tumor suppressor gene p53 and Ki-67 in the normal and neoplastic uterine cervix squamous epithelium

Nikolaou, Marinos; Koumoundourou, Dimitra; Ravazoula, Panagiota; Papadopoulou, Margarita; Michail, Georgios; Decavalas, George

doi:10.2298/mpns1408202n

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…ER-a and PR have previously been identified as prognostic markers in assessing breast cancer in humans with loss of expression of ER-a and/or PR indicating poor prognosis [22,23]. In human cervical cancer, a study had similar results to those in sea lions with loss of ER expression but increased PR expression in IEN [24]. Studies in other animals have identified similar associations.…”

Section: Aetiology Of Urogenital Carcinoma In the California Sea Lionmentioning

confidence: 71%

Common cancer in a wild animal: the California sea lion ( Zalophus californianus ) as an emerging model for carcinogenesis

Browning

Gulland

Hammond

et al. 2015

Phil. Trans. R. Soc. B

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Naturally occurring cancers in non-laboratory species have great potential in helping to decipher the often complex causes of neoplasia. Wild animal models could add substantially to our understanding of carcinogenesis, particularly of genetic and environmental interactions, but they are currently underutilized. Studying neoplasia in wild animals is difficult and especially challenging in marine mammals owing to their inaccessibility, lack of exposure history, and ethical, logistical and legal limits on experimentation. Despite this, California sea lions ( Zalophus californianus ) offer an opportunity to investigate risk factors for neoplasia development that have implications for terrestrial mammals and humans who share much of their environment and diet. A relatively accessible California sea lion population on the west coast of the USA has a high prevalence of urogenital carcinoma and is regularly sampled during veterinary care in wildlife rehabilitation centres. Collaborative studies have revealed that genotype, persistent organic pollutants and a herpesvirus are all associated with this cancer. This paper reviews research to date on the epidemiology and pathogenesis of urogenital carcinoma in this species, and presents the California sea lion as an important and currently underexploited wild animal model of carcinogenesis.

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Section: Aetiology Of Urogenital Carcinoma In the California Sea Lionmentioning

confidence: 71%

Common cancer in a wild animal: the California sea lion ( Zalophus californianus ) as an emerging model for carcinogenesis

Browning

Gulland

Hammond

et al. 2015

Phil. Trans. R. Soc. B

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“…Unlike epithelial ERα that diminishes during CC progression (Nonogaki et al 1990, Konishi et al 1991, Coelho et al 2004, Zhai et al 2010, Nikolaou et al 2014, den Boon et al 2015, stromal ERα continues to persist during the course of CC progression (den Boon et al 2015). Findings from both in vivo studies and experiments conducted with clinical specimens appear to be very consistent.…”

Section: Maintenance Of Erα Expression In Tumour Stromamentioning

confidence: 76%

“…Contrary to the above statement, the loss of ERα expression was established as an early alteration during the progression of cervical dysplasia to invasive carcinoma (Nonogaki et al 1990, Konishi et al 1991, Coelho et al 2004, Zhai et al 2010, López-Romero et al 2013, Nikolaou et al 2014. The majority of the basal cells in normal cervical tissue stained positive for ERα, whereas the percentage of ERα expression was decreased in CIN and squamous cervical carcinoma to 31% and 11%, respectively (Nikolaou et al 2014). In contrast, PR expression tends to increase alongside CC progression with 29% for CIN and 49% for CIN and squamous cervical carcinoma.…”

Section: Studies Using Clinical Specimens Indicate a Differential Erαmentioning

confidence: 93%

“…Experiments with clinical tissue specimens have demonstrated that ERα is intact in the normal squamous cervical epithelium. However, it appears that after successful tumour initiation, epithelial ERα is no longer a requirement, and expression is lost during the progression to CINs and invasive carcinoma, suggesting a tumour-suppressive role for epithelial ERα in cervical carcinogenesis (Zhai et al 2010, López-Romero et al 2013, Nikolaou et al 2014. Thus, only in vivo studies provide strong evidence regarding the continued expression of ERα to support the initiation and progression of CC (Chung & Lambert 2009).…”

Section: Studies Using Clinical Specimens Indicate a Differential Erαmentioning

confidence: 99%

“…ERα is expressed in the normal cervical epithelium and expression continues to decline during the various phases of CC progression (Nonogaki et al 1990, Konishi et al 1991, Coelho et al 2004, Zhai et al 2010, López-Romero et al 2013, Nikolaou et al 2014. In contrast to this trend, stromal ERα is expressed in both normal and cervical tumour tissues (Mosny et al 1989, Nonogaki et al 1990, Coelho et al 2004, López-Romero et al 2013).…”

Section: Maintenance Of Erα Expression In Tumour Stromamentioning

confidence: 99%

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Functional association of oestrogen receptors with HPV infection in cervical carcinogenesis

Ramachandran¹

2017

Endocrine-Related Cancer

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Repeated parity and usage of oral contraceptives have demonstrated an increased risk of cervical cancer (CC) in HPV-infected women. These lifestyle observations raise the likelihood that oestrogens and HPV infection might act synergistically to affect cancers of the cervix. In vivo studies have indicated the requirement of oestrogens and ERα in the development of atypical squamous metaplasia followed by cervical intraepithelial neoplasia (CIN) I, II and III. CIN II and III are precancerous cervical lesions that can progress over time to CC as an invasive carcinoma. Recently, there has been evidence suggesting that ERα signalling in the tumour epithelium is a preliminary requisite during cancer initiation that is subsequently lost during tumorigenic progression. Conversely, continued expression of stromal ERα gains control over tumour maintenance. This review summarises the current information on the association between oestrogens and HPV infection in contributing to CC and the possibility of SERMs as a therapeutic option.

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Expression of estrogen receptor alpha is associated with pathogenesis and prognosis of human papillomavirus‐positive oropharyngeal cancer

Kano

Kondo

Wakisaka

et al. 2019

Intl Journal of Cancer

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Human papillomavirus (HPV) has been identified as a causative agent of cervical cancer and oropharyngeal cancer (OPC). Intriguingly, estrogen and HPV were shown to play synergistic roles in cervical carcinogenesis. We recently demonstrated that the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which is inducible by estrogen, could lead to HPV DNA hypermutation and cause viral DNA integration. In the present study, we examined the relationships between estrogen-estrogen receptor α (ERα) and A3s in HPV-positive OPC. ERα expression was associated with HPV positivity in OPC biopsy samples using immunohistochemical analysis and reverse-transcription quantitative polymerase chain reaction. In addition, ERα was significantly associated with improved overall survival in HPV-positive OPC (hazard ratio, 0.26; p = 0.029). APOBEC3A (A3A) mRNA was induced by estrogen in HPV and ERα-positive OPC cells. Furthermore, A3A mRNA and protein expression were significantly higher in ERα-positive cases than in ERα-negative ones, among HPV-positive biopsy samples (p = 0.037 and 0.047). These findings suggest that A3A is associated with a good prognosis in ERα-positive OPC, and indicate the prognostic significance of ERα in HPV-positive OPC. This is the first study to demonstrate the prognostic role of ERα in HPVpositive OPC.The two major carcinogenic causes of oropharyngeal cancer (OPC) are human papillomavirus (HPV) infection and exposure to tobacco and alcohol, which are defined as HPV-positive and HPV-negative OPCs, respectively. 1-3 There are many biological and clinical differences between HPV-positive and HPVnegative OPCs, including prognosis, involved subsites and degree of cellular differentiation. The incidence of HPV-positive OPC has been continuously increasing in developed countries, with 50-70% of OPCs found to be linked to HPV in the United States, Europe and Japan. 4,5 Therefore, a better understanding of the characteristics of HPV-positive OPC is needed.Cervical cancer is known for its association with HPV. Cervical epithelial cells infected by HPV undergo carcinogenic transformation through the development of cancer precursor lesions called atypical squamous metaplasia (ASM) and cervical intraepithelial neoplasia. However, only a small population of cervical epithelial cells infected by HPV can evolve into cervical cancers, 6 indicating that cervical cancer development potentially requires other contributing factors in addition to HPV. Based on the analysis of a cervical cancer model using transgenic mice expressing HPV oncogenes, estrogen was identified as one of such cofactors. 7,8 Another study reported that some cervical cancers expressed the aromatase enzyme

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An immunohistochemical analysis of sex-steroid receptors, tumor suppressor gene p53 and Ki-67 in the normal and neoplastic uterine cervix squamous epithelium

Abstract: The findings of this study suggest that tumor cervical cells evade normal growth control by sex steroid hormones while synchronously abnormal regulatory mechanisms acquire control of the cell cycle.

Cited by 10 publications

References 18 publications

Common cancer in a wild animal: the California sea lion ( Zalophus californianus ) as an emerging model for carcinogenesis

Common cancer in a wild animal: the California sea lion ( Zalophus californianus ) as an emerging model for carcinogenesis

Functional association of oestrogen receptors with HPV infection in cervical carcinogenesis

Expression of estrogen receptor alpha is associated with pathogenesis and prognosis of human papillomavirus‐positive oropharyngeal cancer

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