Steroid hormone receptors in carcinoma of the cervix

Hunter, Richard; Longcope, Christopher; Keough, Paul

doi:10.1002/1097-0142(19870801)60:3<392::aid-cncr2820600318>3.0.co;2-c

Cited by 35 publications

(12 citation statements)

References 15 publications

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“…Clinical evidence that estrogens and progesterone may have a carcinogenic effect in HPV‐infected cervix was recently reported in two multicentric case‐control studies ( 63,64 ) . Our ER‐ and PR‐positive results are similar to previous studies relying on ER and PR detection in cervical cancer ( 39,65–69 ) . However, wide variation exists between ER and PR reports on cervical cancer probably due to the differences in the methods employed, sample preparation, and different cut‐off values for positive results.…”

Section: Discussionsupporting

confidence: 91%

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

Fonseca-Moutinho¹,

Cruz

Carvalho

et al. 2004

Int J Gynecol Cancer

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Abstract. Fonseca-Moutinho JA, Cruz E, Carvalho L, Prazeres HJM, de Lacerda MMP, da Silva DP, Mota F, de Oliveira CF. Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III. Int J Gynecol Cancer 2004;14:911-920.There are no known biological markers or technologies to predict the natural history of an individual CIN III. The probability of progression is considered greater with the persistence of high-risk human papillomavirus (HPV) infection and age. p53 polymorphism has been associated with cervical carcinogenesis. Hormone-induced cervical cancer is mediated by estrogen receptor (ER) and progesterone receptor (PR). In cervical cancer, increased bcl-2 and Bax immunoreactivity is generally associated with a better prognosis. The purpose of this study was to evaluate the value of HPV 16 and HPV 18 typing and p53 codon polymorphism genotyping by polymerase chain reaction and ER, PR, bcl-2, and Bax expression by immunohistochemistry in predicting the CIN III clinical behavior of CIN III lesions. We studied the expression of these prognostic factors in the CIN III adjacent to squamous cell microinvasive carcinomas of the cervix (MIC) from 29 patients with FIGO stage IA1 cervical cancer and in 25 patients with CIN III and no documented focus of invasion. In the MIC group, only the CIN III was considered at least 2 mm away from the microinvasive complex. The ER, PR, bcl-2, and Bax immunoreactivity was scored as positive (>10% staining cells) and negative (<10% staining cells). No significant difference was observed between MIC and CIN III group concerning HPV infection and p53 polymorphism. The ER, PR, bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After multivariable analysis, coexpression of ER, PR, and bcl-2 was the only independent factor in defining low risk of progression for CIN III. Our study suggests that coexpression of ER, PR, and bcl-2 may be a useful tool in identifying the CIN III lesions with low risk of progression to cervical cancer.KEYWORDS: cervical microinvasive carcinoma, CIN III, immunohistochemistry, prognosis.Cervical cancer is one of the most frequent cancers in women, with an estimated worldwide incidence of about 371,000 new cases per year and an overall 5-year survival ranging from 44 to 66% for all clinical stages (1) .

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Section: Discussionsupporting

confidence: 91%

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

Fonseca-Moutinho¹,

Cruz

Carvalho

et al. 2004

Int J Gynecol Cancer

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“…Clinical evidence that estrogens and progesterone may have a carcinogenic effect in HPV-infected cervix was recently reported in two multicentric case-control studies (63,64) . Our ER-and PR-positive results are similar to previous studies relying on ER and PR detection in cervical cancer (39,(65)(66)(67)(68)(69) . However, wide variation exists between ER and PR reports on cervical cancer probably due to the differences in the methods employed, sample preparation, and different cut-off values for positive results.…”

Section: Discussionsupporting

confidence: 90%

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

Fonseca-Moutinho

Cruz

Carvalho

et al. 2004

International Journal of Gynecological Cancer

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There are no known biological markers or technologies to predict the natural history of an individual CIN III. The probability of progression is considered greater with the persistence of high-risk human papillomavirus (HPV) infection and age. p53 polymorphism has been associated with cervical carcinogenesis. Hormone-induced cervical cancer is mediated by estrogen receptor (ER) and progesterone receptor (PR). In cervical cancer, increased bcl-2 and Bax immunoreactivity is generally associated with a better prognosis. The purpose of this study was to evaluate the value of HPV 16 and HPV 18 typing and p53 codon polymorphism genotyping by polymerase chain reaction and ER, PR, bcl-2, and Bax expression by immunohistochemistry in predicting the CIN III clinical behavior of CIN III lesions. We studied the expression of these prognostic factors in the CIN III adjacent to squamous cell microinvasive carcinomas of the cervix (MIC) from 29 patients with FIGO stage IA1 cervical cancer and in 25 patients with CIN III and no documented focus of invasion. In the MIC group, only the CIN III was considered at least 2 mm away from the microinvasive complex. The ER, PR, bcl-2, and Bax immunoreactivity was scored as positive (>10% staining cells) and negative (<10% staining cells). No significant difference was observed between MIC and CIN III group concerning HPV infection and p53 polymorphism. The ER, PR, bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After multivariable analysis, coexpression of ER, PR, and bcl-2 was the only independent factor in defining low risk of progression for CIN III. Our study suggests that coexpression of ER, PR, and bcl-2 may be a useful tool in identifying the CIN III lesions with low risk of progression to cervical cancer.

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“…Estrogen receptor has been identified in normal and cancerous tissues of the cervix. [3][4][5][6][7][8] The growth of a human uterine cervical cancer cell line was stimulated by estradiol, and the estradiol-stimulated growth could be inhibited by tamoxifen, progesterone and medroxyprogesterone acetate, which exert anti-estrogenic action. 27) The conversion of estradiol to 16α-hydroxyestrone, a plausible risk factor for estrogen-responsive tumors, is elevated in cervical epithelial cells infected with human papillomavirus.…”

Section: Discussionmentioning

confidence: 99%

Relatively High Expression Ratio of Sex Hormone‐binding Globulin Exon VII Splicing Variant to Wild‐type mRNA in Human Uterine Cervical Cancers

Misao¹,

Nakanishi²,

Fujimoto³

et al. 1998

Japanese Journal of Cancer Research

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We have demonstrated the intracellular expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine cervical cancer using reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs proved they corresponded to the entire exon VII, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of the variant protein might be different from that of the wild-type SHBG. In uterine cervical cancers, the wild-type mRNA levels were lower (P< < < <0.01) and the ratio of the SHBG variant to wild-type mRNA levels was higher (P< < < <0.01) than in the normal cervix. In cervical adenocarcinomas, the wild-type mRNA levels were higher (P< < < <0.05) and the ratio of the SHBG variant to wild-type mRNA levels was lower (P< < < <0.05) than in cervical keratinizing squamous cell carcinomas. There was no difference in expression among the clinical stages of cervical cancers. These results suggest that a relative increase of intracellular variant SHBG protein in human uterine cervical cancers might be involved in the disruption of the normal estrogen dependence. Key words: Sex hormone-binding globulin -mRNA -Splicing variant -Uterine cervical cancerThere is clinical evidence of an important role for sex steroids in the reproductive events of the uterine cervix. 1, 2)The presence of steroid hormone receptors in normal cervix [3][4][5] and cervical cancer 6-8) has been reported, suggesting that the cellular biological characteristics of these tissues might be associated with the actions of sex steroid hormones.Sex hormone-binding globulin (SHBG) is a homodimeric glycoprotein, chiefly binding to estrogen and androgen in the circulation. 9) SHBG is responsible for the transport of these hormones in human blood, and alteration of its concentration is thought to modify the bioavailability of these steroids. However, abundant evidence indicates that SHBG-steroid complex also plays a direct role in intracellular steroidal actions in the target cells. [10][11][12][13][14] In addition, the expression of SHBG mRNA has been demonstrated in female reproductive organs and tumors, including uterine cervical cancer, [15][16][17][18][19] indicating its intracellular presence. The human SHBG gene is organized into eight exons separated by seven introns. 20) Screening of a human testis cDNA library revealed the presence of other clones markedly different from the full-length SHBG cDNA. 20) One of them, lacking a 208-base pair region, is an exon VII splicing variant of the SHBG gene. This clone encodes for a truncated form of SHBG, which lacks a part of the steroidbinding domain. 21) This variant is coexpressed in human uterine endometrium, 22) but its biological implication remains to be clarified.The aim of the present study was to investigate the presence of SHBG splicing variant and its biological implication in human uterine cervical cancers. MATERIALS AND METHODS MaterialsSpecimens of normal an...

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Steroid hormone receptors in carcinoma of the cervix

Cited by 35 publications

References 15 publications

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

Relatively High Expression Ratio of Sex Hormone‐binding Globulin Exon VII Splicing Variant to Wild‐type mRNA in Human Uterine Cervical Cancers

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