Oestrogen receptor can be expressed by normal and dysplastic anal squamous epithelia but only rarely by anal squamous cell carcinoma

Wong, Newton A C S

doi:10.1111/his.13720

Cited by 3 publications

(5 citation statements)

References 4 publications

(9 reference statements)

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“…In the female sex, the squamous epithelium of the gynecologic tract shows decreased ER expression with the development of dysplasia and carcinoma 22. In a limited series of anal SqCC, Wong23 reported up to 4% ER expression. In our series, we noticed a lower expression of GATA-3 and ER in anal SqCC compared with the high-grade anal intraepithelial neoplasia (AIN3/carcinoma in situ); however, this finding did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

Coexpress of GATA-3 and ER in Anorectal and Head and Neck Squamous Cell Carcinoma Mimicking Metastatic Breast Cancer

Wang

Lu²,

Amin³

et al. 2020

Applied Immunohistochemistry &Amp; Molecular Morphology

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GATA binding protein 3 (GATA-3) is a sensitive marker for breast and urothelial carcinomas. In combination with the estrogen receptor (ER), it is often used for differential diagnosis of metastatic carcinomas of breast origin. In this study, we sought to characterize GATA-3 and ER expression in squamous cell carcinoma (SqCC) of various origins to compare with breast carcinoma. Sixty-four SqCC of anorectum ( 35), head and neck (15), lung (11), and breast (3) as well as urothelial carcinoma (31) were included. In anorectal and head and neck SqCC, GATA-3, and ER was observed in 23/50 (46.0%) and 18/50 (36.0%) of the cases, respectively. The expression of GATA-3 and ER were present in both male and female patients without significant sex predominance. In 2 metastatic SqCC, the GATA-3 and ER expressed similar immunoreactivity compatible with their anorectal primary. Progesterone receptor was only expressed in 2 anorectal SqCC and none of head and neck SqCC or urothelial carcinomas. None of the lung SqCC expressed GATA-3 or ER (0/11). p16 was expressed in the majority of head and neck (6/12) and anorectal SqCC (26/27). Our study demonstrated that the combination of GATA-3 and ER positivity is not entirely specific for breast carcinomas, since both stains are expressed in SqCC from anorectal and head and neck origins. Clinical workup for metastatic carcinoma of suspicious breast origin should be cognizant of other tumors with a similar immunohistochemical profile (ie, SqCC).

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Section: Discussionmentioning

confidence: 99%

Coexpress of GATA-3 and ER in Anorectal and Head and Neck Squamous Cell Carcinoma Mimicking Metastatic Breast Cancer

Wang

Lu²,

Amin³

et al. 2020

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…that ER is present in 4% of human anal SCC samples [26] and that estrogen is essential for activating cell proliferation of human epithelial SCC cell lines. [35] Thus, from these data, it is feasible that estrogens can ultimately influence Kras-induced non-papillomavirus anal SCC development, resulting in the sex-dependent development of anal SCC phenotype in female KC mice.…”

Section: Discussionmentioning

confidence: 98%

“…This remarkable finding indicates that female sex hormones are crucial for Kras G12D -driven anal SCC development in KC mice. Estrogen has a known role in the development of several tumors [26][27][28][29][30][31] and a correlation with Kras-mutant cancer [28][29][30][31]. Thus, we tested whether the anal SCC tumor development in a papillomavirus-negative context was driven by estrogen.…”

Section: Sex Hormone Dependence Of Anal Scc Formationmentioning

confidence: 99%

Sex-dependent development of Kras-induced anal squamous cell carcinoma in mice

Walcheck

Turco

Blaine-Sauer

et al. 2021

Preprint

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Anal squamous cell carcinoma (SCC) will be diagnosed in an estimated 9,080 adults in the United States this year, and rates have been rising over the last several decades. Most people that develop anal SCC have associated human papillomavirus (HPV) infection (∼85-95%), with approximately 5-15% of anal SCC cases occurring in HPV-negative patients from unknown etiology. This study identified and characterized a Kras-driven, female sex hormone-dependent development of anal squamous cell carcinoma (SCC) in the LSL-KrasG12D ; Pdx1-Cre (KC) mouse model that is not dependent on papillomavirus infection. One hundred percent of female KC mice develop anal SCC, while no male KC mice develop tumors. Both male and female KC anal tissue express Pdx1 and Cre-recombinase mRNA, and the activated mutant KrasG12D gene. Although the driver gene mutation KrasG12D is present in anus of both sexes, only female KC mice develop Kras-mutant induced anal SCC. To understand the sex-dependent differences, KC male mice were castrated and KC female mice were ovariectomized. Castrated KC males displayed an unchanged phenotype with no anal tumor formation. In contrast, ovariectomized KC females demonstrated a marked reduction in anal SCC development, with only 15% developing anal SCC. Finally, exogenous administration of estrogen rescued the tumor development in ovariectomized KC female mice and induced tumor development in castrated KC males. These results confirm that the anal SCC is estrogen mediated. The delineation of the role of female sex hormones in mediating mutant Kras to drive anal SCC pathogenesis highlights a subtype of anal SCC that is independent of papillomavirus infection. These findings may have clinical applicability for the papillomavirus-negative subset of anal SCC patients that typically respond poorly to standard of care chemoradiation.

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“…Estrogen dependence of anal SCC formation. Estrogen has a known role in the development of several tumors [27][28][29][30][31][32] and a correlation with Kras-mutant cancer [29][30][31][32]. Thus, we tested whether the anal SCC tumor development in a papillomavirus-negative context was driven by estrogen.…”

Section: Plos Onementioning

confidence: 99%

“…Furthermore, studies have shown estrogen mediates the development of mutant-Kras-driven endometrial cancer, ovarian cancer and vaginal SCC [30][31][32]. It has been shown that ERα is present in 4% of human anal SCC samples [27] and that estrogen is essential for activating cell proliferation of human epithelial SCC cell lines [36]. Thus, from these data, it is feasible that estrogens can ultimately influence Kras-induced non-papillomavirus anal SCC development, resulting in the sex-dependent development of anal SCC phenotype in female KC mice.…”

Section: Plos Onementioning

confidence: 99%

Sex-dependent development of Kras-induced anal squamous cell carcinoma in mice

et al. 2021

View full text Add to dashboard Cite

Anal squamous cell carcinoma (SCC) will be diagnosed in an estimated 9,080 adults in the United States this year, and rates have been rising over the last several decades. Most people that develop anal SCC have associated human papillomavirus (HPV) infection (~85–95%), with approximately 5–15% of anal SCC cases occurring in HPV-negative patients from unknown etiology. This study identified and characterized the Kras-driven, female sex hormone-dependent development of anal squamous cell carcinoma (SCC) in the LSL-KrasG12D; Pdx1-Cre (KC) mouse model that is not dependent on papillomavirus infection. One hundred percent of female KC mice develop anal SCC, while no male KC mice develop tumors. Both male and female KC anal tissue express Pdx1 and Cre-recombinase mRNA, and the activated mutant KrasG12D gene. Although the driver gene mutation KrasG12D is present in anus of both sexes, only female KC mice develop Kras-mutant induced anal SCC. To understand the sex-dependent differences, KC male mice were castrated and KC female mice were ovariectomized. Castrated KC males displayed an unchanged phenotype with no anal tumor formation. In contrast, ovariectomized KC females demonstrated a marked reduction in anal SCC development, with only 15% developing anal SCC. Finally, exogenous administration of estrogen rescued the tumor development in ovariectomized KC female mice and induced tumor development in castrated KC males. These results confirm that the anal SCC is estrogen mediated. The delineation of the role of female sex hormones in mediating mutant Kras to drive anal SCC pathogenesis highlights a subtype of anal SCC that is independent of papillomavirus infection. These findings may have clinical applicability for the papillomavirus-negative subset of anal SCC patients that typically respond poorly to standard of care chemoradiation.

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Oestrogen receptor can be expressed by normal and dysplastic anal squamous epithelia but only rarely by anal squamous cell carcinoma

Cited by 3 publications

References 4 publications

Coexpress of GATA-3 and ER in Anorectal and Head and Neck Squamous Cell Carcinoma Mimicking Metastatic Breast Cancer

Coexpress of GATA-3 and ER in Anorectal and Head and Neck Squamous Cell Carcinoma Mimicking Metastatic Breast Cancer

Sex-dependent development of Kras-induced anal squamous cell carcinoma in mice

Sex-dependent development of Kras-induced anal squamous cell carcinoma in mice

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