Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis

Charalampoudis, Petros; Agrogiannis, George; Kontzoglou, Konstantinos; Kouraklis, Gregorios; Sotiropoulos, Georgios C.

doi:10.1016/j.ejso.2017.05.012

Cited by 9 publications

(5 citation statements)

References 18 publications

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“…Literature regarding the clinical significance of THR at the protein level is still limited. A recent study performed in 41 invasive BC tissues suggested that nuclear THRα is down-regulated during breast carcinogenesis [23]. Other studies highlighted the role of THRβ as a tumor suppressor in BC.…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Shao¹,

Kühn²,

Mayr

et al. 2020

IJMS

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The aim of this study was to investigate the expression of thyroid hormone receptor β1 (THRβ1) by immunohistochemistry in breast cancer (BC) tissues and to correlate the results with clinico-biological parameters. In a well-characterized cohort of 274 primary BC patients, THRβ1 was widely expressed with a predominant nuclear location, although cytoplasmic staining was also frequently observed. Both nuclear and cytoplasmic THRβ1 were correlated with high-risk BC markers such as human epidermal growth factor receptor 2 (HER2), Ki67 (also known as MKI67), prominin-1 (CD133), and N-cadherin. Overall survival analysis demonstrated that cytoplasmic THRβ1 was correlated with favourable survival (p = 0.015), whereas nuclear THRβ1 had a statistically significant correlation with poor outcome (p = 0.038). Interestingly, in our cohort, nuclear and cytoplasmic THRβ1 appeared to be independent markers either for poor (p = 0.0004) or for good (p = 0.048) prognosis, respectively. Altogether, these data indicate that the subcellular expression of THRβ1 may play an important role in oncogenesis. Moreover, the expression of nuclear THRβ1 is a negative outcome marker, which may help to identify high-risk BC subgroups.

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Section: Introductionmentioning

confidence: 99%

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Shao¹,

Kühn²,

Mayr

et al. 2020

IJMS

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“…In more recent literature, Jerzak et al [ 14 ] found the highest survival among women with low THRα-1 and high THRα-2 expression, supporting that claim. Why some breast cancer express more THRα-2 is not known, but Charalampoudis et al [ 28 ] found that the combined expression of THRα-1 and 2 was lower in invasive ductal breast carcinoma compared to normal breast epithelium, suggesting a loss of expression along with malignant transformation. It is also noteworthy that the association between survival and THRα-2 expression was inversed when looking only at ER-negative tumors.…”

Section: Discussionmentioning

confidence: 99%

Low thyroid hormone receptor alpha-2 (THRα-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality

et al. 2021

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Background The active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The present study evaluates tumor-specific THRα-2 expression in invasive breast cancers and its association with tumor characteristics and long-term mortality in a large population. Method The Malmö Diet and Cancer Study (MDCS), a population-based cohort in Sweden that included 17,035 women from 1991 to 1996, was used. Women diagnosed with breast cancer during 1991–2010 were eligible for inclusion. A tissue micro array was constructed from stored tumor material and stained for THRα-2 using immunohistochemistry. Tumors from 654 patients were scored regarding the intensity and the fraction of cells stained, then dichotomized into low or high expression. Date and cause of death were collected up until 2018-12-31. Tumor- and patient characteristics were available from the MDCS. Missing data was imputed using chained equations. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for low vs high expression of THRα-2 related to specific tumor factors. Mortality was evaluated with Kaplan–Meier curves and Cox regression, rendering hazard ratios (HRs). Analyses were also stratified for estrogen receptor (ER) status. Results We found strong evidence of an association between low THRα-2 and unfavorable tumor characteristics, including estrogen receptor negativity: OR 4.04 (95% CI 2.28–7.15) and tumor size > 20–50 mm: OR 2.20 (95% CI 1.39–3.49). We found evidence of increased breast cancer-specific mortality for women with low THRα-2, HR 1.38 (95% CI 0.96–1.99), which remained after adjusting for age at diagnosis, HR 1.48 (95% CI 1.03–2.14), but not after adjusting for relevant prognostic factors, HR 0.98 (95% CI 0.66–1.45). THRα-2 expression in ER-negative tumors had an inverse correlation with overall mortality, HR 0.27 (95% CI 0.11–0.65). Conclusion Low tumor-specific THRα-2 expression was in this study associated with prognostically unfavorable tumor characteristics and a higher mortality in breast cancer, but not independent from other prognostic factors.

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“…TRα2 expression correlated with expressions of ER and PR, with HER2 negativity, and with improved 5-year OS [61]. However, another study showed no clear association between TRα expression and breast cancer intrinsic sub-types or hormonal profiles [57]. ER and TRs were concomitantly expressed in a study of breast cancer tissues from 12 patients [62].…”

Section: Expression Of Trs Tshr and Related Proteins In Human Breast ...mentioning

confidence: 97%

“…The expression of thyroid receptor TRα1 was reduced in breast cancers compared with normal, benign (fibrocystic changes and fibroadenomas) and lactating breast tissues [56]. TRα expression was even lower in more sizable and higher-grade breast cancers compared with smaller and lower-grade ones [57]. The cellular localization of TRα and TRβ was examined by immunohistochemistry in a study of 148 samples from normal breast tissues, benign breast lesions and in situ or invasive breast cancers [58].…”

Section: Expression Of Trs Tshr and Related Proteins In Human Breast ...mentioning

confidence: 99%

The TSH/Thyroid Hormones Axis and Breast Cancer

Voutsadakis

2022

JCM

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Breast cancer, the most prevalent female carcinoma, is characterized by the expression of steroid nuclear receptors in a subset of cases. The most important nuclear receptor with prognostic and therapeutic implications is the Estrogen Receptor (ER), which is expressed in about three out of four breast cancers. The Progesterone Receptor (PR) and the Androgen Receptor (AR) are also commonly expressed. Moreover, non-steroid nuclear receptors, including the vitamin D receptor (VDR) and the thyroid receptors (TRs), are also present in breast cancers and have pathophysiologic implications. Circulating thyroid hormones may influence breast cancer risk and breast cancer cell survival, through ligating their canonical receptors TRα and TRβ but also through additional membrane receptors that are expressed in breast cancer. The expression of TR subtypes and their respective isotypes have diverse effects in breast cancers through co-operation with ER and influence on other cancer-associated pathways. Other components of the TSH/thyroid hormone axis, such as TSH and selenoiodinase enzymes, have putative effects in breast cancer pathophysiology. This paper reviews the pathophysiologic and prognostic implications of the thyroid axis in breast cancer and provides a brief therapeutic perspective.

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Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis

Cited by 9 publications

References 18 publications

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Low thyroid hormone receptor alpha-2 (THRα-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality

The TSH/Thyroid Hormones Axis and Breast Cancer

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