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Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma.

Ingram DR, Dillon LM, Lev DC, Lazar A, Demicco EG, Eisenberg BL, Miller TW - BMC Clin Pathol (2014)

Bottom Line: Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p< 0.05 was considered significant.Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis.Receptor expression was not associated with altered recurrence-free survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departments of Surgical Oncology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX, USA.

ABSTRACT

Background: Liposarcoma (LS) is the second-most common type of soft-tissue sarcoma. Despite advances in knowledge and treatment of this disease, there remains a need for more effective LS therapy. Steroid hormone receptors regulate metabolism in adipocytes. Estrogen receptor alpha (ER), progesterone receptor (PR), and androgen receptor (AR) have been implicated in the pathophysiology of other cancer types. We sought to comprehensively determine temporal expression patterns of these receptors in LS.

Methods: We analyzed 561 histologically subtyped LS specimens from 354 patients for expression of ER, PR, and AR by immunohistochemistry (IHC) using diagnostic-grade reagents and protocols. The fractions of positively stained tumor cells were scored within each specimen. IHC scores were compared across LS subtypes using the Kruskal-Wallis test, and subtypes were compared using Dunn's post-hoc test. Ages of patients with receptor-positive vs. -negative LS were compared by t-test. Genders and races were compared for hormone receptor positivity using Fisher's exact test and Chi-square analysis, respectively. Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p< 0.05 was considered significant.

Results: ER and AR were frequently expressed in LS, while few tumors expressed PR. Most of the ER + and AR + samples were of the well-differentiated LS subtype. A smaller fraction of de-differentiated LS expressed ER or AR, but expression was common within well-differentiated regions of tumors histologically classified as de-differentiated LS. In LS specimens from patients who underwent multiple surgeries over time, receptor expression frequently changed over time, which may be attributable in part to intratumor heterogeneity, varying degrees of de-differentiation, and biopsy bias. ER and AR were frequently co-expressed. Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis. Receptor expression was not associated with altered recurrence-free survival.

Conclusions: ER and AR are commonly expressed in LS, particularly in well-differentiated tumors. These data warrant further functional study to determine receptor function in LS, and the potential efficacy of anti-hormone therapies for the treatment of patients with LS.

No MeSH data available.


Related in: MedlinePlus

Steroid hormone receptor expression is most common in WDLS. A) LS specimens were scored for% positively-stained nuclei for ER, PR, and AR, then classified by histological subtype and binned according to score as indicated. B) ER and AR scores were compared between specimen subtypes. Colored bars indicate mean + SD. *p< 0.0001 by Dunn’s post-hoc test. C) Venn diagrams illustrating the number of WDLS and DDLS specimens with co-expression of hormone receptors using a threshold of 1% or 10% positively-stained nuclei.
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Figure 2: Steroid hormone receptor expression is most common in WDLS. A) LS specimens were scored for% positively-stained nuclei for ER, PR, and AR, then classified by histological subtype and binned according to score as indicated. B) ER and AR scores were compared between specimen subtypes. Colored bars indicate mean + SD. *p< 0.0001 by Dunn’s post-hoc test. C) Venn diagrams illustrating the number of WDLS and DDLS specimens with co-expression of hormone receptors using a threshold of 1% or 10% positively-stained nuclei.

Mentions: IHC staining of 561 specimens obtained from 379 LS tumors from 353 patients (characteristics listed in Table 1) revealed nuclear ER and AR expression in a significant number of cases (Figure 1). PR staining was less frequently observed. Using the stringent threshold of 10% positively-stained nuclei, we observed the following: 43.1% of WDLS, 17.5% of DDLS, 0% of PLS, and 5.2% of MLS were scored as ER+; 9.8% of WDLS, 7.6% of DDLS, 0% of PLS, and 5% of MLS were scored as PR+; 58.1% of WDLS, 24.1% of DDLS, 6.2% of PLS, and 9.1% of MLS were scored as AR + (Figure 2A). Using the threshold of 1% positively-stained nuclei used in the histological classification of breast cancer, we observed the following: 52.8% of WDLS, 22.5% of DDLS, 3.3% of PLS, and 10.4% of MLS were scored as ER+; 16.5% of WDLS, 10.2% of DDLS, 0% of PLS, and 9% of MLS were scored as PR+; 70% of WDLS, 36.2% of DDLS, 15.6% of PLS, and 19.2% of MLS were scored as AR + .


Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma.

Ingram DR, Dillon LM, Lev DC, Lazar A, Demicco EG, Eisenberg BL, Miller TW - BMC Clin Pathol (2014)

Steroid hormone receptor expression is most common in WDLS. A) LS specimens were scored for% positively-stained nuclei for ER, PR, and AR, then classified by histological subtype and binned according to score as indicated. B) ER and AR scores were compared between specimen subtypes. Colored bars indicate mean + SD. *p< 0.0001 by Dunn’s post-hoc test. C) Venn diagrams illustrating the number of WDLS and DDLS specimens with co-expression of hormone receptors using a threshold of 1% or 10% positively-stained nuclei.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4209467&req=5

Figure 2: Steroid hormone receptor expression is most common in WDLS. A) LS specimens were scored for% positively-stained nuclei for ER, PR, and AR, then classified by histological subtype and binned according to score as indicated. B) ER and AR scores were compared between specimen subtypes. Colored bars indicate mean + SD. *p< 0.0001 by Dunn’s post-hoc test. C) Venn diagrams illustrating the number of WDLS and DDLS specimens with co-expression of hormone receptors using a threshold of 1% or 10% positively-stained nuclei.
Mentions: IHC staining of 561 specimens obtained from 379 LS tumors from 353 patients (characteristics listed in Table 1) revealed nuclear ER and AR expression in a significant number of cases (Figure 1). PR staining was less frequently observed. Using the stringent threshold of 10% positively-stained nuclei, we observed the following: 43.1% of WDLS, 17.5% of DDLS, 0% of PLS, and 5.2% of MLS were scored as ER+; 9.8% of WDLS, 7.6% of DDLS, 0% of PLS, and 5% of MLS were scored as PR+; 58.1% of WDLS, 24.1% of DDLS, 6.2% of PLS, and 9.1% of MLS were scored as AR + (Figure 2A). Using the threshold of 1% positively-stained nuclei used in the histological classification of breast cancer, we observed the following: 52.8% of WDLS, 22.5% of DDLS, 3.3% of PLS, and 10.4% of MLS were scored as ER+; 16.5% of WDLS, 10.2% of DDLS, 0% of PLS, and 9% of MLS were scored as PR+; 70% of WDLS, 36.2% of DDLS, 15.6% of PLS, and 19.2% of MLS were scored as AR + .

Bottom Line: Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p< 0.05 was considered significant.Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis.Receptor expression was not associated with altered recurrence-free survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departments of Surgical Oncology, M.D. Anderson Cancer Center, University of Texas, 1515 Holcombe Blvd, Houston, TX, USA.

ABSTRACT

Background: Liposarcoma (LS) is the second-most common type of soft-tissue sarcoma. Despite advances in knowledge and treatment of this disease, there remains a need for more effective LS therapy. Steroid hormone receptors regulate metabolism in adipocytes. Estrogen receptor alpha (ER), progesterone receptor (PR), and androgen receptor (AR) have been implicated in the pathophysiology of other cancer types. We sought to comprehensively determine temporal expression patterns of these receptors in LS.

Methods: We analyzed 561 histologically subtyped LS specimens from 354 patients for expression of ER, PR, and AR by immunohistochemistry (IHC) using diagnostic-grade reagents and protocols. The fractions of positively stained tumor cells were scored within each specimen. IHC scores were compared across LS subtypes using the Kruskal-Wallis test, and subtypes were compared using Dunn's post-hoc test. Ages of patients with receptor-positive vs. -negative LS were compared by t-test. Genders and races were compared for hormone receptor positivity using Fisher's exact test and Chi-square analysis, respectively. Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p< 0.05 was considered significant.

Results: ER and AR were frequently expressed in LS, while few tumors expressed PR. Most of the ER + and AR + samples were of the well-differentiated LS subtype. A smaller fraction of de-differentiated LS expressed ER or AR, but expression was common within well-differentiated regions of tumors histologically classified as de-differentiated LS. In LS specimens from patients who underwent multiple surgeries over time, receptor expression frequently changed over time, which may be attributable in part to intratumor heterogeneity, varying degrees of de-differentiation, and biopsy bias. ER and AR were frequently co-expressed. Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis. Receptor expression was not associated with altered recurrence-free survival.

Conclusions: ER and AR are commonly expressed in LS, particularly in well-differentiated tumors. These data warrant further functional study to determine receptor function in LS, and the potential efficacy of anti-hormone therapies for the treatment of patients with LS.

No MeSH data available.


Related in: MedlinePlus