Prognostic impact of Skp2, ER and PGR in male and female patients with soft tissue sarcomas

Sørbye, Sveinung Wergeland; Kilvaer, Thomas K.; Valkov, Andrej; Dønnem, Tom; Smeland, Eivind; Al-Shibli, Khalid; Bremnes, Roy M.; Busund, Lill-Tove

doi:10.1186/1472-6890-13-9

Cited by 5 publications

(10 citation statements)

References 20 publications

(24 reference statements)

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“…32 Furthermore, S-phase kinase-associated protein 2 expression is a negative gender-specific predictor of survival for STS patients in an estrogen receptor/progesterone receptor (ER/PGR)-associated manner. 50 In the study by Sorbye et al, ER (in women) and PGR (in men) were also predictors of disease-specific survival. Therefore, there is an urgent need to study the molecular mechanisms and clinical consequences of gender-specific gene expression in tumors of mesenchymal derivation in detail.…”

Section: Discussionmentioning

confidence: 94%

“…We have recently demonstrated that a gender‐specific low expression of stem cell‐associated Piwi‐like genes is significantly associated with disease‐specific survival in STS patients . Furthermore, S‐phase kinase‐associated protein 2 expression is a negative gender‐specific predictor of survival for STS patients in an estrogen receptor/progesterone receptor (ER/PGR)‐associated manner . In the study by Sorbye et al ., ER (in women) and PGR (in men) were also predictors of disease‐specific survival.…”

Section: Discussionmentioning

confidence: 99%

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High coexpression of CCL2 and CX3CL1 is gender‐specifically associated with good prognosis in soft tissue sarcoma patients

Kehlen

Greither

Wach

et al. 2014

Intl Journal of Cancer

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Chemokines are involved in both the negative and positive regulation of inflammatory processes, angiogenesis and cancer/cancer stem cell proliferation as well as the chemoattraction of tumor cells to metastatic sites. The aim of this study was to measure the mRNA expression levels of three chemokines, CCL2, CCL7 and CX3CL1, in soft tissue sarcomas (STSs) and to assess the correlations between these levels as well as their correlations with clinicopathological data and the disease-specific survival of STS patients. The mRNA levels of CCL2, CCL7 and CX3CL1 were analyzed in tumor tissues from 126 STS patients using qPCR. Low mRNA expression of CCL2 and CX3CL1 was significantly correlated with a worse prognosis (RR 5 1.98; p 5 0.019 and RR 5 2.10; p 5 0.014; multivariate Cox's regression analysis). A combined low expression of CCL2 and CX3CL1 was associated with a significantly increased risk of tumor-related death as compared to patients with high expression levels of both chemokines (RR 5 3.08; p 5 0.003). A gender-specific multivariate analysis revealed that female STS patients with low CX3CL1 mRNA expression had a 3.46-fold increased risk of death (p 5 0.004). Low expression of both CCL2 and CX3CL1 mRNAs resulted in an additive 5.37-fold increased risk of tumor-related death (p 5 0.003) as compared to those with high expression of both parameters in female patients. In conclusion, this is the first study to show a significant correlation between combined low expression of CCL2 and CX3CL1 and a poor prognosis for STS patients, particularly in female patients.Soft tissue sarcomas (STSs) are a heterogeneous group of malignant mesenchymal tumors. 1,2 Clinically relevant prognostic factors include tumor size, tumor grade, the localization of the primary tumor 3 and the type of tumor resection. In addition, several molecular factors with prognostic impact have been identified (reviewed in Refs. 4 and 5). However, there is still an urgent need to characterize further prognosisassociated molecular factors for an improved prognostication and treatment management. In several cancer types, chemokines have been discussed as biomarkers for detecting early metastasis, have been associated with tumor progression, and have been suggested as potential therapeutic targets. Chemokines represent a group of chemotactic cytokines responsible for orchestrating cell recruitment under both homeostatic and inflammatory conditions. The small (8-10 kDa) chemokine proteins are classified into four highly conserved groups-C, CC, CXC and CX3C-based on the position of the first two cysteines that are adjacent to the amino terminus. 6 The binding of the chemokine ligand to its seventransmembrane G-protein-coupled receptor activates downstream signaling that leads to cell movement in development, inflammation, wound healing and cancer. 7 Oncogenic

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

High coexpression of CCL2 and CX3CL1 is gender‐specifically associated with good prognosis in soft tissue sarcoma patients

Kehlen

Greither

Wach

et al. 2014

Intl Journal of Cancer

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“…Since lipogenic metabolism is heavily influenced by steroid hormones [ 7 ], and adipocytes express nuclear hormone receptors and steroidogenic enzymes such as aromatase [ 8 , 9 ], we postulated that LS cells may similarly express such receptors. Prior studies in limited numbers of patients reported expression of steroid hormone receptors in a fraction of LS cases [ 10 - 17 ]. To expand upon and clarify these findings, we analyzed 561 LS specimens acquired from 353 patients in the largest LS cohort reported to-date to determine the frequencies of expression of estrogen receptor alpha (ER), progesterone receptor (PR), and androgen receptor (AR).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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BackgroundLiposarcoma (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.MethodsWe 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.ResultsER 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.ConclusionsER 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.

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“…In men, but not women, estrogen receptor positive/progesterone receptor negative co-expression profile was an independent negative prognostic factor for disease-specific survival. [ 18 ] Another study by Valkov et al . showed that estrogen receptor positivity was a significant favorable indicator for disease-specific survival in women ( P = 0.017), while progesterone receptor positivity had inverse impact in men ( P = 0.001).…”

Section: Discussionmentioning

confidence: 99%

Nonrhabdomyosarcomatous abdominopelvic sarcomas: Analysis of prognostic factors

Iqbal

Shukla

Deo

et al. 2016

Indian J Med Paediatr Oncol

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Background:Data concerning treatment outcome and prognostic factors in sarcomas of abdomen and pelvis are sparse in literature. Methods and Results:Of 696 patients with nonrhabdomyosarcomatous soft tissue sarcoma registered at our center between June 2003 and December 2012, 112 (16%) patients of sarcomas arising from abdomen and pelvis were identified, of which 88 patients were analyzed for treatment outcome and prognostic factors. The median age was 40 years (range: 1–78 years) with a male: female ratio of 0.7:1. Twenty-one (24%) patients were metastatic at baseline. The most common tumor sites were retroperitoneum in 70% patients and abdominal wall in 18% patients. Leiomyosarcoma was the most common histological subtype in 36% patients followed by liposarcoma in 17% patients. Thirty-five (40%) patients had Grade III tumors. Forty-six (52%) patients underwent surgical resection. At a median follow-up of 43 months (range: 2–94 months), the 5-year event-free survival (EFS) and overall survival (OS) were 35% and 42%, with a median of 22 months and 43 months, respectively. Multivariate analysis identified male gender (P - 0.03, hazard ratio [HR] - 0.46, 95% confidence interval [CI] - 0.23–0.92), baseline metastatic disease (P - 0.01, HR - 2.98, 95% CI - 1.27–6.98) and Grade III tumors (P - 0.02, HR - 1.84, 95% CI - 1.08–3.13) as factors associated with poor EFS, whereas baseline metastatic disease (P < 0.001, HR - 5.45, 95% CI - 2.31–12.87) and unresectability (P - 0.01, HR - 2.72, 95% CI - 1.27–5.83) were associated with poor OS.Conclusion:This is a single-institutional study of patients with abdominopelvic sarcomas where gender was identified as a new factor affecting survival apart from baseline presentation, histologic grade, and surgical resection.

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Prognostic impact of Skp2, ER and PGR in male and female patients with soft tissue sarcomas

Cited by 5 publications

References 20 publications

High coexpression of CCL2 and CX3CL1 is gender‐specifically associated with good prognosis in soft tissue sarcoma patients

High coexpression of CCL2 and CX3CL1 is gender‐specifically associated with good prognosis in soft tissue sarcoma patients

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

Nonrhabdomyosarcomatous abdominopelvic sarcomas: Analysis of prognostic factors

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