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Expression of the global regulator SATB1 is an independent factor of poor prognosis in high grade epithelial ovarian cancer.

Nodin B, Hedner C, Uhlén M, Jirström K - J Ovarian Res (2012)

Bottom Line: This association remained significant in multivariable analysis, adjusted for age and clinical stage (HR = 2.20 and HR = 2.06, respectively).These results demonstrate that SATB1 expression is an independent factor of poor prognosis in high grade EOC and correlates in vivo with cellular processes involved in the maintenance of DNA integrity.The functional basis for these observations merits further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Sciences, Division of Pathology, Lund University, Lund, SE-221 85, Sweden. bjorn.nodin@med.lu.se.

ABSTRACT

Background: The global gene regulator Special AT-rich sequence-binding protein1 (SATB1) has been reported to reprogramme tumour cells into a more malignant phenotype and associate with poor clinical outcome in several cancer forms. In this study, we investigated the molecular correlates and prognostic impact of SATB1 expression in human epithelial ovarian cancer (EOC).

Findings: Immunohistochemical expression of SATB1 was examined in tissue microarrays with tumours from 151 incident EOC cases from two prospective, population-based cohorts. Benign-appearing fallopian tube epithelium from 32 cases was also analyzed. A multiplier of nuclear fraction and staining intensity of SATB1 was calculated. While barely expressed in tubal epithelium, nuclear SATB1 expression was denoted in 35/151 (23.2%) EOC cases. Spearman´s Rho test revealed an inverse correlation between SATB1 expression and histological grade (R = -0.22, p = 0.006) and a positive correlation with expression of dachshund 2 protein (R = 0.28, p = 0.001), phosphorylated Chek1 (R = 0.26, p = 0.002) and minichromosome maintenance protein 3 (R = 0.17, p = 0.042). Univariable Cox regression analysis revealed that SATB1 expression, while not prognostic in the full cohort, was associated with a reduced ovarian cancer-specific survival and 5-year overall survival in high grade tumours (n = 105) (HR = 2.14 and HR = 1.96, respectively). This association remained significant in multivariable analysis, adjusted for age and clinical stage (HR = 2.20 and HR = 2.06, respectively).

Conclusions: These results demonstrate that SATB1 expression is an independent factor of poor prognosis in high grade EOC and correlates in vivo with cellular processes involved in the maintenance of DNA integrity. The functional basis for these observations merits further investigation.

No MeSH data available.


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Kaplan-Meier estimates of survival according to SATB1 expression in patients with high-grade tumours. Kaplan Meier analysis of (A) ovarian cancer specific and (B) 5-year overall survival in strata according to negative and positive SATB1 expression in patients with high-grade tumours (n = 105).
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Figure 3: Kaplan-Meier estimates of survival according to SATB1 expression in patients with high-grade tumours. Kaplan Meier analysis of (A) ovarian cancer specific and (B) 5-year overall survival in strata according to negative and positive SATB1 expression in patients with high-grade tumours (n = 105).

Mentions: Kaplan-Meier analysis revealed no significant association of SATB1 expression with OCSS or OS in the full cohort (data not shown) but stratified analysis according to tumour grade revealed that positive SATB1 expression was a significant factor of poor prognosis in high grade tumours (n = 105), regardless of histological subtype (logrank p = 0.004 for OCSS and logrank p = 0.015 for 5-year OS, (Figure3 A-B). These associations were confirmed in univariable and multivariable Cox regression analysis, adjusted for age and clinical stage (Table2). SATB1 expression was not prognostic in low-grade tumours or in subgroups according to histological type (data not shown).


Expression of the global regulator SATB1 is an independent factor of poor prognosis in high grade epithelial ovarian cancer.

Nodin B, Hedner C, Uhlén M, Jirström K - J Ovarian Res (2012)

Kaplan-Meier estimates of survival according to SATB1 expression in patients with high-grade tumours. Kaplan Meier analysis of (A) ovarian cancer specific and (B) 5-year overall survival in strata according to negative and positive SATB1 expression in patients with high-grade tumours (n = 105).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472180&req=5

Figure 3: Kaplan-Meier estimates of survival according to SATB1 expression in patients with high-grade tumours. Kaplan Meier analysis of (A) ovarian cancer specific and (B) 5-year overall survival in strata according to negative and positive SATB1 expression in patients with high-grade tumours (n = 105).
Mentions: Kaplan-Meier analysis revealed no significant association of SATB1 expression with OCSS or OS in the full cohort (data not shown) but stratified analysis according to tumour grade revealed that positive SATB1 expression was a significant factor of poor prognosis in high grade tumours (n = 105), regardless of histological subtype (logrank p = 0.004 for OCSS and logrank p = 0.015 for 5-year OS, (Figure3 A-B). These associations were confirmed in univariable and multivariable Cox regression analysis, adjusted for age and clinical stage (Table2). SATB1 expression was not prognostic in low-grade tumours or in subgroups according to histological type (data not shown).

Bottom Line: This association remained significant in multivariable analysis, adjusted for age and clinical stage (HR = 2.20 and HR = 2.06, respectively).These results demonstrate that SATB1 expression is an independent factor of poor prognosis in high grade EOC and correlates in vivo with cellular processes involved in the maintenance of DNA integrity.The functional basis for these observations merits further investigation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Sciences, Division of Pathology, Lund University, Lund, SE-221 85, Sweden. bjorn.nodin@med.lu.se.

ABSTRACT

Background: The global gene regulator Special AT-rich sequence-binding protein1 (SATB1) has been reported to reprogramme tumour cells into a more malignant phenotype and associate with poor clinical outcome in several cancer forms. In this study, we investigated the molecular correlates and prognostic impact of SATB1 expression in human epithelial ovarian cancer (EOC).

Findings: Immunohistochemical expression of SATB1 was examined in tissue microarrays with tumours from 151 incident EOC cases from two prospective, population-based cohorts. Benign-appearing fallopian tube epithelium from 32 cases was also analyzed. A multiplier of nuclear fraction and staining intensity of SATB1 was calculated. While barely expressed in tubal epithelium, nuclear SATB1 expression was denoted in 35/151 (23.2%) EOC cases. Spearman´s Rho test revealed an inverse correlation between SATB1 expression and histological grade (R = -0.22, p = 0.006) and a positive correlation with expression of dachshund 2 protein (R = 0.28, p = 0.001), phosphorylated Chek1 (R = 0.26, p = 0.002) and minichromosome maintenance protein 3 (R = 0.17, p = 0.042). Univariable Cox regression analysis revealed that SATB1 expression, while not prognostic in the full cohort, was associated with a reduced ovarian cancer-specific survival and 5-year overall survival in high grade tumours (n = 105) (HR = 2.14 and HR = 1.96, respectively). This association remained significant in multivariable analysis, adjusted for age and clinical stage (HR = 2.20 and HR = 2.06, respectively).

Conclusions: These results demonstrate that SATB1 expression is an independent factor of poor prognosis in high grade EOC and correlates in vivo with cellular processes involved in the maintenance of DNA integrity. The functional basis for these observations merits further investigation.

No MeSH data available.


Related in: MedlinePlus