Limits...
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.


Related in: MedlinePlus

Distribution of SATB1 staining in primary tumours. Bar chart visualizing the relationship of nuclear SATB1 staining intensity with the estimated proportion of tumour cells expressing SATB1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3472180&req=5

Figure 2: Distribution of SATB1 staining in primary tumours. Bar chart visualizing the relationship of nuclear SATB1 staining intensity with the estimated proportion of tumour cells expressing SATB1.

Mentions: In 32/38 (84.2%) evaluable cases of benign-appearing fallopian tubal epithelium, no or very low levels of SATB1 expression could be detected (Figure1 A, B). In primary EOC, positive SATB1 expression was denoted in 35/151 (23.2%) evaluable cases, predominantly in fractions <50% and intensities ranging from weak to moderate (Figure1 C-H and Figure2), and always exceeding tubal expression. The associations of SATB1 expression with established clinicpathological factors and investigative markers is shown in Table1. SATB1 expression was significantly associated with lower histological grade (Spearman´s Rho = -0.22, p = 0.006) but not with age or clinical stage. SATB1 expression did not differ by histological subtype (data not shown). There was no significant correlation between SATB1 expression and expression of AR, ER, PR, Ki67, Chek1, Chek2, pChek2 or RBM3. A positive correlation was seen between SATB1 and DACH2 expression (R = 0.28, p = 0.001), pChek1 (R = 0.26, p = 0.001), and MCM3 expression (R = 0.17, p = 0.042).


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)

Distribution of SATB1 staining in primary tumours. Bar chart visualizing the relationship of nuclear SATB1 staining intensity with the estimated proportion of tumour cells expressing SATB1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Distribution of SATB1 staining in primary tumours. Bar chart visualizing the relationship of nuclear SATB1 staining intensity with the estimated proportion of tumour cells expressing SATB1.
Mentions: In 32/38 (84.2%) evaluable cases of benign-appearing fallopian tubal epithelium, no or very low levels of SATB1 expression could be detected (Figure1 A, B). In primary EOC, positive SATB1 expression was denoted in 35/151 (23.2%) evaluable cases, predominantly in fractions <50% and intensities ranging from weak to moderate (Figure1 C-H and Figure2), and always exceeding tubal expression. The associations of SATB1 expression with established clinicpathological factors and investigative markers is shown in Table1. SATB1 expression was significantly associated with lower histological grade (Spearman´s Rho = -0.22, p = 0.006) but not with age or clinical stage. SATB1 expression did not differ by histological subtype (data not shown). There was no significant correlation between SATB1 expression and expression of AR, ER, PR, Ki67, Chek1, Chek2, pChek2 or RBM3. A positive correlation was seen between SATB1 and DACH2 expression (R = 0.28, p = 0.001), pChek1 (R = 0.26, p = 0.001), and MCM3 expression (R = 0.17, p = 0.042).

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