Limits...
Prognostic and treatment predictive significance of SATB1 and SATB2 expression in pancreatic and periampullary adenocarcinoma.

Elebro J, Heby M, Gaber A, Nodin B, Jonsson L, Fristedt R, Uhlén M, Jirström K, Eberhard J - J Transl Med (2014)

Bottom Line: Expression of SATB1 was an independent predictor of a significantly shorter RFS and OS in pancreatobiliary type, but not in intestinal type adenocarcinomas.Moreover, SATB1 expression predicted an improved response to adjuvant chemotherapy in both tumour types.The small number of cases with positive SATB2 expression did not allow for any firm conclusions on its prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. jacob.elebro@med.lu.se.

ABSTRACT

Background: Pancreatic cancer and other pancreaticobiliary type periampullary adenocarcinomas have a dismal prognosis even after resection and neoadjuvant chemotherapy. Intestinal type periampullary adenocarcinomas generally have a better prognosis, but little is known on optimal neoadjuvant and adjuvant treatment. New prognostic and treatment predictive biomarkers are needed for improved treatment stratification of patients with both types of periampullary adenocarcinoma. Expression of the Special AT-rich sequence-binding protein 1 (SATB1) has been demonstrated to confer a worse prognosis in several tumour types, whereas its close homologue SATB2 is a proposed diagnostic and favourable prognostic marker for colorectal cancer. The prognostic value of SATB1 and SATB2 expression in periampullary adenocarcinoma has not yet been described.

Methods: Immunohistochemical expression of SATB1 and SATB2 was analysed in tissue microarrays with primary tumours and a subset of paired lymph node metastases from 175 patients operated with pancreaticoduodenectomy for periampullary adenocarcinoma. Kaplan-Meier and Cox regression analysis were applied to explore the impact of SATB1 and SATB2 expression on recurrence free survival (RFS) and overall survival (OS).

Results: Positive expression of SATB1 was denoted in 16/106 primary pancreatobiliary type tumours and 11/65 metastases, and in 15/63 primary intestinal type tumours and 4/26 metastases, respectively. Expression of SATB1 was an independent predictor of a significantly shorter RFS and OS in pancreatobiliary type, but not in intestinal type adenocarcinomas. Moreover, SATB1 expression predicted an improved response to adjuvant chemotherapy in both tumour types. SATB2-expression was seen in 3/107 pancreatobiliary type primary tumours, and in 8/61 intestinal type primary tumours. The small number of cases with positive SATB2 expression did not allow for any firm conclusions on its prognostic value.

Conclusions: These findings demonstrate the potential utility of SATB1 as a prognostic and predictive biomarker for chemotherapy response in both intestinal type and pancreatobiliary type periampullary adenocarcinomas, including pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier estimates of overall survival (A) and recurrence free survival (B) in pancreatobiliary type tumours stratified by SATB1-expression and corresponding curves stratified for adjuvant chemotherapy (C-D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4232660&req=5

Fig2: Kaplan-Meier estimates of overall survival (A) and recurrence free survival (B) in pancreatobiliary type tumours stratified by SATB1-expression and corresponding curves stratified for adjuvant chemotherapy (C-D).

Mentions: As demonstrated in Figure 2A-B, Kaplan-Meier analysis revealed that SATB1 expression was prognostic for OS and RFS in the PB-group of tumours. SATB1 positive cases had a shorter OS compared with SATB1 negative cases, median 16.7 months (interquartile range, IQR 9.9-25.1) vs 27.3 months (IQR 15.8-46.3) (logrank p = 0.004), and also a shorter RFS, median 9.0 months (IQR 5.1-18.8) vs 16.8 months (IQR 8.0-28.5) (logrank p = 0.018). As demonstrated in Table 3, the significant associations of SATB1 expression with survival were confirmed in Cox univariable analysis for both OS (HR = 2.11; 95% confidence interval, CI 1.25-3.56) and RFS (HR = 1.87; 95% CI 1.10-3.18), and this significance was retained for OS in multivariable analysis (HR = 1.79; 95% CI 1.05-3.05).Figure 2


Prognostic and treatment predictive significance of SATB1 and SATB2 expression in pancreatic and periampullary adenocarcinoma.

Elebro J, Heby M, Gaber A, Nodin B, Jonsson L, Fristedt R, Uhlén M, Jirström K, Eberhard J - J Transl Med (2014)

Kaplan-Meier estimates of overall survival (A) and recurrence free survival (B) in pancreatobiliary type tumours stratified by SATB1-expression and corresponding curves stratified for adjuvant chemotherapy (C-D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232660&req=5

Fig2: Kaplan-Meier estimates of overall survival (A) and recurrence free survival (B) in pancreatobiliary type tumours stratified by SATB1-expression and corresponding curves stratified for adjuvant chemotherapy (C-D).
Mentions: As demonstrated in Figure 2A-B, Kaplan-Meier analysis revealed that SATB1 expression was prognostic for OS and RFS in the PB-group of tumours. SATB1 positive cases had a shorter OS compared with SATB1 negative cases, median 16.7 months (interquartile range, IQR 9.9-25.1) vs 27.3 months (IQR 15.8-46.3) (logrank p = 0.004), and also a shorter RFS, median 9.0 months (IQR 5.1-18.8) vs 16.8 months (IQR 8.0-28.5) (logrank p = 0.018). As demonstrated in Table 3, the significant associations of SATB1 expression with survival were confirmed in Cox univariable analysis for both OS (HR = 2.11; 95% confidence interval, CI 1.25-3.56) and RFS (HR = 1.87; 95% CI 1.10-3.18), and this significance was retained for OS in multivariable analysis (HR = 1.79; 95% CI 1.05-3.05).Figure 2

Bottom Line: Expression of SATB1 was an independent predictor of a significantly shorter RFS and OS in pancreatobiliary type, but not in intestinal type adenocarcinomas.Moreover, SATB1 expression predicted an improved response to adjuvant chemotherapy in both tumour types.The small number of cases with positive SATB2 expression did not allow for any firm conclusions on its prognostic value.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden. jacob.elebro@med.lu.se.

ABSTRACT

Background: Pancreatic cancer and other pancreaticobiliary type periampullary adenocarcinomas have a dismal prognosis even after resection and neoadjuvant chemotherapy. Intestinal type periampullary adenocarcinomas generally have a better prognosis, but little is known on optimal neoadjuvant and adjuvant treatment. New prognostic and treatment predictive biomarkers are needed for improved treatment stratification of patients with both types of periampullary adenocarcinoma. Expression of the Special AT-rich sequence-binding protein 1 (SATB1) has been demonstrated to confer a worse prognosis in several tumour types, whereas its close homologue SATB2 is a proposed diagnostic and favourable prognostic marker for colorectal cancer. The prognostic value of SATB1 and SATB2 expression in periampullary adenocarcinoma has not yet been described.

Methods: Immunohistochemical expression of SATB1 and SATB2 was analysed in tissue microarrays with primary tumours and a subset of paired lymph node metastases from 175 patients operated with pancreaticoduodenectomy for periampullary adenocarcinoma. Kaplan-Meier and Cox regression analysis were applied to explore the impact of SATB1 and SATB2 expression on recurrence free survival (RFS) and overall survival (OS).

Results: Positive expression of SATB1 was denoted in 16/106 primary pancreatobiliary type tumours and 11/65 metastases, and in 15/63 primary intestinal type tumours and 4/26 metastases, respectively. Expression of SATB1 was an independent predictor of a significantly shorter RFS and OS in pancreatobiliary type, but not in intestinal type adenocarcinomas. Moreover, SATB1 expression predicted an improved response to adjuvant chemotherapy in both tumour types. SATB2-expression was seen in 3/107 pancreatobiliary type primary tumours, and in 8/61 intestinal type primary tumours. The small number of cases with positive SATB2 expression did not allow for any firm conclusions on its prognostic value.

Conclusions: These findings demonstrate the potential utility of SATB1 as a prognostic and predictive biomarker for chemotherapy response in both intestinal type and pancreatobiliary type periampullary adenocarcinomas, including pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus