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Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma.

Zhu Z, Yu W, Fu X, Sun M, Wei Q, Li D, Chen H, Xiang J, Li H, Zhang Y, Zhao W, Zhao K - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS). p-EGFR expression was correlated statistically with all of the other phosphorylated markers.Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS.Increased expression of p-AKT1 was associated with decreased patient survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. zfeizhu@aliyun.com.

ABSTRACT

Background: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).

Methods: Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).

Results: p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.

Conclusion: Activation of AKT1 was associated with poor prognosis in ESCC.

No MeSH data available.


Related in: MedlinePlus

Representative findings on immunohistochemical staining for the tested biomarkers (original magnification × 200): EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3
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Fig1: Representative findings on immunohistochemical staining for the tested biomarkers (original magnification × 200): EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3

Mentions: TMAs were constructed in collaboration with the Department of Pathology at our hospital according to established methods [13]. For each patient, the tumor was identified on the original hematoxylin and eosin-stained (H&E) slides, and the corresponding formalin-fixed, paraffin-embedded tissue blocks were obtained. With use of a UATM-272A Tissue Microarrayer (Unitma, Seoul, Korea), three 1-mm tissue cores which were punched from various areas of the predominant tumor population and one 1-mm normal tissue cone which were punched from the normal areas around tumor for each patient and deposited into a 12 ×10 TMA block (120 cores). IHC staining was performed on 4-μm paraffin-embedded sections from TMA blocks by the standard Envision method using a panel of antibodies: EGFR (113, dilution 1:50; Dako), AKT1 (C73H10, dilution 3 μg/ml; Cell Signaling), AKT2 (302501, dilution 25 μg/ml; R&D), ERK1 (Y72, dilution 1:100; Abcam), ERK2 (E460, dilution 1:250; Abcam), STAT3 (E121-21, dilution 1:50; Abcam), phosphorylated-EGFR (p-EGFR) (Tyr1068) (EP774Y, dilution 1:250; Abcam), phosphorylated-AKT1 (p-AKT1) (Ser473) (EP2109Y, dilution 1:100; Abcam), phosphorylated-AKT2 (p-AKT2) (Ser474) (D3H2, dilution 1:100; Cell Signaling), phosphorylated-ERK1/2 (p-ERK1/2) (MAPK-YT, dilution 1:100; Abcam), and phosphorylated- STAT3 (p-STAT3) (EP2147Y, dilution 1:250; Abcam) (Fig. 1).Fig. 1


Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma.

Zhu Z, Yu W, Fu X, Sun M, Wei Q, Li D, Chen H, Xiang J, Li H, Zhang Y, Zhao W, Zhao K - J. Exp. Clin. Cancer Res. (2015)

Representative findings on immunohistochemical staining for the tested biomarkers (original magnification × 200): EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4559941&req=5

Fig1: Representative findings on immunohistochemical staining for the tested biomarkers (original magnification × 200): EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3
Mentions: TMAs were constructed in collaboration with the Department of Pathology at our hospital according to established methods [13]. For each patient, the tumor was identified on the original hematoxylin and eosin-stained (H&E) slides, and the corresponding formalin-fixed, paraffin-embedded tissue blocks were obtained. With use of a UATM-272A Tissue Microarrayer (Unitma, Seoul, Korea), three 1-mm tissue cores which were punched from various areas of the predominant tumor population and one 1-mm normal tissue cone which were punched from the normal areas around tumor for each patient and deposited into a 12 ×10 TMA block (120 cores). IHC staining was performed on 4-μm paraffin-embedded sections from TMA blocks by the standard Envision method using a panel of antibodies: EGFR (113, dilution 1:50; Dako), AKT1 (C73H10, dilution 3 μg/ml; Cell Signaling), AKT2 (302501, dilution 25 μg/ml; R&D), ERK1 (Y72, dilution 1:100; Abcam), ERK2 (E460, dilution 1:250; Abcam), STAT3 (E121-21, dilution 1:50; Abcam), phosphorylated-EGFR (p-EGFR) (Tyr1068) (EP774Y, dilution 1:250; Abcam), phosphorylated-AKT1 (p-AKT1) (Ser473) (EP2109Y, dilution 1:100; Abcam), phosphorylated-AKT2 (p-AKT2) (Ser474) (D3H2, dilution 1:100; Cell Signaling), phosphorylated-ERK1/2 (p-ERK1/2) (MAPK-YT, dilution 1:100; Abcam), and phosphorylated- STAT3 (p-STAT3) (EP2147Y, dilution 1:250; Abcam) (Fig. 1).Fig. 1

Bottom Line: Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS). p-EGFR expression was correlated statistically with all of the other phosphorylated markers.Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS.Increased expression of p-AKT1 was associated with decreased patient survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. zfeizhu@aliyun.com.

ABSTRACT

Background: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).

Methods: Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).

Results: p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.

Conclusion: Activation of AKT1 was associated with poor prognosis in ESCC.

No MeSH data available.


Related in: MedlinePlus