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High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer.

Iwadate R, Inoue J, Tsuda H, Takano M, Furuya K, Hirasawa A, Aoki D, Inazawa J - Acta Histochem Cytochem (2014)

Bottom Line: High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers.However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC).Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Medical and Dental Science, Tokyo Medical and Dental University , Tokyo, Japan ; Department of Obstetrics and Gynecology, School of Medicine, Keio University , Tokyo, Japan.

ABSTRACT
High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary EOCs, and an expression subtype (Cyto(High)/Nuc(Low)), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto(High)/Nuc(Low) subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.

No MeSH data available.


Related in: MedlinePlus

Prognostic implication of the p62 expression status in epithelial ovarian cancer. A. Overall survival curves of all 266 patients with epithelial ovarian cancer (EOC) according to the expression level of cytoplasmic p62. This figure shows survival curves for 42 patients with high cytoplasmic p62-expressing tumors and for 224 patients with low cytoplasmic p62-expressing tumors. The two curves differ significantly. B. Overall survival curves of all 266 patients with EOC according to the p62 expression subtypes. This figure shows the survival curves for 38 patients with Type-D tumors (high expression of cytoplasmic p62 and low expression of nuclear p62; CytoHigh/NucLow) and for 228 patients with Type-A, -B, or -C tumors (CytoLow/NucLow, CytoLow/NucHigh, or CytoHigh/NucHigh, respectively). The two curves differ significantly. C. Overall survival curves of 107 patients with serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 30 patients with Type-D tumors and 77 patients with Type-A, -B, or -C tumors. The two curves differ significantly. D. Overall survival curves of 65 patients with high-grade serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 20 patients with Type-D tumors and 45 patients with Type-A, -B, or -C tumors. The two curves differ significantly.
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Figure 2: Prognostic implication of the p62 expression status in epithelial ovarian cancer. A. Overall survival curves of all 266 patients with epithelial ovarian cancer (EOC) according to the expression level of cytoplasmic p62. This figure shows survival curves for 42 patients with high cytoplasmic p62-expressing tumors and for 224 patients with low cytoplasmic p62-expressing tumors. The two curves differ significantly. B. Overall survival curves of all 266 patients with EOC according to the p62 expression subtypes. This figure shows the survival curves for 38 patients with Type-D tumors (high expression of cytoplasmic p62 and low expression of nuclear p62; CytoHigh/NucLow) and for 228 patients with Type-A, -B, or -C tumors (CytoLow/NucLow, CytoLow/NucHigh, or CytoHigh/NucHigh, respectively). The two curves differ significantly. C. Overall survival curves of 107 patients with serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 30 patients with Type-D tumors and 77 patients with Type-A, -B, or -C tumors. The two curves differ significantly. D. Overall survival curves of 65 patients with high-grade serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 20 patients with Type-D tumors and 45 patients with Type-A, -B, or -C tumors. The two curves differ significantly.

Mentions: To examine the clinicopathological and prognostic implications of p62 expression status in EOC, we performed the chi-square or Fisher’s exact test, as appropriate. High expression of cytoplasmic p62 and the Type-D (CytoHigh/NucLow) expression subtype were significantly associated with aggressive phenotypes, including serous histology (P=1.32×10−6 and P=1.46×10−7, respectively), advanced FIGO stage (P=7.85×10−3 and P=4.99×10−3, respectively), and presence of residual tumor (P=7.14×10−4 and P=3.74×10−4, respectively) (Table 1). Overall survival time of EOC patients was significantly shorter in the high cytoplasmic p62 expression group compared with the group with low expression (P=9.13×10−3, Fig. 2A) or in the group with the expression subtype of Type-D compared with the group with other subtypes (P=1.30×10−2, Fig. 2B).


High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer.

Iwadate R, Inoue J, Tsuda H, Takano M, Furuya K, Hirasawa A, Aoki D, Inazawa J - Acta Histochem Cytochem (2014)

Prognostic implication of the p62 expression status in epithelial ovarian cancer. A. Overall survival curves of all 266 patients with epithelial ovarian cancer (EOC) according to the expression level of cytoplasmic p62. This figure shows survival curves for 42 patients with high cytoplasmic p62-expressing tumors and for 224 patients with low cytoplasmic p62-expressing tumors. The two curves differ significantly. B. Overall survival curves of all 266 patients with EOC according to the p62 expression subtypes. This figure shows the survival curves for 38 patients with Type-D tumors (high expression of cytoplasmic p62 and low expression of nuclear p62; CytoHigh/NucLow) and for 228 patients with Type-A, -B, or -C tumors (CytoLow/NucLow, CytoLow/NucHigh, or CytoHigh/NucHigh, respectively). The two curves differ significantly. C. Overall survival curves of 107 patients with serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 30 patients with Type-D tumors and 77 patients with Type-A, -B, or -C tumors. The two curves differ significantly. D. Overall survival curves of 65 patients with high-grade serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 20 patients with Type-D tumors and 45 patients with Type-A, -B, or -C tumors. The two curves differ significantly.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: Prognostic implication of the p62 expression status in epithelial ovarian cancer. A. Overall survival curves of all 266 patients with epithelial ovarian cancer (EOC) according to the expression level of cytoplasmic p62. This figure shows survival curves for 42 patients with high cytoplasmic p62-expressing tumors and for 224 patients with low cytoplasmic p62-expressing tumors. The two curves differ significantly. B. Overall survival curves of all 266 patients with EOC according to the p62 expression subtypes. This figure shows the survival curves for 38 patients with Type-D tumors (high expression of cytoplasmic p62 and low expression of nuclear p62; CytoHigh/NucLow) and for 228 patients with Type-A, -B, or -C tumors (CytoLow/NucLow, CytoLow/NucHigh, or CytoHigh/NucHigh, respectively). The two curves differ significantly. C. Overall survival curves of 107 patients with serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 30 patients with Type-D tumors and 77 patients with Type-A, -B, or -C tumors. The two curves differ significantly. D. Overall survival curves of 65 patients with high-grade serous carcinoma according to the p62 expression subtypes. This figure shows the survival curves for 20 patients with Type-D tumors and 45 patients with Type-A, -B, or -C tumors. The two curves differ significantly.
Mentions: To examine the clinicopathological and prognostic implications of p62 expression status in EOC, we performed the chi-square or Fisher’s exact test, as appropriate. High expression of cytoplasmic p62 and the Type-D (CytoHigh/NucLow) expression subtype were significantly associated with aggressive phenotypes, including serous histology (P=1.32×10−6 and P=1.46×10−7, respectively), advanced FIGO stage (P=7.85×10−3 and P=4.99×10−3, respectively), and presence of residual tumor (P=7.14×10−4 and P=3.74×10−4, respectively) (Table 1). Overall survival time of EOC patients was significantly shorter in the high cytoplasmic p62 expression group compared with the group with low expression (P=9.13×10−3, Fig. 2A) or in the group with the expression subtype of Type-D compared with the group with other subtypes (P=1.30×10−2, Fig. 2B).

Bottom Line: High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers.However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC).Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Medical and Dental Science, Tokyo Medical and Dental University , Tokyo, Japan ; Department of Obstetrics and Gynecology, School of Medicine, Keio University , Tokyo, Japan.

ABSTRACT
High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary EOCs, and an expression subtype (Cyto(High)/Nuc(Low)), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto(High)/Nuc(Low) subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.

No MeSH data available.


Related in: MedlinePlus