High Expression of p62 Protein Is Associated with Poor Prognosis and Aggressive Phenotypes in Endometrial Cancer

Reiko Iwadate, Jun Inoue, Hitoshi Tsuda, Masashi Takano, Kenichi Furuya, Akira Hirasawa, Daisuke Aoki, Johji Inazawa

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

High expression of SQSTM1/p62 (p62) protein, which functions as a hub of oncogenic signaling pathways, has been detected in several human cancers. However, the clinicopathological and functional contribution of p62 expression is largely unknown in endometrial cancers (ECs). In this study, we assessed the expression status of p62 in primary ECs (n = 194) by immunohistochemistry and analyzed its clinical significance. Although p62 was expressed in the cytoplasm and/or nucleus in primary ECs, we observed that an expression subtype, high expression of cytoplasmic p62 but low expression of nuclear p62 (cytoplasmHigh/nucleusLow), significantly correlated with nonendometrioid types (P = 0.002), high grade (P < 0.001), deep myometrial invasion (P = 0.025), vascular invasion (P = 0.012), and poor prognosis (P < 0.001), and may be an independent prognostic marker of ECs (P = 0.011). Furthermore, RNA interference-mediated inhibition of p62 expression in the HEC-1A EC cell line led to the reduction of invasiveness and resistance to oxidative stress in vitro, as well as the suppression of in vivo tumor growth in an orthotopic mouse model of ECs. High expression of cytoplasmic p62 is a novel prognostic biomarker of ECs, and excess p62 expression may functionally contribute to the acquirement of malignant phenotypes in EC cells.

Original languageEnglish
Pages (from-to)2523-2533
Number of pages11
JournalAmerican Journal of Pathology
Volume185
Issue number9
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

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Endometrial Neoplasms
Phenotype
Proteins
RNA Interference
Blood Vessels
Neoplasms
Cytoplasm
Oxidative Stress
Biomarkers
Immunohistochemistry
Cell Line
Growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

High Expression of p62 Protein Is Associated with Poor Prognosis and Aggressive Phenotypes in Endometrial Cancer. / Iwadate, Reiko; Inoue, Jun; Tsuda, Hitoshi; Takano, Masashi; Furuya, Kenichi; Hirasawa, Akira; Aoki, Daisuke; Inazawa, Johji.

In: American Journal of Pathology, Vol. 185, No. 9, 01.01.2015, p. 2523-2533.

Research output: Contribution to journalArticle

Iwadate, Reiko ; Inoue, Jun ; Tsuda, Hitoshi ; Takano, Masashi ; Furuya, Kenichi ; Hirasawa, Akira ; Aoki, Daisuke ; Inazawa, Johji. / High Expression of p62 Protein Is Associated with Poor Prognosis and Aggressive Phenotypes in Endometrial Cancer. In: American Journal of Pathology. 2015 ; Vol. 185, No. 9. pp. 2523-2533.
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