Decreased Expression of 14-3-3σ Is Associated with Advanced Disease in Human Epithelial Ovarian Cancer

Nagase

et al. 2013

Tohoku J. Exp. Med.

Self Cite

Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3σ gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3σ is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3σ expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3σ when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3σ and 22 (41.3%) had decreased 14-3-3σ staining. Decreased immunoreactivity for 14-3-3σ was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3σ expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3σ gene. These CpG islands were hypermethylated in 30% of 14-3-3σ-positive UPSC and 80% of 14-3-3σ-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3σ may be a predictor of poor prognosis in patients with UPSC.

Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Decreased Expression of 14-3-3<i>σ</i> Is Predictive of Poor Prognosis for Patients with Human Uterine Papillary Serous Carcinoma

Nagase

et al. 2013

Tohoku J. Exp. Med.

Self Cite

“…Loss of 14-3-3σ expression in association with hypermethylation has also been reported in several other cancers, including ovarian [8], hepatocellular [9], prostate [10], some lung [11], gastric [12] and endometrial carcinomas [13]. It is important to point out that this is not the only mechanism for 14-3-3σ down-regulation.…”

Section: Introductionmentioning

confidence: 87%

Regulation of 14-3-3σ expression in human thyroid carcinoma is epigenetically regulated by aberrant cytosine methylation

Lal¹,

Padmanabha²,

Provenzano³

et al. 2008

Cancer Letters

Increased 14-3-3σ expression has been observed by immunohistochemistry in papillary and anaplastic tumors, but not follicular thyroid cancers. 14-3-3σ mRNA expression and methylation status was examined in tumor cell lines and primary thyroid tissues using real-time RT-PCR, bisulfite sequencing and methylation-specific PCR. Most of the 27 CpG's in the gene's CpG island were methylated in normal thyroid, TPC-1, NPA, FTC-238 and 2-7, which did not express 14-3-3σ. In contrast, they were unmethylated in KAK-1 and anaplastic lines KAT4 and DRO-90. 14-3-3σ expression was not increased in thyroid carcinomas, the majority of which had a methylated CpG island. In addition, 5-aza-dC treatment increased 14-3-3σ expression in the FTC-238 and NPA cell lines, which had low baseline expression. We conclude 14-3-3σ expression in thyroid carcinomas is regulated by CpG island hypermethylation.

“…Seven different isoforms have been identified in mammalian cells, with each isoform having distinct tissue localization and function. Amongst the various 14-3-3 isoforms, 14-3-3 sigma is differentially expressed in cancers of breast, lung, prostate and ovary (9)(10)(11)(12). Qi et al (13) have shown elevated levels of beta, gamma, sigma and theta isoforms of 14-3-3 in human lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of 14-3-3 Zeta in Human Esophageal Cancer

et al. 2008

ABSTRACT:We recently found 14-3-3 zeta to be overexpressed in esophageal squamous cell carcinomas (ESCCs) by differential display. In the present study we determined the clinical significance of 14-3-3 zeta in esophageal tumorigenesis. Immunohistochemical analysis was carried out in 61 ESCCs, 33 dysplasia samples, 14 hyperplasia samples and 7 matched histologically normal esophageal tissues and correlated with clinicopathological parameters. Cytoplasmic expression of 14-3-3 zeta protein was observed in 95% of ESCCs; 63% of tumors also showed nuclear localization. All hyperplastic and dysplastic tissues distant from ESCCs as well as dysplastic endoscopic biopsies showed cytoplasmic immunopositivity for 14-3-3 zeta, while nuclear localization was observed in 58% of dysplasia and 36% of hyperplasia samples. Matched distant histologically normal epithelia either showed basal cytoplasmic expression of 14-3-3 zeta or no detectable nuclear expression of the protein. Interestingly, immunopositivity observed in normal esophageal tissues and early hyperplasia was confined to cytoplasm only, though significant nuclear expression was detected in dysplasia and ESCC. Immunoblotting and RT-PCR analyses further confirmed 14-3-3 zeta expression in dysplasia and ESCC. To our knowledge, this is the first report demonstrating overexpression of 14-3-3 zeta in esophageal hyperplasia, dysplasia and squamous cell carcinoma, suggesting that alteration in its expression occurs in early stages and is associated with esophageal tumorigenesis. (Int J Biol Markers 2008; 23: 231-7)