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. 2009 Sep 15;101(6):967-72.
doi: 10.1038/sj.bjc.6605212. Epub 2009 Jul 28.

Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma

Affiliations

Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma

S Takemoto et al. Br J Cancer. .

Abstract

Background: Stat3 is a member of the Janus-activated kinase/STAT signalling pathway. It normally resides in the cytoplasm and can be activated through phosphorylation. Activated Stat3 (p-Stat3) translocates to the nucleus to activate the transcription of several molecules involved in cell survival and proliferation. The constitutive activation of Stat3 has been shown in various types of malignancies, and its expression has been reported to indicate a poor prognosis. However, the correlation between the constitutive activation of Stat3 and the prognosis of cervical cancer patients has not been reported.

Methods: The immunohistochemical analysis of p-Stat3 expression was performed on tissues from 125 cervical squamous-cell carcinoma patients who underwent extended hysterectomy and pelvic lymphadenectomy, and the association of p-Stat3 expression with several clinicopathological factors and survival was investigated.

Results: Positive p-Stat3 expression was observed in 71 of 125 (56.8%) cases and was significantly correlated with lymph node metastasis, lymph vascular space invasion, and large tumour diameter (>4 cm) by Fisher's exact test. Kaplan-Meier survival analysis showed that p-Stat3 expression was statistically indicative of a poor prognosis for overall survival (P=0.006) and disease-free survival (P=0.010) by log-rank test.

Conclusion: These data showed that p-Stat3 expression in cervical cancer acts as a predictor of poor prognosis.

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Figures

Figure 1
Figure 1
Immunoexpression of p-Stat3 in cervical cancer specimen (A), and normal cervical tissue (B). Only tumour cell nuclei were stained.
Figure 2
Figure 2
Correlation between the number of metastatic lymph nodes and p-Stat3 expression. The percentages of ‘++,’ ‘+,’ and negative p-Stat3 expression in each group are plotted.
Figure 3
Figure 3
Kaplan–Meier analysis of overall survival (A) and disease-free survival (B) after extended hysterectomy for p-Stat3-positive or p-Stat3-negative immunostaining.
Figure 4
Figure 4
Expression of Bcl-xL, VEGF, and p-Stat3 in cervical cancer cell line and the effect of Stat3 siRNA (A). Relative expression level standardised by β-actin expression level is indicated (B). The expression levels of both Bcl-xL and VEGF with Stat3 siRNA were more reduced than that with No Targeting siRNA (NT siRNA).

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