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Journal of the National Cancer Institute Advance Access originally published online on August 28, 2007
JNCI Journal of the National Cancer Institute 2007 99(17):1343-1344; doi:10.1093/jnci/djm091
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© The Author 2007. Published by Oxford University Press.

CORRESPONDENCE

Re: Decreased STAT1 Expression by Promoter Methylation in Squamous Cell Carcinogenesis

Thian-Sze Wong, Xiao-Bing Liu, Raymond Wai-Man Ng, William Ignance Wei, Anthony Po-Wing Yuen

Affiliation of authors: Department of Surgery, University of Hong Kong Medical Center, The University of Hong Kong, Hong Kong SAR China

Correspondence to: Thian-Sze Wong, Ph.D, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR China (e-mail: thiansze{at}graduate.hku.hk).

We read with great interest the article by Xi et al. (1), which reported that loss of signal transducers and activators of transcription 1 (STAT1) expression was a frequent event in head and neck squamous cell carcinoma (SCC). Xi et al. (1) also demonstrated that the loss of STAT1 expression was caused by promoter methylation. Based on their observation, we hypothesized that STAT1 expression is also reduced in tongue SCC. We first measured STAT1 mRNA levels in our patients. Instead of using normal buccal mucosa, we compared STAT1 expression levels of tongue SCC with paired normal tongue mucosa from the same patient. However, our results were contradictory to those observed by Xi et al. (1)—STAT1 transcript levels were higher in the SCC samples than in the normal samples (Fig. 1). To verify our observation, we performed immunohistochemical analysis of the normal tongue and tongue SCC samples (Fig. 2). In our cohort, STAT1 protein was overexpressed in 28 of 43 (65%) tongue SCC samples (Table 1). Using the Methylation-Specific Polymerase chain reaction primers and conditions described by Xi et al. (1), we found that STAT1 was unmethylated in all of the tongue SCC and paired normal tissues.


Figure 1
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  		Fig. 1. Signal transducers and activators of transcription 1 (STAT1) mRNA expression in tongue squamous cell carcinoma and corresponding paired normal tissues. Expression of STAT1 mRNA was evaluated using the comparative threshold cycle method (2–{Delta}CT) (2). STAT1 mRNA levels were quantified using TaqMan Gene Expression Assays specific for STAT1 mRNA (Applied Biosystems, Foster City, CA). Transcript levels of housekeeping gene 18S were used as endogenous control (TaqMan Endogenous Controls, Applied Biosystems). Boxes represent the interquartile range of STAT1 mRNA levels. The lines across the boxes represent the median values; circles represent the outlier. P = .004, Wilcoxon signed rank test, two-sided.

 


Figure 2
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  		Fig. 2. Immunohistochemical staining of signal transducers and activators of transcription 1 (STAT1) in tongue squamous cell carcinoma (SCC) and paired normal tissues. Formalin-fixed and paraffin-embedded tissue sections were stained using mouse monoclonal anti-STAT1 antibody (1:400, Cell Signaling, Beverly, MA) and developed using the DAKO Envision+ system (horseradish peroxidase, diaminobenzidine) (3). Immunohistochemical staining of STAT1 (brown) of normal tongue and SCC of tongue from two patients are shown.

 


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  		Table 1. Signal transducers and activators of transcription 1 (STAT1) protein expression in squamous cell carcinoma (SCC) of the tongue*

 
The variety of tumors that Xi et al. (1) used might have partly contributed to the differences in their results and ours. Xi et al. (1) used control tissues that were obtained from different individuals and from different regions of the head and neck. In our experience, STAT1 mRNA expression in tongue SCC varied greatly among individuals. In addition, STAT1 expression might vary by geographic region.

We suggest that STAT1 promoter methylation is not a consistent event in head and neck cancers. STAT1 promoter methylation was not observed in tongue SCC in our patients, and STAT1 expression was higher in SCC cells than in normal tongue epithelial cells. In-depth analysis is warranted to clarify the role of STAT1 in the development of head and neck cancer.

Funding

Research Grants Council, Hong Kong Special Administrative Region, China (7651/06M).

REFERENCES

(1) Xi S, Dyer KF, Kimak M, Zhang Q, Gooding WE, Chaillet JR, et al. Decreased STAT1 expression by promoter methylation in squamous cell carcinogenesis. J Natl Cancer Inst. (2006) 98:181–9.[Abstract/Free Full Text]

(2) Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (2001) 25:402–8.[CrossRef][ISI][Medline]

(3) El-Hashemite N, Kwiatkowski DJ. Interferon-gamma-Jak-Stat signaling in pulmonary lymphangioleiomyomatosis and renal angiomyolipoma: a potential therapeutic target. Am J Respir Cell Mol Biol (2005) 33:227–30.[Abstract/Free Full Text]


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This Article
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