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):1344; doi:10.1093/jnci/djm093
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Response: Re: Decreased STAT1 Expression by Promoter Methylation in Squamous Cell Carcinogenesis
Affiliations of authors: The Eye and Ear Institute, Pittsburgh, PA 15213 (JRG); Department of Otolaryngology-Head and Neck Surgery (JC, IS) and Division of Plastic and Reconstructive Surgery (SM), Johns Hopkins Medical Institutions, Baltimore, MD
Correspondence to: Jennifer Rubin Grandis, MD, FACS, The Eye and Ear Institute, Rm 105, 200 Lothrop Street, Pittsburgh, PA 15213 (e-mail: jgrandis{at}pitt.edu).
We appreciate the opportunity to comment on the interesting findings of Wong et al. Their results indicate that regulation of signal transducers and activators of transcription 1 (STAT1) expression may be site specific in head and neck cancer, with increased expression being more common than loss of expression in tongue cancer. As noted by Wong et al., we used control normal mucosa samples that were derived from subjects without cancer, whereas they used normal mucosa adjacent to the tumor. We and others (1,2) have previously noted that this adjacent normal mucosa often contains genetic and epigenetic alterations that more closely resemble tumor tissue, including increased expression of STATs. Furthermore, we measured STAT1 protein expression using western blotting, whereas Wong et al. assessed mRNA expression using reverse transcription–polymerase chain reaction. Thus, determination of relative STAT1 levels may be influenced by both the nature of the comparative normal mucosa and the methods used to measure expression. It is also possible that the role of STAT1 loss or increased expression in head and neck cancer may be associated with the site of tumor origin. In addition, we agree with Wong et al. that interpatient variability and geographic distinctions may be important.
Of note, we have revisited the methylation status of the STAT1 promoter region: the original primer sets used for bisulfite sequencing analysis were designed in a manner that selectively amplifies methylated DNA species. Redesign of these primers to amplify this region in an unbiased manner after bisulfite treatment was performed, and a separate cohort of six primary head and neck cancers and six mucosal samples from subjects without cancer all demonstrated lack of promoter methylation. However, STAT1 expression in this new cohort was not assessed. Whether differences in primer design explain the differences in the findings of our study and those of Wong et al. is unknown. Collectively, these findings of STAT1 expression in head and neck cancers further underscore the heterogeneous nature of this malignancy.
REFERENCES
(1) Leong PL, Andrews GA, Johnson DE, Dyer KF, Xi S, Mai JC, et al. Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc Natl Acad Sci USA (2003) 100:4138–43.
(2) Xi S, Zhang Q, Gooding WE, Smithgall TE, Grandis JR. Constitutive activation of Stat5b contributes to carcinogenesis in vivo. Cancer Res (2003) 63:6763–71.
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