Immunohistochemical expression of the oncogenic molecules active Stat3 and survivin in benign and malignant salivary gland tumors.
OBJECTIVE
Signal transducer and activator of transcription 3 (Stat3) and survivin have been shown to exert oncogenic effects in various human neoplasms. The purpose of this study was to evaluate the expression of tyrosine phosphorylated (active) Stat3 and survivin in various benign and malignant salivary gland tumors (SGTs).


METHODS
Eighty-six SGTs (65 malignant and 21 benign tumors of various histopathologic subtypes) were immunohistochemically stained with antisurvivin or anti-phosphorylated tyrosine-705 (p-tyr) Stat3 antibodies. Immunohistochemical reactivity was graded in a semiquantitative manner; a combined score of immunohistochemical positivity (0-6) was calculated for each tumor by adding the individual scores for percentage of tumor cells (0-3) and intensity of staining (0-3).


RESULTS
Survivin was immunohistochemically detected in all studied benign and malignant SGTs; p-tyr Stat3 was also detected in the majority (91%) of SGTs. The average combined scores for survivin and p-tyr Stat3 immunohistochemical expression in the studied malignant SGTs was 4.40 and 3.35, respectively; the corresponding combined scores for survivin and p-tyr Stat3 in the studied benign SGTs were 4.37 and 3.22, respectively. No statistically significant differences (P > .05) in p-tyr Stat3 or survivin expression were detected between the benign and malignant groups, or among the various examined histopathologic subtypes of SGTs. In contrast, normal salivary gland tissues revealed only weak and focal survivin or p-tyr Stat3 immunoreactivity, mainly localized to ductal and mucous cells.


CONCLUSIONS
Our data indicate an almost universal expression of activated Stat3 and survivin in benign and malignant SGTs. Considering the well established proliferative and antiapoptotic properties of these molecules and their functional interrelationship, selective targeting techniques against Stat3 and/or survivin may represent promising therapeutic strategies against neoplasms of salivary gland origin.
Nikitakis
Nikolaos G
NG
Department of Oral Pathology and Medicine, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece. nnikitakis1@yahoo.com
Scheper
Mark A
MA
Papanikolaou
Vasileios S
VS
Sklavounou
Alexandra
A
Sauk
John J
JJ
D002277:Carcinoma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012466:Salivary Gland Diseases / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000077022:Survivin; D014018:Tissue Distribution
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D050796:STAT3 Transcription Factor; D000077022:Survivin