Immunohistochemical expression of the oncogenic molecules active Stat3 and survivin in benign and malignant salivary gland tumors

Abstract

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 the tyrosine phosphorylated (active) Stat3 and survivin in various benign and malignant salivary gland tumors (SGTs). Study design Eighty-six SGTs (65 malignant and 21 benign tumors of various histopathologic subtypes) were immunohistochemically stained with anti-survivin or anti-phosphorylated tyrosine-705 (p-tyr) Stat3 antibodies. Immunohistochemical reactivity was graded in a semi-quantitative 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>0.05) in p-tyr Stat3 or survivin expression were detected between the benign and malignant groups, or among the various examined histopathological subtypes of SGTs. In contrast, normal salivary gland elements in the vicinity of the studied tumors 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 anti-apoptotic 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.

Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer

“…Nikitakis et al. 18 found no difference in the expression of survivin between malignant and benign salivary gland tumours. On the other hand, in a study of 29 benign salivary gland tumours by means of comparative genomic hybridization, Giefing et al.…”

“…Previous studies have shown that survivin is expressed during embryonic salivary gland development, 9 but only to a very low extent in normal adult salivary gland tissue 18 . Nikitakis et al.…”

“…Nikitakis et al. 18 have described survivin expression in normal salivary gland tissue, mainly localized to ductal cells. This might have been a methodical problem, as ductal cells are rich in mitochondria, which are known to cross‐react with biotin if not blocked during immunohistochemistry 20 .…”

“…However, they found no statistically significant differences in immunohistochemical survivin expression between benign and malignant salivary gland tumours, or among the various histopathological subtypes of SGC examined. 18 The aim of this study was to assess, for the first time to our knowledge, the expression and long-term prognostic value of the inhibitor of apoptosis protein survivin in AC and MEC of the major salivary glands.…”

Induction function of siRNA-mediated survivin gene silencing on nasopharyngeal carcinoma cell apoptosis

“…The survivin protein has 142 amino acids and a double function in inhibiting cell apoptosis and regulating cell division. Survivin gene expression is highly specific to tumor cells, and the protein is not expressed in most normal tissues (Xiang et al, 2006;Nikitakis et al, 2009), making survivin a target for cancer therapy. Currently, there are 2 treatment methods targeting survivin: antisense oligodeoxy nucleotide and RNAi.…”