ERK1/2, JNK and STAT3 activation and correlation with tumor differentiation in oral SCC

I. Gkouveris¹, N. Nikitakis¹, D. Avgoustidis², M. Karanikou³, G. Rassidakis³ and A. Sklavounou<sup>1

1</sup>Department of Oral Pathology and Medicine, Dental School, National and Kapodistrian University of Athens, ²Department of Oral and Maxillofacial Surgery, "Evaggelismos" Hospital, National and Kapodistrian University of Athens and ³First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

Offprint requests to: Dr. I. Gkouveris, Department of Oral Pathology and Medicine, Dental School National and Kapodistrian University of Ahtens, Greece. e-mail: igkouver@gmail.com

Summary. Signal transducer and activator of transcription 3 (STAT3) and mitogen activated protein kinases (MAPKs), including ERK and JNK, have been implicated in oral squamous cell carcinoma (OSCC) development and progression. Our purpose was to evaluate the levels of activated STAT3, ERK1/2 and JNK by immunohistochemistry in OSCC and to investigate possible correlations of these molecules with each other as well as with the degree of tumor differen-tiation. Immunohistochemical assessment of the phospho-rylated levels of STAT3(tyrosine/ serine), ERK1/2 and JNK was performed in 60 OSCC, including well, moderately and poorly differentiated tumors. Semi-quantitative scoring system was used, by calculating intensity of immunostaining, percentage of positive cells and combined scores. Statistics included Fisher's test, Student's T-Test and Kruskal-Wallis analysis, Spearman's correlation coefficient and multivariate logistic regression analyses. Immunohistochemical levels of both pSTAT3(tyr) and pERK1/2 showed statistically significant differences between well and poorly differentiated tumors with the latter receiving higher mean percentage, intensity and total scores. On the other hand, pJNK showed statistically significantly higher intensity levels in moderately compared to poorly differentiated tumors. pSTAT3(ser) immunoexpression did not appear to correlate with tumor differentiation. Between different molecules, more pronounced, pERK1/2 levels exhibited statistically significant positive correlation with pSTAT3(ser), pSTAT3(tyr) and pJNK expression. ERK1/2 and STAT3 activation (as assessed by tyrosine but not serine phosphorylation) could contribute to a less differentiated phenotype in OSCC, while JNK activation may have an opposite, although possibly less pronounced, effect. Positive correlations between MAPK and STAT3 levels may indicate a direct crosstalk and/or regulation by common upstream pathways. Histol Histopathol 32, 1065-1076 (2017)

Key words: MAPK, STAT3, Correlation, Tumor grade

DOI: 10.14670/HH-11-868