Gkouveris I, Nikitakis N, Avgoustidis D, Karanikou M, Rassidakis G, Sklavounou A
Department of Oral Pathology and Medicine, Dental School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Oral and Maxillofacial Surgery, "Evaggelismos" Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Histol Histopathol. 2017 Oct;32(10):1065-1076. doi: 10.14670/HH-11-868. Epub 2017 Jan 16.
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 differentiation. Immunohistochemical assessment of the phosphorylated levels of STAT3(tyrosine/ serine), ERK1/2 and JNK was performed in 60 OSCC, including well, moderately and poorly differentiated tumors. Semiquantitative 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.
信号转导与转录激活因子3（STAT3）以及丝裂原活化蛋白激酶（MAPK），包括细胞外信号调节激酶（ERK）和应激活化蛋白激酶（JNK），已被证实与口腔鳞状细胞癌（OSCC）的发生发展有关。我们的目的是通过免疫组织化学方法评估OSCC中活化的STAT3、ERK1/2和JNK的水平，并研究这些分子之间以及它们与肿瘤分化程度之间可能存在的相关性。对60例OSCC进行了免疫组织化学评估，这些病例包括高分化、中分化和低分化肿瘤，检测了STAT3（酪氨酸/丝氨酸）、ERK1/2和JNK的磷酸化水平。采用半定量评分系统，通过计算免疫染色强度、阳性细胞百分比和综合评分来评估。统计学分析包括Fisher检验、Student's T检验和Kruskal-Wallis分析、Spearman相关系数和多因素逻辑回归分析。pSTAT3（酪氨酸）和pERK1/2的免疫组织化学水平在高分化和低分化肿瘤之间存在统计学显著差异，低分化肿瘤的平均百分比、强度和总分更高。另一方面，与低分化肿瘤相比，pJNK在中分化肿瘤中的强度水平在统计学上显著更高。pSTAT3（丝氨酸）免疫表达似乎与肿瘤分化无关。在不同分子之间，更显著的是，pERK1/2水平与pSTAT3（丝氨酸）、pSTAT3（酪氨酸）和pJNK表达呈统计学显著正相关。ERK1/2和STAT3的激活（通过酪氨酸而非丝氨酸磷酸化评估）可能导致OSCC中肿瘤分化程度降低，而JNK激活可能具有相反的作用，尽管可能不太明显。MAPK和STAT3水平之间的正相关可能表明存在直接的相互作用和/或由共同上游途径进行的调节。
