Abstract:

Ge Xinhong*, Tang Zhenzhen, Jiao Yaning, Wang Le, Yang Jing, Dong Lingdi, Hou Jingmei, Wu Hao, Yang Biao. *Department of Dermatology, General Hospital of Ningxia Medical University, Ningxia 750004, China Corresponding author: Ge Xinhong, Email: gexinhong.0101@163.com 【Abstract】 Objective To measure the expressions of phosphorylated ERK1/2 （p-ERK1/2）, p-JNK, p-p38 mitogen-activated protein kinase （p-p38 MAPK）, their upstream epidermal growth factor receptor （EGFR） and downstream transcription factor Elk-1 in actinic keratosis （AK） and cutaneous squamous cell carcinoma （SCC）. Methods Skin specimens were resected from the lesions of patients with AK, well-, moderately- and poorly-differentiated SCC and from normal skin of 30 healthy human controls. The number of skin specimens of AK and SCC at different degrees of differentiation was uniformly 30, with the total number of lesional specimens being 120. Both immunohistochemistry and Western blot were performed to measure the expressions of p-EGFR, p-ERK1/2, p-JNK, p-p38MAPK and p-Elk-1 in these specimens. Statistical analysis was carried out by using one-way analysis of variance and Pearson correlation analysis. Results The immunohistochemical study showed that p-EGFR expression was significantly higher in SCC than in AK and normal skin specimens （both P < 0.05）, but no significant difference was observed between AK and normal skin specimens. The expressions of p-ERK1/2, p-JNK, p-p38MAPK and p-Elk-1 were all significantly higher in SCC than in AK and normal skin specimens （all P < 0.05）, and higher in AK than in normal skin specimens （all P < 0.05）. The expressions of p-ERK1/2, p-JNK and p-p38MAPK in SCC increased with the decrease in differentiation degree of SCC （all P < 0.05）, while there was no statistical difference in the expressions of p-EGFR or p-Elk-1 between well- and moderately-differentiated SCC specimens. Western blot results were similar to the immunohistochemical results. The expression intensity of p-EGFR was positively correlated with that of p-ERK1/2, p-JNK and p-p38MAPK respectively in SCC （r = 0.843, 0.819, 0.902, respectively, all P < 0.01）, so was that of p-Elk-1 （r = 0.874, 0.843, 0.893, respectively, all P < 0.01）. The expression intensity of p-EGFR was only positively correlated with that of p-p38MAPK in AK （r = 0.707, P = 0.022）. Conclusions The expression levels of p-EGFR, p-ERK1/2, p-JNK, p-p38MAPK and p-Elk-1 in lesions are associated with the histological grade of SCC. The signal transduction pathways phosphorylated EGFR→ERK1/2, JNK and p38MAPK→Elk-1 may play a key role in the occurrence and development of AK and SCC.