| Background and purpose:To investigate the roles of phosphatidylinositol-3-kinase (PI3K)/p-Akt signal transduction pathway involving in regulating cell proliferation, differentiation, apoptosis in pathogenesis of condyloma acuminatum (CA) and the genital squamous cell carcinoma (SCC). By analyzing the expression profiles of PI3K and its downstream p-Akt protein in CA and SCC, the significance of PI3K/p-Akt signaling in the pathogenesis of CA and genital SCC was discussed in this study.Methods:The EnVision two steps method of immunohistochemistry was used to detect the expression and distribution of PI3K and p-Akt protein in lesions of 30 cases of CA,30 cases with genital SCC and 20 cases of normal foreskin, the expression intensity of PI3K and p-Akt between each group and each layer was compared by rank sum test, respectively.Results:1. Expression of PI3K and p-Akt protein in normal foreskin tissues:1.1 PI3K protein located in the cytoplasm and showed yellow or yellowish-brown particles of deposition. The normal epidermal prickle cell layer, granular layer and stratum corneum did not express PI3K. Cells in the basal layer were shown positive or strong positive stained of PI3K. There was no positive stained cell in the dermis.1.2 P-Akt protein located in the cytoplasm and cell nucleus, and showed yellow or yellowish-brown particles of deposition. The normal epidermal prickle cell layer, granular layer and stratum corneum did not express p-Akt. Cells in the basal layer were shown positive or strong positive stained p-Akt. There was no positive cell in the dermis.2. Expression of PI3K and p-Akt protein in CA tissues:2.1 The horny layer of CA lesions did not express PI3K. The cytoplasm of granular layer, prickle cell layer, and basal cell layer could express varying degrees of PI3K, in which the prickle cell layer and granular layer could express PI3K stronger, while the basal layer could express PI3K relatively weaker. The vascular endothelial cell in the dermis showed also positive staining of PI3K.2.2 The prickle cell layer and granular layer of CA lesions did not express p-Akt, while the dendritic cells in the basal layer showed positive expression of p-Akt. There was no positive cell in the dermis.3. Expression of PI3K and p-Akt protein in the genital tissues of SCC:3.1 The tumor cell cytoplasm of the genital SCC-tissues was positive or strong positive expression of PI3K. The expression median of PI3K with high, medium, low differentiation of tumors was respectively 1,2 and 3. Due to the small samples of each group, the statistical analysis could not be conducted. However, based on the expression profile, it had shown that the poorer the tumor differentiation, the higher the PI3K expression intensity; the higher the degree of tumor differentiation, the lower the PI3K expression intensity. The expression intensities of PI3K in the central of SCC tumor mass and the surrounding basal layer were similar (the both medians were 2).The vascular endothelial cell in the dermis showed positive staining of PI3K3.2 The tumor cell cytoplasm and nucleus of the genital SCC tissues was weak positive or positive expression of p-Akt. The expression median of p-Akt with high, medium, low differentiation of tumors was respectively 1,1 and 2. Due to the small samples of each group, the statistical analysis could not be conducted. However, based on the expression profile, it had shown that the poorer the degree of tumor differentiation, the higher the p-Akt expression intensity; the higher the degree of tumor differentiation, the lower the p-Akt expression intensity. The expression intensities of p-Akt in the central of SCC tumor mass and the surrounding basal layer were similar.4. Comparison of the expression PI3K in CA, genital SCC and normal foreskin tissues:4.1 The expression median of PI3K in the basal cell layer of the normal foreskin, genital SCC, and CA was 2.5,2, and 1 with the medians of staining intensity, respectively. Comparison of the expression PI3K in the basal layer:the expression of PI3K in normal foreskin was significantly higher than that in CA (U= 4.680,p<0.05); There is no significance (U=0.864,P>0.05) of the expression of PI3K between normal foreskin and genital SCC lesions. The expression of PI3K in genital SCC was higher than that in CA (U=4.113,P<0.05).4.2 The expression intensities of PI3K in the granular layer, prickle cell layer of genital SCC, CA, and the normal foreskin were 2,2, and 0 with the medians of staining intensity, respectively. Comparison of the expression PI3K in the granular layer, prickle cell layer:the expression of PI3K in CA significantly higher than that in normal foreskin (U=5.728,p<0.05);Expression of PI3K in genital SCC was significantly higher than that in normal foreskin (U=5.723,p<0.05); the expression of PI3K between CA and genital SCC lesions has no significance (U=1.818,P>0.05).5. Comparison of the expression p-Akt in CA, genital SCC and normal foreskin tissues:5.1 The expression median of p-Akt in the basal cell layer of the normal foreskin, genital SCC, and CA was 2.5,1, and 1 with the medians of staining intensity, respectively. Comparison of the expression p-Akt in the basal layer:the expression of p-Akt in normal foreskin was significantly higher than that in CA(U=5.943,p<0.05); the expression of p-Akt in normal foreskin was significantly higher than that in genital SCC (U=3.502,p<0.05); the expression of p-Akt in genital SCC was higher than that in CA(U=3.043,p<0.05).5.2 The expression median of p-Akt in the granular layer, prickle cell layer of genital SCC, CA, and the normal foreskin was 1,0, and 0 with the medians of staining intensity, respectively. Comparison of the expression PI3K in the granular layer, prickle cell layer:Both CA and normal foreskin did not express p-Akt; the expression of p-Akt in genital SCC was higher than that in normal foreskin (U=5.388,p<0.05); the expression of p-Akt in genital SCC was higher than that in CA(U=6.263,p<0.05).Discussions and Conclusions:1.Compared with normal tissues, the expression of PI3K in CA tissues was up-regulated, but the expression of p-Akt was down-regulated. Whether the HPV virus gene or protein might be inhibited to the expression of p-Akt still remains to be confirmed by further studies.2.PI3K/Akt expression in genital SCC was up-regulated, and was related to tumor differentiation, suggesting that the signaling pathway was abnormal activation, and may be involved in the development of SCC.3. The activation of Akt was regulated not only by PI3K in the upstream, but also by other factors. Therefore, compared with genital SCC, the activation extent of the condyloma acuminate tissues was different in the PI3K/Akt signaling pathway. The different activation of the PI3K/Akt signaling pathway in CA might be affected by the high-risk and low-risk HPV stimulus,which remains to be confirmed by further studies. |
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