Sections were counterstained with haematoxylin. Magnification A (20×) and B (40×) This result suggests that activation of this important pathway is involved in the pathogenesis of non-melanoma skin cancer. Similar observations have been reported previously. In one study, 11 SCC and 17 BCC were stained for pAkt and both tumors showed expression of pAkt [41]. Another immunohistochemical study included 50 SCC and 20 BCC and found also a higher pAkt
expression in SCC than in BCC [42]. Finally in a recent report including 30 SSC and 31 BCC no significant difference regarding pAkt expression was detected between SCC and BCC even though all BCC showed positive signal for pAkt in immunohistochemistry [43]. Therefore, our immunohistochemical results confirm previous reports about the role of the PI3K ⁄Akt signaling pathway in Capmatinib cost the pathogenesis of non-melanoma skin cancer, including BCC. However, it GDC-941 was reported that Akt1 isoform may be down-regulated in human SCC, while Akt2 isoform is up-regulated in most cases [13]. This selleck compound increased phosphorylation of pAkt in NMSC may be caused by activating mutations of Akt2, but these mutations appear to be very infrequent events with no clear functional relevance [44–46]. On the contrary experimental evidences indicate that Akt2 up-regulation occurs mostly in the β-HPV/+ve tumor [13]. Therefore, the detected increased phosphorylation of pAkt
in our BCC may be also caused by beta-HPV induced activation of Akt2. Indeed Akt2 expression was detected in 14 out of 35 BCC (40%) and in particular in samples in which the presence of beta HPV was associated with an over expression of p16INK4a (Table 1 and Figure 3). HPV, p16INK4a, and Akt Many studies investigated the correlation between HPV infection and skin tumor pathogenesis but so
far HPV types with a putative increased malignant potential have been observed mostly only in SCC, in a few EV patients Glutamate dehydrogenase and in some cases of NMSC of immunosuppressed transplant recipients. Data on the relationship between BCC and HPV infection are still not consistent with a causative role. Nevertheless our data indicate an association between β-HPV and the expression of p16INK4a and Akt that are involved in cell cycle deregulation. The immunohistochemistry data showed the activation of Akt/PI3K pathway in BCC and literature data suggest that HPV can interact with this pathway by activating the isoform Akt2 [13, 42]. The simultaneously up-regulation of p16INK4a may reflect the interaction of E7 oncogene of β-HPV species 2 with pRb, with a mechanism similar to that already reported for α-HPV [16]. Indeed recent reports indicate that the E7 protein of β HPV may interact in vitro with pRb (Cornet I., personal communication) causing an elevation of p16INK4a expression. In particular we detected and defined the expression of p16INK4a as moderate with less that 30% positive keratinocytes or high with 30% or more positive cells.