Analysis of the occurrence and distribution of primary and recurrent basal cell carcinoma of head and neck coupled to the assessment of tumor microenvironment and Sonic hedgehog signaling

Often, basal cell carcinoma (BCC) displays local aggressiveness, and when developed in the head and neck presents with deep tissue invasion and recurrence. Previous studies have pointed out the necessity of systematic assessment of primary and recurrent BCC based on a better understanding of the biology and function of its microenvironment. Although hedgehog-dependent tumor cells signaling to the underlying stroma, and vice versa, have been demonstrated to be implicated in the pathogenesis of BCC, little is known about peculiarities of the tumor microenvironment and the above-mentioned signaling in the head and neck. The occurrence and distribution of 79 primary and recurrent BCCs developed in the head and neck region were estimated. The data were coupled with the immunohistochemical assessment of type IV collagen, laminin, alpha-smooth muscle actin (alpha-SMA), and Sonic hedgehog (Shh). The frequency of the mixed BCCs and the predominance of the nose and cheek region affection by primary and recurrent tumors were demonstrated. Furthermore, the increase of peritumoral and entire stromal alpha-SMA immunoreactivity in the mixed recurrent BCC was confirmed using statistics. We found the increase of strong levels of Shh immunoexpression in the aggressive variants of BCC - infiltrative, mixed, and micronodular. Surprisingly, we confirmed the upregulation of Shh paralleled by the downregulation of alpha-SMA immunoexpression in the superficial subtype of the tumor. Our results suggest the necessity of further studies assessing the nature of the tumor along with the peculiarities of signaling in BCCs of head and neck.