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Biomarkers pS6 and pERK as Predictors of Skin Cancer Aggressiveness

Objectives: The role of elective parotidectomy and the extent of surgery for occult nodal metastasis in cutaneous squamous cell carcinoma (SCC) is controversial. We wanted to determine if the MEK/ERK pathway and pathologic features in the tumor could predict skin cancer aggressiveness and allow for preemptive treatment of occult metastasis. Methods: Retrospective experimental laboratory study and chart review. Specimens from basal cell carcinoma (BCC; n = 13), squamous cell carcinoma (SCC; N = 10), and SCC with parotid metastasis (n = 11) were analyzed by immunohistochemistry (IHC) for pERK (Thr202/Tyr204) and pS6 (Ser235/236) and scored by the study pathologist. Simple logistic regression analysis evaluated all subjects with previous resection of cSCC and parotidectomy (n = 13) for independent risk factors of disease aggressiveness. Results: Expression of pS6 increased in cSCC with parotid metastasis (P = .01) compared with other groups. BCCA and SCCA comparison showed an increase in pS6 expression in SCC (P < .01). There was no significant difference in pERK expression between groups. Factors associated with cSCC with nodal metastasis were previous skin positive margins (P = .03) and parotid perineural invasion (P = .04). Positive margins on primary lesions is an independent risk factor for deep lobe involvement (P = .03). Conclusions: Positive margins on primary skin lesions, perineural involvement of parotid specimens, and Biomarker pS6 appear to be predictors of aggressiveness in cSCC and should prompt increased monitoring or elective treatment. As pERK was not significantly activated, pS6 overexpression could indicate activation of the Akt/mTOR pathway.