β3 integrin immunohistochemistry as a method to predict sentinel lymph node status in patients with primary cutaneous melanoma.

Abstract

Integrins are heterodimeric proteins composed of noncovalently linked ɑ and β subunits which are essential for a wide range of normal physiology and also play prominent roles in cancer. Here we tested whether integrin expression in diagnostic skin biopsies is associated with sentinel lymph node (SLN) metastasis. We utilized a cohort of 854 consecutive patients with primary cutaneous melanoma to quantify the expression of β integrin subunits by reverse transcriptase quantitative PCR (RT-qPCR). In addition, we quantified the expression of β3 integrin by immunohistochemistry (IHC) in a subset of 271 patients by H score. Outcome of interest was SLN biopsy metastasis within 90days of melanoma diagnosis. Logistic regression analyses were used to develop models for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. β3 integrin expression quantified by IHC or RT-qPCR was associated with SLN metastasis. β1, β5, β6, and β8 integrin expression was not associated with SLN metastasis. The incremental gain in performance of a predictive model which included β3 integrin expression as quantified by IHC in combination with established clinicopathologic variables (Breslow depth and patient age) was limited. β3 integrin is the principal integrin subunit associated with sentinel lymph node biopsy (SLNb) metastasis in primary cutaneous melanoma. However, β3 integrin H score does not significantly improve models for the likelihood of SLN metastasis over Breslow depth and patient age.