EGF and neoplasm: The question why LRIG1 is upregulated in benign or differentiated (low-grade) tumor cannot clearly be answered from the present data, but it is conceivable to theorize that LRIG1 acts within a framework of a negative feedback loop, as previously shown by Gur et al. [17]; i.e., in response to the excessive EGF or EGFR stimulation which makes the cells abnormally proliferate, LRIG1 may overexpress to attenuate the abnormal proliferation to maintain the quiescence of the epithelium.