CCNE1 and invasive carcinoma: Early alterations include overexpression of cyclin D1, cyclin E and p53, whereas loss of retinoblastoma expression occurs late in the development of invasive carcinoma.25 We found that although reduced expression of MLH1, MSH2 and MGMT was not uncommon in invasive NSCLC, it was relatively rare in precursor lesions, with no reductions seen in the earliest histological abnormalities of metaplasia and dysplasia.