Pulmonary adenocarcinoma with a micropapillary pattern: a clinicopathological, immunophenotypic and molecular analysis.

Aims: To investigate the clinicopathological and molecular characteristics, immunohistochemical profile and prognosis of pulmonary adenocarcinoma with a micropapillary pattern (MPPAC). Methods and results: Eight hundred and eighty-six pulmonary adenocarcinomas were divided into two groups: micropapillary pattern (MPP)-positive (>= 1% MPP) (n = 246) and MPP-negative (n = 640), and clinicopathological characteristics were analysed. Of these, 66 cases with extensive MPP (MPP 50%) were studied by immunohistochemistry for several markers, and mutational analysis of K-ras and epidermal growth factor receptor (EGFR) with the Scorpion Amplification Refractory Mutation System. Smoking, TNM stage, lymph node metastasis, lymphatic invasion, venous invasion, pleural invasion and differentiation grade were significantly associated with the prognosis of MPPAC (P < 0.05). Immunohistochemically, the positive rate in the MPP-positive group was 100% for E-cadherin, 100% for beta-catenin, 93.9% for Muc-1, 57.6% for EGFR, 37.9% for p53, and 95.5% for Ki67. No differences were identified between MPP and non-MPP tissue within the same tumour with regard to K-ras and EGFR mutations. The 5-year survival rates of patients were significantly different between the MPP-positive group and the MPP-negative group (P = 0.005). By multivariate analysis, a MPP was an independent prognostic factor for lung adenocarcinomas. Conclusions: MPP represents a distinct histopathological variant with biological and prognostic significance.