In the present study, we report cases of two synchronous lung adenocarcinomas composed of two distinct pathological subtypes with different EGFR gene mutations: a homozygous deletion in exon 19 of the papillary adenocarcinoma subtype and a point mutation of L858R in exon 21 of the tubular adenocarcinoma.
Papillary adenocarcinoma strongly correlated with EGFR mutation (P<0.001) and gene profile Cluster 1 (P=0.006) with weaker correlations with low grade (P=0.038) and favorable behavior in Stage 1 patients (P=0.047).
We studied the roles of FKHRL1 in both cisplatin-resistant Caov-3 (a papillary adenocarcinoma cell line) and cisplatin-sensitive A2780 human ovarian cancer cell lines.
PAR-2 expression occurred more frequently in papillary adenocarcinoma (15 of 16 patients, 94%) than in non-papillary types (20 of 42 patients, 48%, p=0.005).
Mutations of beta-catenin were more frequent in ampullary and gallbladder carcinomas than in bile duct carcinomas (P = 0.04) and in papillary adenocarcinomas than other histological types of carcinomas (P = 0.02).
C-myc gene amplification was found in the FU-OV-1 cells, and the xenografts, as well as in only the primary tumor of FU-OV-1 out of the four primary serous papillary adenocarcinomas.
C-erbB-2 was found more often in advanced cancers (P < 0.05), papillary adenocarcinoma (P < 0.01), nonscirrhous cancer (P < 0.05), and cancers with liver metastasis (P < 0.01).
The results imply that LOH occurs first in papillary adenocarcinoma followed by a p53 mutation during the transition from papillary adenocarcinoma to undifferentiated carcinoma.