Clinicopathological Study On Lung Adenocarcinoma With BAC Feature

Objective:To investigate the clinicopathological characteristics of adenocarcinoma with BAC feature (adenocarcinoma mixed subtype, ADCM), compare it with BAC (bronchioloalveolar carcinoma, BAC) and adenocarcinoma without BAC feature (ADC) in morphological, molecular characteristics, and factors related to prognosis.Methods:1) All cases of lung cancer were collected from the archives of the Department of Pathology, Chinese PLA General Hospital from the year2004to2006. Adenocarcinomas of T1N0M0were rediagnosed based on the2004WHO classification of lung tumors. All cases of BAC and ADCM were taken into the study, and20cases of adenocarcinomas without BAC feature were chosen randomly as control group. Follow up was made.2) Morphological characteristics of ADCM were observed, and measurement of the central invasion were performed.3) EGFR gene mutations of exons19and21were detected by DNA sequencing.4) The immunohistochemistry was applied on tumor tissue microarray to test the expression of different molecular markers: Ki-67, PCNA, VEGF, MUC1, P21, P27, P-STAT3, P-AKT, Caveolin-1, EGFR.Results:1)139lung adenocarcinomas of T1N0M0were collected, of which22cases of BAC and51cases of ADCM with central invasion or fibrosis were confirmed.20cases of ADC without BAC feature or mucinous material were chosen as the control group. The time of follow-up was49-81months.2) The four-year survival rate of BAC was95.5%and the BAC of T<2cm was100%(13/13). One case (1/9) of BAC of T>2cm was dead. The four-year survival rate of ADCM was76.0%, T>2cm and T<2cm were75.8%and76.5%respectively. The four-year survival rate of ADC was40%. There was statistical significant difference in survival rate between three groups.(P<0.001).3) In the ADCM group, the central invasion usually presented structures of tubular, solid or clusters of a few cells. Some cases presented central fibrosis and desmoplastic reaction. The four-year survival rate of ADCM with central invasion≥10mm and<10mm were 53.8%and100%respectively, being significant different (P=0.001). The ADCM with invasion≥10mm showed statistical significant difference compared with ADC (P=0.01).4) Of91cases,28cases presented EGFR mutation of exons of19and21and the mutation rate was30.8%. The muation rate of nonsmokers (36.8%) was higher than smokers (13.0%)(P=0.033). EGFR mutation was not related to the tumor histology, gender and age.5) The expression of Ki-67, PCNA and EGFR showed statistical significant difference betwen the3groups (P<0.05). Patients with higher expression of EGFR and P21had worse outcome in comparison to lower expression (P<0.05). There was no relationship between EGFR mutation and EGFR protein expression (P=0.136). There was a higher expression of P21in the smokers than nonsmokers (P=0.025). The higher expression of P-AKT was accompanied with higher expression of MUC1(Spearman’s rank correlation coefficient0.228) and higher expression of P27was accompanied with lower expression of P-AKT (Spearman’s rank correlation coefficient=-0.275).Conclusions:1) The adenocarcinomas with BAC features with invasion<10mm show similar good outcomes with BAC.2) The adenocarcinomas with BAC features with invasion≥10mm have better outcomes than adenocarcinomas without BAC feature in the same clinical stage.3) The diagnosis of BAC with a diameter>2cm should be based on sufficient sampling.4) The muation rate of EGFR of nonsmokers is higher than smokers.5) The higher expression of Ki-67, PCNA, EGFR and P21are related to bad outcomes. The expression of P21of the nuclear in nonsmokers is higher than smokers.6) The higher expression of P-AKT was accompanied with higher expression of MUC1and higher expression of P27was accompanied with lower expression of P-AKT.