From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636).
To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations.
A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%).
In summary, mixed non-mucinous bronchioloalveolar carcinoma (BAC) or papillary components and papillary predominant adenocarcinoma showed a higher frequency of EGFR mutations than mucinous BAC components; Also, EGFR mutations were significantly more common in tumors with TITF-1 or SP-A expressions than in those without (p=0.002, p=0.026), especially the sensitivity of TITF-1 (96.9%) and the negative predictive value of TITF-1 (88.2%).
We assume that the LCNEC originated from the adenocarcinoma based on the fact that the patient was a non-smoking female, the tumor was located in the periphery, the tumor had a BAC component, and the same EGFR mutation was found in both the LCNEC and adenocarcinoma components.
The presence of prominent INCI (P = 0.036), papillary fragments (P = 0.041), and histologic features of BAC on paraffin block (P = 0.039) correlated with the presence of EGFR mutations.
In the tumors ≤2 cm in diameter, pSTAT3 expression in the central area was higher in preinvasive tumors than in invasive tumors (p=0.005). pSTAT3 was identified in the BAC component of 88% of the EGFR mutant (n=17) and 82% of the wild-type tumors (n=33).
Patients who had progressed during or after first-line chemotherapy were prospectively assigned to EGFR-TKI treatment as follows: (G1) EGFR mutation (n = 12); (G2) highly polysomic/amplified EGFR (n = 18); (G3) EGFR and/or pAKT positive (n = 41); (G4) adenocarcinoma/bronchoalveolar carcinoma and no smoking history (n = 15).
Epidermal growth factor receptor (EGFR) mutation has been known to be associated with adenocarcinoma with bronchioloalveolar carcinoma (BAC; lepidic) feature.
Patients with resectable stage I and II non-small cell lung cancer (NSCLC) enriched for the likelihood of EGFR mutation (≤ 15 pack-year cigarette smoking history and/or a component of bronchioloalveolar carcinoma) received preoperative gefitinib for 21 days.
It also includes the first proposed treatment paradigm that integrates both EGFR mutational status and the sub-histologies, mucinous and nonmucinous BAC.
Detailed pathologic examination showed significant genotype-phenotype correlations between EGFR mutations and presence of a bronchioloalveolar carcinoma component, a micropapillary pattern, and the hobnail cell type.
Upon alteration of the BAC/adenocarcinoma components, the EGFR tyrosine kinase inhibitor-untreated series, which had at least one episode of an EGFR-activating mutation, represented 3 potential hypotheses: no significant EGFR evolution for a single clone, genetic alterations from mutant to wild-type EGFR for multifocal lesions, or a switch from wild-type to mutant EGFR, leading to indeterminable cancer progression.
Frequency of EGFR and KRAS mutations in Japanese patients with lung adenocarcinoma with features of the mucinous subtype of bronchioloalveolar carcinoma.
EGFR amplification was seen in seven (6.25%) of 112 interpretable BAC and typically high-level with more than 10-20 EGFR copies per tumour cell (EGFR/centromere 7 ratio >3).
We conclude that characteristic histological features, i.e. the hobnail cell morphology and the presence of BAC component and MPP are good predictors of EGFR mutations in lung adenocarcinoma.
These mutational oncogenic differences could lead to different therapeutic responses: nonmucinous BAC has been found to be sensitive to EGFR tyrosine kinase inhibitors, while mucinous BAC might be more responsive to taxane-based chemotherapy.
We report a patient with a mixed adenocarcinoma of the lung that had different EGFR mutations in the papillary subtype, the acinar subtype, and the surrounding AAH and BAC areas.