Accounts for approximately 30% of lung cancers in US annually, and 1 million persons worldwide each year.
Malignant epithelial tumors with glandular differentiation.
Adenocarcinoma is the most frequent type occurring in non-smokers and is usually found in the periphery of the lung and starts in mucus secreting cells.
Air pollution is linked to the risk of adenocarcinoma.
Adenocarcinomas can also occur centrally, and in a multifocal fashion or involve an entire lobe.
Subdivide into acinar, papillary, bronchioloalveolar, solid adenocarcinoma with mucin production, and mixed pattern-type.
Tumors are derived from alveolar, bronchial, or bronchiolar epithelial cells.
About 80% of adenocarcinomas demonstrate 2 or more histologic patterns
Atypical adenomatous hyperplasia can be a potential precursor of nonmucinous bronchioloalveolar carcinoma.
Adenocarcinomas metastasize primarily via lymphatic and hematogenous routes.
Approximately 20% of patients have distant metastasis at the time of diagnosis.
Most common sites of metastases including brain, bone, adrenal glands, and liver.
Higher than 50% frequency of actionable oncogenic drivers.
Guidelines recommend testing for EGFR mutations and ALK fusions in all patients with advanced adenocarcinoma regardless of gender, race, smoking history or other clinical factors.
Most lesions are thyroid transcription factor one (TTF1) positive.
Cytokeratin 7 and mucin staining are recommended markers for adenocarcinoma.
Mucinous bronchoalveolar carcinoma tumors from bronchial mucinous cells are generally TTF-1 negative and CK 20 positive.
Mucinous adenocarcinomas, are often multicentric, and are typically KRAS-mutation positive and EGFR-mutation negative.
Specific gene markers for AC of the lung include: ABCC3, CLDN3, DPP4, MUC3B, MUC5B, NTRK2, SPINK1, and TJP3.
ABCC3 is upregulated early in the disease.
CLDN3 and TJP3 are involved in tight junction, and are found preferentially expressed in adenocarcinoma of the lung.
DPP4 functions as her tumor suppressor gene, and its down-regulation may result in progression of cancer.
MUC3B and MUC5B are in the family of mucin genes that are important for tumor invasion and metastases.
About 5% of lung adenocarcinomas harbor the onchogenic fusion of EMLA4-ALK which is more prevalent in never or light smokers with tumors generally in younger patients with tumors that are wild type for EGFR and KRAS.
Over half of all cases can be to find by known genetic abnormalities or oncogenic drivers: most commonly activated mutations of KRAS and epidermal growth factor receptor, mutant BRAF and fusion oncogenes involving anaplastic lymphoma kinase (ALK).
KRAS mutations seen about 15-30% of patients with adenocarcinomas of the lung, more commonly in smokers.
KRAS mutations have been found to be mutually exclusive with EGFR mutations and ALK rearrangements.
ROS1 is a receptor tyrosine kinase of the insulin receptor family and the frequency of the ROS 1 rearrangement ranges from 0.9-1.7% in unselected non-small cell cancer patients.
ROS1 Rearrangement typically occurs in young never smokers who have adenocarcinoma, with a tendency toward higher grade.
Activation of oncogenic kinases such as epidermal growth factor receptor or anaplastic lymphoma kinase can lead to tumor dependent cells on activated kinase and sensitivity to the corresponding kinase inhibitor.
EGFR mutations in lung cancer account for 40% of adenocarcinomas of the lung in East Asians and about 15% in Caucasians and African Americans.
Most patients with adenocarcinoma of the lung with EGFR mutations are non-smokers or light smokers, and more likely to be female and Asian.
Check point inhibition is in ineffective therapy for patients with EGFR mutant lung cancer disease.
Front-line pemetrexed and platinum superior to gemcitabine and platinum, with superior efficacy and improved side effects.
Patients with activating mutations in the epidermal growth factor receptor (EGFR)domain or EML4-ALK translocation benefit from first-line treatment with erlotinib or crizotinib, respectively.
The LUX-Lung 3 study involved 345 patients with stage 3/4 lung adenocarcinoma that had tested positive for EGFR mutations who had not previously received chemotherapy.
In the LUX-Lung study patients were randomized in a 2:1 ratio to receive afatinib 40 mg daily or standard chemotherapy with cisplatin 75 mg/m² and pemetrexed 500 mg/m² intravenously every 21 days for up to 6 cycles: Median progression-free survival was better with afatinib than with chemotherapy (11.1 vs 6.9 months; hazard ratio, 0.58; P = .0004).