Changes in the epidermal growth factor receptor (<i>EGFR</i>) gene, Kirsten rat sarcoma viral oncogene (<i>KRAS</i>), v-Raf murine sarcoma viral oncogene homolog B (<i>BRAF</i>), gene encoding neurofibromin (<i>NF1</i>), anaplastic lymphoma kinase (<i>ALK</i>) and <i>ROS1</i> are the main genes that suffer alterations in the tumors of patients with ADC.
Thus, a major issue of current research is to define the morphological and immunophenotypic features of lung ALK-rearranged adenocarcinomas to improve the selection of tumors suitable for molecular genotyping.
Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma).
Fifteen ALK fluorescence in-situ hybridization (FISH) rearranged and 19 non-ALK FISH rearranged adenocarcinomas were collected retrospectively based on availability of tissue from a matched metastatic site.
When analyzed as either a continuous or a dichotomous variable, the mean number of tumor cells expressing PD-L1 (<i>p</i> = 0.012) and the percentage of tumor cells expressing PD-L1 were higher in <i>ALK</i>-positive ADC than in <i>EGFR-mutated</i> ADC or WT (non-<i>EGFR</i>-mutated and non-<i>KRAS</i>-mutated) NSCLC.
In conclusion, our findings indicate that optimized IHC using the D5F3 antibody provides a reliable and inexpensive test for identification of ALK-positive adenocarcinomas.
Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib.
Three biomarker-specified groups of advanced lung adenocarcinomas can now be defined, each paired with a specific palliative first-line systemic therapy of proven clinical benefit: (1) EGFR/ALK/ROS1-affected adenocarcinoma paired with a matched tyrosine kinase inhibitor (∼20% of cases), (2) PD-L1-enriched adenocarcinoma (TPS ≥50%) paired with anti-PD-1 pembrolizumab (∼30% of cases), and (3) biomarker-negative (i.e., EGFR/ALK/ROS1/PD-L1-negative) adenocarcinoma paired with platinum doublet chemotherapy with or without bevacizumab (∼50% of cases).
The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area: impact of smoking.
Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma.
The overall analyses revealed that positive PD-L1 expression had a significant relationship with KRAS status (RR = 1.26; 95% CI, 1.06-1.50, P = 0.010), but no correlation with clinical characteristics (gender, smoking status, histological types), driver gene status (EGFR, ALK) and overall survival (OS): male versus female (RR = 1.16; 95% CI, 0.95-1.42; P = 0.15), never smoking versus former/current smoking (RR = 0.79; 95% CI, 0.56-1.11; P = 0.17), adenocarcinoma versus non-adenocarcinoma (RR = 0.94; 95% CI, 0.63-1.41; P = 0.77), EGFR mutation versus EGFR wild type (RR = 0.74; 95% CI, 0.52-1.06; P = 0.10), ALK positive versus ALK negative (RR = 1.02; 95% CI, 0.75-1.38; P = 0.91), OS of positive PD-L1 expression versus that of negative PD-L1 expression (HR = 1.31, 95% CI, 0.90-1.90; P = 0.15), respectively.
We concluded that PIK3CA mutations and ALK rearrangement occur also in PAEDs, while NRAS mutations might be a very rare event similarly to pulmonary adenocarcinomas of conventional type.
The histopathological and immunohistochemical features of this particular tumor highlighting the overlapping criteria between lung adenocarcinomas and rare ALK-rearranged squamous cell lung carcinomas could also be relevant to extend ALK screening to tumors with intermediate phenotypes between squamous cell carcinomas and adenocarcinomas and/or arising in non-smokers.
ALK gene rearrangements are identified in 2-5 % of all non-small cell lung cancer and are more common in lifetime non-smokers with adenocarcinoma, but the prevalence of ALK rearrangements is not as well characterized in long-term ex-smokers (quit >10 years prior to diagnosis).
Guidelines recommend that EGFR and ALK tests are carried out in parallel on all confirmed and potential adenocarcinomas, and this is more efficient in terms of tissue usage and testing turnaround time for both of these actionable gene alterations.