EGFRmutation and lobar location of lung adenocarcinoma

Abstract

The objective of this study was to investigate the associations among lung cancer location, and epidermal growth factor receptor (EGFR) mutation status. Treatment-naive, pathologically confirmed lung adenocarcinomas with tumor specimens available for genetic analysis were included from 2011 through 2014. Overall, 1771 patients with lung adenocarcinoma were included for analysis, after excluding those with carcinoma not otherwise specified, or synchronous multiple primary lung cancers. The median age was 64 years, and the female:male and never smoker:ever smoker ratios were 930:855 (52:48%) and 1167:604 (65:35%), respectively. The EGFR mutation rate was 56%. Among patients, 1093 (62%) had primary tumors in the upper lobes. Compared with the characteristics of the EGFR wild-type, tumors with EGFR activating mutations were more common in women (P < 0.001), never smokers (P < 0.001), and in the upper lobes (P = 0.004). Among EGFR activating mutations, compared with the EGFR exon 19 deletion, L858R mutation were more common in women (P = 0.002), never smokers (P = 0.038), and the upper lobes P < 0.0005). The present study is the first to address that different pulmonary lobar locations might harbor different EGFR mutation subtypes. We demonstrated that adenocarcinomas with L858R mutation, rather than exon 19 deletion or wild-type EGFR gene, prefer to locate over the upper lungs. This phenomenon was more significant in females and never-smokers, implying the result of complex interactions between genetic susceptibility and environmental factors. Therefore, EGFR L858R mutation and exon 19 deletion may not be identical disease entity from the point of carcinogenesis.

Poor prognosis of NSCLC located in lower lobe is partly mediated by lower frequency of EGFR mutations

“…Fourth, EGFR mutations could be the link between tumor location and prognosis. EGFR mutations are less likely to be detected in the lower lobe cancers 9 . Considering that EGFR mutation is a favorable predictive marker 23 , lower lobe cancers are expected to have poor prognosis than non-lower lobe cancers.…”

Location of stage I–III non‐small cell lung cancer and survival rate: Systematic review and meta‐analysis

“…attributed the better prognosis associated with upper lobe tumors to the easier approach, as fewer obstacles are encountered during treatment of upper lobe compared to lower lobe tumors . In addition, recently developed tyrosine kinase inhibitor agents are mainly used to treat adenocarcinoma or EGFR ‐positive NSCLC, both of which are more likely to manifest in the upper lobes …”

“…12 In addition, recently developed tyrosine kinase inhibitor agents are mainly used to treat adenocarcinoma or EGFR-positive NSCLC, both of which are more likely to manifest in the upper lobes. 10,11,29 Other researchers have reported different patterns of metastatic spread according to tumor location that eventually affect patient prognosis. Micrometastasis and subsequent relapse rates may be higher in lung bases with overperfusion.…”

“…Pathologic features have been elucidated according to the location of lung cancer. Higher proportions of adenocarcinoma, especially invasive adenocarcinoma, and EGFR positivity have been reported in patients with lung cancer in the upper lobe than in other regions …”

“…Higher proportions of adenocarcinoma, especially invasive adenocarcinoma, and EGFR positivity have been reported in patients with lung cancer in the upper lobe than in other regions. 10,11 The different clinicopathological features among various locations of NSCLC have focused attention on the relationship between the tumor site and prognosis. 8,[12][13][14][15][16][17][18][19][20] However, the conclusions of previous studies have been controversial because of the use of different settings for analysis, such as histology type, targeted tumor node metastasis (TNM) stage, treatment modality, differently divided lobes, and outcomes.…”