Primary lung adenocarcinoma is classified according to predominant histopathologic architecture into lepidic, papillary, acinar, solid, and micropapillary subtypes. These subtypes are related to overall survival in primary lung adenocarcinoma. The main goal of our work was to evaluate the prognostic impact of this classification on surgical resection of brain adenocarcinoma metastases in 97 patients with surgically resected brain metastases of lung adenocarcinoma from 2008 to 2017. Histopathologic subtype is associated with overall survival (P=0.0085): 30.1±5.6 months for papillary-predominant pattern, 26.5±6.3 months for acinar-predominant pattern, 13.8±1.4 months for solid pattern, 11.6±10.1 for micropapillary pattern. A “low grade” group comprising acinar and papillary-predominant pattern tumors showed a longer overall survival (28.5±4.1 mo) when compared with high-grade–predominant pattern (solid and micropapillary patterns) (13.7±1.4 mo), P=0.0011. On multivariate analysis, age below 55 years at the time of resection (hazard ratio, 3.56; 95% confidence interval, 1.12-11.31) and groups of architectural patterns (hazard ratio, 4.25; 95% confidence interval, 1.83-9.9) were related to overall survival (P=0.031 and 0.00078, respectively). Predominant architectural pattern evaluated on the surgical specimen of brain metastasis is a major prognostic factor of overall survival in metastatic lung adenocarcinoma.

Treatment for lung adenocarcinoma frequently diverges from standard treatment in older patients. Clinical, pathologic, and molecular characteristics of lung cancer in patients over 75 years old have not been fully described. The aim of our work was to describe the rate of EGFR, KRAS, BRAF, and HER2 mutations, and ALK rearrangement and pathologic characteristics in patients with lung adenocarcinoma over 75, compared with patients below 75 years old. This is a retrospective study from 2 cohorts: a histopathologic cohort of all consecutively resected lung adenocarcinoma in our institution for patients over 75 (n=54, from 2006 to 2017) compared with patients below 75 years old (n=148, from 2014 to 2017) and a molecular cohort of all stage IIIb or IV lung adenocarcinoma from 2009 to 2017 (n=1611). Papillary and lepidic components were more frequently found in patients over 75 years old (P=0.046 and 0.0078, respectively). The rate of current smokers was lower in older patients (P<0.0001). EGFR mutations were more frequent in patients over 75 than in younger patients: 17% versus 8.1% (P<0.0001). The mutually exclusive KRAS mutation was more frequent in patients below 75 years old than in older patients: 25.8% versus 12.8% (P<0.0001). There was no difference for the proportion of the 2 most frequent EGFR mutations (exon 19 deletion and L858R mutation) (P=0.85) or KRAS-mutated codon (P=0.22) between tumors in younger or older patients. There was no statistically significant difference for the presence of BRAF, HER2 mutations, and ALK rearrangement (P=0.44, 0.71, and 1, respectively). Our work highlights the fact that EGFR mutations are more frequent in patients over 75 years old in our population. We can hypothesize that this difference might be mainly caused by the less frequent occurrence of tobacco-smoking-related lung cancers in the elderly and the presence of a lepidic or papillary component in this age group.

Anti-CK7 and anti-CK20 immunohistochemistry is sometimes used to establish a diagnosis of primary lung cancer. We performed a retrospective study on the value of anti-CK7 and anti-CK20 immunohistochemistry in 359 biopsies of patients with suspected lung carcinoma in order to assess the usefulness of these antibodies in the evaluation of lung tumors in biopsies. Our results showed TTF-1 positivity in 73.3% of patients. EGFR mutations and ALK rearrangements were significantly different between TTF-1 positive and TTF-1 negative tumors (p < 0.001 and p = 0.023, respectively). Our results show a significant difference (p < 0.001) between TTF-1 positive and TTF-1 negative carcinomas with a median survival of 21.97 months (CI95% = 17.48–30.9 months) and 6.52 months (CI95% = 3.34–10.3 months), respectively. In the group of TTF-1 negative patients, anti-CK7 and CK20 immunohistochemistry was performed in 70 patients and showed CK7+/CK20- staining in 61 patients (87.1%), CK7-/CK20- in 4 patients (5.7%), CK7+/CK20+ in 3 patients (4.3%), and CK7-/CK20- in 2 patients (2.8%). No specific or molecular pattern was found in these groups of CK7/CK20 combinations. In total, this work brings arguments concerning the uselessness of anti-CK7/CK20 immunohistochemistry in the case of suspicion of primary lung cancer in biopsies.

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