Clinicopathological features of lung adenocarcinoma with KRAS mutations

Abstract

BACKGROUND: KRAS and epidermal growth factor receptor (EGFR) mutations are thought to play an important role in the carcinogenesis of lung adenocarcinoma. However, clinicopathological findings of KRAS mutated adenocarcinoma cases have not yet been fully clarified. The authors analyzed the relationship between the KRAS mutation and corresponding clinicopathological findings, focusing on nonmucinous and mucinous bronchioloalveolar elements. METHODS: EGFR and KRAS mutations were detected in DNA samples extracted from 182 surgically resected tissues of lung adenocarcinomas by the Smart Amplification Process. The relations between gene mutation status and clinicopathological features were analyzed. All adenocarcinoma cases were divided into bronchioloalveolar carcinoma (BAC), adenocarcinoma with bronchioloalveolar features, and adenocarcinoma without BAC components (non‐BAC). BAC/adenocarcinoma with bronchioloalveolar features tumors were further assessed for the presence of mucinous features. RESULTS: EGFR and KRAS mutations were found in 76 and 30 cases, respectively. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features was found in 22 cases, which included 10 nonmucinous and 12 mucinous tumors. Of 19 cases with mucinous BAC/adenocarcinoma with bronchioloalveolar features, KRAS mutations were detected in 12, but no EGFR mutation was detected. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features had significantly earlier pathological stages and more favorable prognoses than did non‐BAC. Mucinous BAC/adenocarcinoma with bronchioloalveolar features showed less smoking history than did nonmucinous BAC/adenocarcinoma with bronchioloalveolar features and non‐BAC. Furthermore, transversion type KRAS mutations were more common in non‐BAC. CONCLUSIONS: KRAS mutated adenocarcinomas can be divided into BAC/adenocarcinoma with bronchioloalveolar features and non‐BAC types. Non‐BAC adenocarcinoma is related to smoking history and has a poor prognosis. BAC/adenocarcinoma with bronchioloalveolar features adenocarcinoma, however, has a more favorable prognosis, and mucinous BAC/adenocarcinoma with bronchioloalveolar features has little relationship to smoking history. Cancer 2011;. © 2011 American Cancer Society.

Molecular characterization of pulmonary sarcomatoid carcinoma: analysis of 33 cases

“…Furthermore, KRAS mutations were often observed in conjunction with TP53 mutations in sarcomatoid carcinoma, which are invariably high grade, as opposed to the low-grade mucinous morphology that is classically associated with KRAS mutations alone. 28 Some of our KRASmutated tumors showed areas of typical mucinous adenocarcinoma, with abrupt transition to high-grade sarcomatoid areas; these relatively 'dedifferentiated' areas may correspond to the accumulation of additional genetic hits associated with tumor progression, including mutations in TP53. However, as the mutations in these morphologically distinct areas of the tumor were not investigated separately, this cannot be confirmed from our data.…”

Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification

“…Wang et al (26) did not identify any significant differences in histological subtypes between the KRAS mutations and the wild-types; whereas, Yoshizawa et al (14) and Kakegawa et al (28) indicated that KRAS mutations were significantly associated with adenocarcinoma of mucinous tumor subtypes (P<0.001). Rekhtman et al (29) showed that KRAS mutations occurred more often in adenocarcinomas with a solid growth pattern (P=0.022).…”

Postrecurrence survival of surgically resected pulmonary adenocarcinoma patients according to EGFR and KRAS mutation status

“…Notably, no patients with KRAS-mutated tumors with distant recurrence survived for >2 years after the recurrence, except 1 patient with pure invasive mucinous adenocarcinoma. It was demonstrated that KRAS-mutated adenocarcinomas may be divided into two groups according to lepidic histological growth pattern, with those patients without a lepidic component exhibiting a poor prognosis (17). In this study, 6 adenocarcinoma patients with no lepidic component were included, all of whom succumbed to the disease within 2 years of recurrence, whereas patients with tumors with a lepidic component also exhibited poor postrecurrence prognosis.…”

“…Genomic DNA was extracted from a 3-5 mm cube of tumor tissue using a DNA Mini kit (Qiagen, Hilden, Germany) and subsequently diluted to a concentration of 20 ng/µl. KRAS and EGFR mutations in lung cancer tissue were analyzed by peptide nucleic acid-enriched sequencing, as previously described (15)(16)(17).…”