Non-small Cell Lung Cancer with Concomitant <i>EGFR</i>, <i>KRAS</i>, and <i>ALK</i> Mutation: Clinicopathologic Features of 12 Cases

Abstract

Background:Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy. Methods:In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features. Results:All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had KRAS mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation. Conclusions:EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

Open-Sourced CIViC Annotation Pipeline to Identify and Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes

“…Associated evidence items provide a brief description of the clinical relevance, links to CIViC evidence items, and associated citations. An illustrative output report that displays most OpenCAP features, including CIViC variant descriptions and CIViC assertions, was created using a previously reported patient from the literature 27 (Data Supplement).…”

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

“…The coexistence of mutations in a patient may be a consequence of intratumoral heterogeneity due to coexisting divergent clones within the same tumor. 49,50 Tumors with EGFR and KRAS co-positivity generally show histologic features typical of EGFR positive cases (predominant acinar pattern). 49 Similarly, 3 of our 4 cases with dual positivity had acinar histology.…”

“…49,50 Tumors with EGFR and KRAS co-positivity generally show histologic features typical of EGFR positive cases (predominant acinar pattern). 49 Similarly, 3 of our 4 cases with dual positivity had acinar histology. Further, it has been hypothesized that presence of coexisting mutations is associated with an aggressive disease profile with suboptimal response to therapy.…”

Influence of EGFR-activating mutations on sensitivity to tyrosine kinase inhibitors in a KRAS mutant non-small cell lung cancer cell line

“…In NSCLC prior to treatment, the majority of oncogenic driver mutations are mutually exclusive with other mutations [5,6]. However, recent studies have shown that additional driver mutations such as KRAS, ALK, and PI3K mutations co-exist with EGFR-mutations in a certain percentage of lung cancers [5,[7][8][9][10][11][12][13][14]. Of note, these driver mutations have been found not only in different cell populations in tumors, but also within the same cell population [15,16].…”