[2051] Peripheral Lung Adenocarcinomas with Pleural Invasion Are More Likely To Harbor KRAS Mutation

Celina Villa, Anjana Yeldandi, Ritu Nayar, Philip Cagle, Kirtee Raparia. Northwestern University, Chicago, IL; The Methodist Hospital, Houston, TX

Background: Kirsten-RAS (KRAS) mutations are thought to play an important role in the pathogenesis of lung adenocarcinoma but the clinicopathologic features associated with this mutation have not been well described. We performed this study to determine the relationship between the KRAS mutation and demographics, tumor size, tumor grade, predominant architectural pattern, nodal status, pleural invasion and stage of cancer.
Design: KRAS mutations (all known mutations in codon 12 and codon 13 in exon 2 of the KRAS gene) were screened in 251 patients diagnosed with lung adenocarcinoma between 2008 and 2011. Mutational analysis was performed on DNA samples extracted from surgically resected/biopsied/cytologic specimens of lung adenocarcinomas by PCR and TrimGens's Shifted termination Assay. Relationships between gene mutation status and clinicopathological features were analyzed using appropriate parametric and non-parametric tests for significance.
Results: Of 251 tumors the frequency of KRAS mutations and no mutations (wild type) was 31% and 69% respectively. Mean age in the KRAS mutant group was 68 years (range 48 to 86 years) and male to female ratio 1:2.2. Seventy-three patient's samples were positive for KRAS codon 12 mutation (30 G12C, 15 G12A, 12 G12V, 9 G12D, 5 G12S and 2 G12T) and only 4 patient samples harbored codon 13 mutations (3 G13C and 1G13A). The tumor size in the mutant group was 2.8cm, compared to 2.4cm in non-mutant group. KRAS mutant patients had grade 2 adenocarcinoma in 61% and grade 1 and 3 in 12 and 27% patients respectively. Minimally invasive adenocarcinoma was seen in 7% of the patients with the mutant gene. The predominant pattern seen in the mutant group was acinar pattern (65% cases). Pleural invasion was seen in 20% of patients with KRAS mutant gene, compared to 6% in non-mutant patients(p=0.014). Nodal status was N0 in 56%, N1 in 8%, N2 in 8% and N3 in 2% cases of the mutant group. 41% of patients had Stage 1A and 1B disease, compared to Stage 2, 3 and 4 which was seen in 26%, 16% and 17% patients respectively in the mutant group.
Conclusions: KRAS mutation is more common in codon 12 in exon 2 of the KRAS gene in lung adenocarcinoma. Patients with KRAS mutation were similar to patients with wild type KRAS with respect to age, sex, predominant architectural pattern of adenocarcinoma, minimally invasive adenocarcinoma, tumor size, nodal status, tumor grade and stage of lung cancer. However patients with KRAS mutation were more likely to have pleural invasion when compared to patients with wild type KRAS gene.
Category: Pulmonary

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 298, Tuesday Morning

 

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