Phenotypic Correlates of ERBB2, BRAF and PIK3CA Mutations in Non-Small Cell Lung Cancer.
Wanghai Zhang, Victoria Joshi, Stephanie Heon, Leena Gandhi, David Jackman, Neal Lindeman, Lynette Sholl. Brigham and Women's Hospital, Boston; Partners Center for Genomic Medicine, Boston; Massachussetts General Hospital, Boston; Dana-Farber Cancer Institute, Boston
Background: A subset of non small cell lung carcinomas (NSCLC) contains mutations in EGFR/ERBB1 or in downstream oncogenes. EGFR and KRAS mutations are the most common, occurring in ∼30% of NSCLC, but similar, less frequent, mutations occur in ERBB2, BRAF and PIK3CA. While EGFR-and KRAS- mutant NSCLC are more frequently associated with bronchioloalveolar (BAC)/papillary and solid histologies, respectively, the histologic features associated with NSCLC bearing ERBB2, BRAF or PIK3CA mutations have not been fully described.
Design: 407 cases of NSCLC were tested for EGFR, KRAS, ERBB2, BRAF and PIK3CA mutation by PCR-Sanger sequencing from 8/2009 – 8/2010. H&E slides from NSCLC with a mutation in ERBB2, BRAF, or PIK3CA were reviewed, to examine correlations between genotype and morphology.
Results: 35/407 cases (8.6%) contained one of the selected non-EGFR/KRAS mutations, 14 (3.4%) ERBB2, 15 (3.7%) BRAF, and 6 (1.5%) PIK3CA mutations. H&E slides were available for 25 cases (10 ERBB2, 9 BRAF, 6 PIK3CA mutants). Non-EGFR/KRAS mutations were mutually exclusive though one tumor contained PIK3CA and EGFR mutations. Table 1 shows the histologic features of each genotype: ERBB2-mutant tumors tended towards acinar/papillary histology, and BRAF-mutant tumors tended towards high grade/solid histology, often (4/9) with signet ring cells, while PIK3CA mutations occurred in tumors with adenosquamous, mixed subtype adenocarcinoma, mucinous BAC and sarcomatoid histologies. Other morphologic features, including inflammation and desmoplasia, did not predict genotype.
|Squamous cell carcinoma||0||0||0|
|Clear cell change||2||2||1|
|Signet ring cells||0||4||1|