Although BRAF mutations are found in 1.8% of advanced adenocarcinoma patients without EGFR/ALK aberration, they may be able to serve as a treatment target in those patients.
None of the MMRD small bowel adenocarcinomas harbored the BRAFV600E mutation, whereas 60% of MMRD colorectal carcinomas were positive for BRAF V600E with concurrent loss of MLH1 and PMS2 expression.
The identification of BRAF mutations and the frequently present KRAS wild-type status principally render some mixed adenoneuroendocrine carcinomas eligible to targeted treatment strategies used for colorectal adenocarcinomas.
Changes in the epidermal growth factor receptor (<i>EGFR</i>) gene, Kirsten rat sarcoma viral oncogene (<i>KRAS</i>), v-Raf murine sarcoma viral oncogene homolog B (<i>BRAF</i>), gene encoding neurofibromin (<i>NF1</i>), anaplastic lymphoma kinase (<i>ALK</i>) and <i>ROS1</i> are the main genes that suffer alterations in the tumors of patients with ADC.
There was a significant association between BRAF mutations and adenocarcinomas (ADCs) in NSCLC compared with non-ADCs (OR = 3.96, 95% CI = 2.13-7.34, P < 0.0001).
IHC cytoplasmic expression of BRAFV600E (VE1) protein was found in two of 95 cases: one case of adenocarcinoma NOS (one of three; 33%) and one case of carcinoma ex pleomorphic adenoma (one of five; 20%).
Compared to patients with non-BRAF mutation, patients with BRAF mutations were associated with adenocarcinomas (89.3% vs. 70.6%, P = 0.048) and never smokers (78.6% vs. 56.7%, P = 0.019).
No correlation was detected between mesothelin expression and mismatch repair system deficient phenotype or gene mutation (BRAF and RAS) status in gastrointestinal adenocarcinomas.
Comparison of the study group of 60 mucinous adenocarcinomas defined according to World Health Organization classification with control group of 136 colorectal adenocarcinomas successively removed shows higher frequency of BRAF and KRAS mutations and microsatellite instability-high status and lower frequency of wnt signaling pathway activation in mucinous adenocarcinomas.
The median age was 60.1 ± 14.5 (standard deviation) years; 89% (n = 106/119) had performance status 0/1 at diagnosis; 79% (n = 103/130) were non- or former smokers; 93% (n = 120/129) had adenocarcinomas and 74%(n = 97)/19%(n = 25)/7%(n = 10) had disease stages IV/III/I-II at diagnosis, respectively; co-mutations included EGFR (n = 2), BRAF (n = 2), KRAS (n = 1), and HER2 (n = 1).
The histologic features of BRAF-mutated adenocarcinomas have not yet been established, but papillary, lepidic, solid, and acinar patterns have been observed.
But the status of KRAS and BRAF mutations and their clinicopathologic and prognostic significance has not been extensively evaluated in small intestinal adenocarcinomas.
We analyzed 32 colorectal poorly differentiated neuroendocrine carcinomas and 40 colorectal poorly differentiated conventional adenocarcinomas for mutations in KRAS and BRAF and for DNA mismatch repair protein abnormalities to correlate histopathology with molecular alterations and survival.
Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease).
In addition, MC had a higher MMRd rate (0.892, 95% CI 0.758-0.956), higher BRAF(V600E) mutation rate (0.652, 95% CI 0.143-0.954) and lower KRAS mutation rate (0.171, 95% CI 0.065-0.378) than PDA/UDA and conventional adenocarcinoma.
Twenty-one BRAF mutations were identified in 951 patients with adenocarcinomas (2.2%; 95% confidence interval [CI], 1.4%-3.4%): 17 (81%; 95% CI, 60%-92%) were BRAF(V600E) mutations, and 4 were non-BRAF(V600E) mutations.
These polyps contain BRAF mutations and are prone to epigenetic methylation that ultimately silences MLH1, leading to MSI and heralding progression of dysplasia to invasive adenocarcinoma.
Formalin Fixed Paraffin Embedded tissue were studied for miRNA expression, KRAS, BRAF, PIK3CA mutations, and immuno-histochemistry for APC and p53 proteins for normal colon (n=11), hyperplastic polyps (n=11), high grade adenomas (n=10), low grade adenomas (n=34) and adenocarcinoma (n=13).