We examined the mutation statuses of the KRAS 12/13/61/146, NRAS 12/13/61/146, and BRAF 600 codons in genomic DNA from fresh-frozen or formalin-fixed paraffin-embedded tissues derived from 34 primary lesions and 52 corresponding PMs from 36 patients with CRC.
In group A, BRAF immunohistochemistry did not significantly differ between primary tumors and pulmonary metastases; no difference of BRAF expression was found between group A and B.
We retrospectively investigated the prognostic role of KRAS, BRAF, and PIK3CA (exon 20) mutations and loss of phosphatase and tensin homolog (PTEN) in surgically resected lung metastases.
Here we took advantage of the French National Cancer Institute Program of systematic molecular profiling of metastatic lung cancer, to collect clinical characteristics and analyze the outcome of consecutive patients with NSCLC harboring BRAF mutations at the Lyon University Hospital laboratory between February 2012 and October 2014.
Similarly, in the 1428 samples analyzed, BRAF mutations were less often found in liver metastases (N = 9/396; 2.3%) as compared to primary tumors (N = 79/959; 8.2%), lung metastases (N = 2/29; 6.9%), or other metastatic locations (N = 2/44; 4.5%; P < 0.0002).
These findings suggest that the BRAF(V600E) mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis.
In melanoma, V600K mutations in comparison to other BRAF mutations were associated with more frequent brain (75% vs. 36.3%, p = 0.02) and lung metastases (91.6% vs. 47.7%, p = 0.007), and shorter time from diagnosis to metastasis and to death (19 vs. 53 months, p = 0.046 and 78 vs. 322 months, p = 0.024 respectively).
A distinct pattern of metastatic spread was observed in BRAF mutant tumors, namely higher rates of peritoneal metastases (46% vs 24%, P = .001), distant lymph node metastases (53% vs 38%, P = .008), and lower rates of lung metastases (35% vs 49%, P = .049).
B-Raf(V600E) cells in which either B-Raf(V600E) or TSP-1 were knocked down were implanted orthotopically into the thyroids of immunocompromised mice, resulting in significant reduction in tumor size and fewer pulmonary metastases from the primary carcinoma as compared with the control cells.
Results indicated that knockdown of mutant (V600E)B-Raf inhibited melanoma cell extravasation in vitro and subsequent lung metastasis development in vivo.
Targeting B-Raf with the pharmacologic inhibitor BAY 43-9006, which was found ineffective in clinical trials and seems to act primarily as an angiogenesis inhibitor, did not decrease metastasis, whereas inhibition of Mek using U0126 decreased cellular proliferative capacity, thereby effectively reducing number and size of lung metastases.