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BRAF-mutated, Microsatellite-stable Adenocarcinoma of the Proximal Colon

Overview of attention for article published in The American Journal of Surgical Pathology, May 2012
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Title
BRAF-mutated, Microsatellite-stable Adenocarcinoma of the Proximal Colon
Published in
The American Journal of Surgical Pathology, May 2012
DOI 10.1097/pas.0b013e31824430d7
Pubmed ID
Authors

Reetesh K. Pai, Priya Jayachandran, Albert C. Koong, Daniel T. Chang, Shirley Kwok, Lisa Ma, Daniel A. Arber, Raymond R. Balise, Raymond R. Tubbs, Bonnie Shadrach, Rish K. Pai

Abstract

The association of BRAF V600E mutation and the presence of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) often confound analysis of BRAF mutation status and survival in colorectal carcinoma. We evaluated a consecutive series of proximal colonic adenocarcinomas for mismatch repair protein abnormalities/MSI, BRAF V600E mutation, and KRAS mutations in an attempt to determine the prognostic significance of these abnormalities and to correlate histopathologic features with molecular alterations. Of the 259 proximal colon adenocarcinomas analyzed for mismatch repair protein abnormalities and/or MSI, 181 proximal colonic adenocarcinomas demonstrated proficient DNA mismatch repair using either MSI PCR (n=78), mismatch repair protein immunohistochemistry (n=91), or both MSI PCR and mismatch repair immunohistochemistry (n=12); these were tested for the BRAF V600E mutation and KRAS mutations. Compared with BRAF wild-type adenocarcinomas, BRAF-mutated adenocarcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (16/20, 80% vs. 75/161, 47%; P=0.008), mean number of lymph node metastases (4.5 vs. 2.2; P=0.01), perineural invasion (8/20, 40% vs. 13/161, 8%; P=0.0004), and high tumor budding (16/20, 80% vs. 83/161, 52%; P=0.02). BRAF-mutated adenocarcinomas frequently contained areas with mucinous histology (P=0.0002) and signet ring histology (P=0.03), compared with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas. Clinical follow-up data were available for 173 proximal colonic adenocarcinomas with proficient DNA mismatch repair. Patients with BRAF-mutated adenocarcinomas had a median survival of 12.3 months with a 1-year probability of survival of 54% and a 1-year disease-free survival of 56%. Patients with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas had significantly improved overall survival (unadjusted log-rank P=0.03 and unadjusted log-rank P=0.0002, respectively) and disease-free survival (unadjusted log-rank P=0.02 and unadjusted log-rank P=0.02, respectively) compared with patients with BRAF-mutated adenocarcinomas. When adjusting for tumor stage, survival analysis demonstrated that patients with BRAF-mutated adenocarcinoma had a significantly poor overall survival and disease-free survival (hazard ratios 6.63, 95% CI, 2.60-16.94; and 6.08, 95% CI, 2.11-17.56, respectively) compared with patients with KRAS/BRAF wild-type adenocarcinomas. No significant difference in overall or disease-free survival was identified between patients with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas. Our results demonstrate that BRAF-mutated proximal colon adenocarcinomas with proficient DNA mismatch repair have a dismal prognosis with an aggressive clinical course and often display mucinous differentiation, focal signet ring histology, and other adverse histologic features such as lymphatic and perineural invasion and high tumor budding.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 62 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 19%
Other 7 11%
Student > Postgraduate 6 10%
Professor 4 6%
Student > Ph. D. Student 4 6%
Other 13 21%
Unknown 16 26%
Readers by discipline Count As %
Medicine and Dentistry 34 55%
Biochemistry, Genetics and Molecular Biology 4 6%
Agricultural and Biological Sciences 3 5%
Nursing and Health Professions 1 2%
Social Sciences 1 2%
Other 1 2%
Unknown 18 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 April 2012.
All research outputs
#17,286,379
of 25,374,647 outputs
Outputs from The American Journal of Surgical Pathology
#2,819
of 3,522 outputs
Outputs of similar age
#115,295
of 175,822 outputs
Outputs of similar age from The American Journal of Surgical Pathology
#26
of 35 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,522 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one is in the 9th percentile – i.e., 9% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 175,822 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.