Journal
ANNALS OF ONCOLOGY
Volume 25, Issue 11, Pages 2230-2236Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdu367
Keywords
KRAS-variant; cisplatin; cetuximab; p16 expression; head and neck squamous cell carcinoma
Categories
Funding
- NIH NIDCR [R01 (DE017982)]
- NIH [R01 CA157749-01A1]
- Public Health Service from the National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA16116, CA27525, CA13650, CA9957]
- Department of Health and Human Services
Ask authors/readers for more resources
A germline mutation in the 3'-untranslated region of KRAS (rs61764370, KRAS-variant: TG/GG) which disrupts microRNA regulation has previously been associated with altered patient outcome and drug sensitivity in various cancers. Our study suggests this KRAS-variant is a potential predictive biomarker for poor platinum response in recurrent/metastatic head and neck squamous cell carcinoma patients.A germline mutation in the 3'-untranslated region of KRAS (rs61764370, KRAS-variant: TG/GG) has previously been associated with altered patient outcome and drug resistance/sensitivity in various cancers. We examined the prognostic and predictive significance of this variant in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We conducted a retrospective study of 103 HNSCCs collected from three completed clinical trials. KRAS-variant genotyping was conducted for these samples and 8 HNSCC cell lines. p16 expression was determined in a subset of 26 oropharynx tumors by immunohistochemistry. Microarray analysis was also utilized to elucidate differentially expressed genes between KRAS-variant and non-variant tumors. Drug sensitivity in cell lines was evaluated to confirm clinical findings. KRAS-variant status was determined in 95/103 (92%) of the HNSCC tumor samples and the allelic frequency of TG/GG was 32% (30/95). Three of the HNSCC cell lines (3/8) studied had the KRAS-variant. No association between KRAS-variant status and p16 expression was observed in the oropharynx subset (Fisher's exact test, P = 1.0). With respect to patient outcome, patients with the KRAS-variant had poor progression-free survival when treated with cisplatin (log-rank P = 0.002). Conversely, KRAS-variant patients appeared to experience some improvement in disease control when cetuximab was added to their platinum-based regimen (log-rank P = 0.04). The TG/GG rs61764370 KRAS-variant is a potential predictive biomarker for poor platinum response in R/M HNSCC patients. NCT00503997, NCT00425750, NCT00003809.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available