TY - JOUR
T1 - Kras mutations and p53 overexpression in pseudomyxoma peritonei
T2 - Association with phenotype and prognosis
AU - Shetty, Shreya
AU - Thomas, Peter
AU - Ramanan, Bala
AU - Sharma, Poonam
AU - Govindarajan, Venkatesh
AU - Loggie, Brian
N1 - Funding Information:
Supported by the Creighton University Patients Cancer Research Fund .
PY - 2013/3
Y1 - 2013/3
N2 - Background: Little information exists on Kras mutations and p53 overexpression in pseudomyxoma peritonei (PMP). These genetic alterations are associated with poorer prognoses in colorectal cancer. We postulated that these mutations might be more frequent in high-grade (HG) PMP (peritoneal mucinous carcinomatosis) versus low-grade (LG) PMP (disseminated peritoneal adenomucinosis/peritoneal mucinous carcinomatosis), for which survival differences are well documented. Methods: We collected data retrospectively on patients with PMP of appendiceal origin tested for Kras mutation (commercial assay) and p53 overexpression (immunohistochemistry). We used Fisher's exact test, chi-square test, and Kaplan-Meier survival curves for analysis. Results: Of 64 cases with Kras mutations, 25 were classified as LG and 39 as HG PMP. Median age at diagnosis was 53 ± 11.5 y. We detected Kras mutations in 37 of 64 patients (57.8%). In LG PMP, 15 of 25 (60%) were Kras mutant versus 22 of 39 (56.4%) in HG PMP (P = 0.80). Nearly 89% of mutations were seen in codon 12. We noted overexpression of p53 in 44.3% (86 of 194) of patients overall, which was significantly different between LG PMP and HG PMP: 35.5% (37 of 104) versus 54.4% (49 of 90), respectively (P = 0.009). Kras mutations did not affect prognosis. Overexpression of p53 was associated with a worse outcome. Conclusions: Kras mutation and p53 overexpression rates are comparable to those of colorectal adenomas and mucinous colorectal cancer. Codon 12 mutations may be associated with mucin production. Kras mutation status is not prognostic for overall survival. Overexpression of p53 was significantly correlated with female sex, higher-grade disease, and worse survival.
AB - Background: Little information exists on Kras mutations and p53 overexpression in pseudomyxoma peritonei (PMP). These genetic alterations are associated with poorer prognoses in colorectal cancer. We postulated that these mutations might be more frequent in high-grade (HG) PMP (peritoneal mucinous carcinomatosis) versus low-grade (LG) PMP (disseminated peritoneal adenomucinosis/peritoneal mucinous carcinomatosis), for which survival differences are well documented. Methods: We collected data retrospectively on patients with PMP of appendiceal origin tested for Kras mutation (commercial assay) and p53 overexpression (immunohistochemistry). We used Fisher's exact test, chi-square test, and Kaplan-Meier survival curves for analysis. Results: Of 64 cases with Kras mutations, 25 were classified as LG and 39 as HG PMP. Median age at diagnosis was 53 ± 11.5 y. We detected Kras mutations in 37 of 64 patients (57.8%). In LG PMP, 15 of 25 (60%) were Kras mutant versus 22 of 39 (56.4%) in HG PMP (P = 0.80). Nearly 89% of mutations were seen in codon 12. We noted overexpression of p53 in 44.3% (86 of 194) of patients overall, which was significantly different between LG PMP and HG PMP: 35.5% (37 of 104) versus 54.4% (49 of 90), respectively (P = 0.009). Kras mutations did not affect prognosis. Overexpression of p53 was associated with a worse outcome. Conclusions: Kras mutation and p53 overexpression rates are comparable to those of colorectal adenomas and mucinous colorectal cancer. Codon 12 mutations may be associated with mucin production. Kras mutation status is not prognostic for overall survival. Overexpression of p53 was significantly correlated with female sex, higher-grade disease, and worse survival.
KW - Appendix
KW - Kras
KW - Prognosis
KW - Pseudomyxoma peritonei
KW - p53
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U2 - 10.1016/j.jss.2012.10.053
DO - 10.1016/j.jss.2012.10.053
M3 - Article
C2 - 23199549
AN - SCOPUS:84873729543
SN - 0022-4804
VL - 180
SP - 97
EP - 103
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -