Kras mutations and p53 overexpression in pseudomyxoma peritonei

Association with phenotype and prognosis

Shreya Shetty, Peter Thomas, Bala Ramanan, Poonam K Sharma, Venkatesh Govindarajan, Brian W. Loggie

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)97-103
Number of pages7
JournalJournal of Surgical Research
Volume180
Issue number1
DOIs
StatePublished - Mar 2013

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Pseudomyxoma Peritonei
Phenotype
Mutation
Codon
Survival
Colorectal Neoplasms
Carcinoma
Kaplan-Meier Estimate
Mucins
Chi-Square Distribution
Survival Analysis
Adenoma
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Kras mutations and p53 overexpression in pseudomyxoma peritonei : Association with phenotype and prognosis. / Shetty, Shreya; Thomas, Peter; Ramanan, Bala; Sharma, Poonam K; Govindarajan, Venkatesh; Loggie, Brian W.

In: Journal of Surgical Research, Vol. 180, No. 1, 03.2013, p. 97-103.

Research output: Contribution to journalArticle

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title = "Kras mutations and p53 overexpression in pseudomyxoma peritonei: Association with phenotype and prognosis",
abstract = "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.",
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AU - Govindarajan, Venkatesh

AU - Loggie, Brian W.

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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.

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