Pujan Dave

Publications (2)13.19 Total impact

• Article: KRAS G>A mutation favors poor tumor differentiation but may not be associated with prognosis in patients with curatively resected duodenal adenocarcinoma.

  Tao Fu, Angela A Guzzetta, Jana Jeschke, Rajita Vatapalli, Pujan Dave, Craig M Hooker, Richard Morgan, Christine A Iacobuzio-Donahue, Baohua Liu, Nita Ahuja
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  ABSTRACT: KRAS mutations have been found in duodenal adenocarcinomas and may have prognostic significance. The purpose of this study was to classify clinicopathological characteristics, microsatellite instability, and KRAS mutations and identify possible prognostic role of KRAS mutations in duodenal adenocarcinomas. Demographics, tumor characteristics and survival were recorded for 78 patients with duodenal adenocarcinomas (stages I to III). KRAS mutations were detected in 27 (34.6%) cases, of which the majority (74.1%) were G>A transitions. Multivariate logistic regression analysis showed that KRAS G>A mutation was significantly associated with late stage (p = 0.025) and poor tumor differentiation (p = 0.035), when compared with wild-type and other than G>A mutations. KRAS G>A mutation carriers were at increased risk for distant relapse (p = 0.022) and had significantly shorter overall survival (OS; log-rank p = 0.045) and a trend toward shorter relapse-free survival (RFS; log-rank p = 0.062) when compared with those who did not carry the KRAS G>A mutation. In multivariate analyses, there was a significant correlation between ò 3 positive lymph nodes and poor OS (p < 0.001) and RFS (p = 0.001) and KRAS G>A mutation carriers demonstrated no effect on clinical outcome. In conclusion, KRAS G>A mutation correlates significantly with late stage and poor tumor differentiation in duodenal adenocarcinoma. Among patients who undergo a curative resection of duodenal adenocarcinoma, KRAS G>A mutation carriers will more likely experience distant relapse but may not exhibit a poor prognosis. Number of positive lymph nodes should be incorporated in future staging systems. © 2012 Wiley Periodicals, Inc.
  International Journal of Cancer 10/2012; · 5.44 Impact Factor
• Article: CpG island methylator phenotype-positive tumors in the absence of MLH1 methylation constitute a distinct subset of duodenal adenocarcinomas and are associated with poor prognosis.

  Tao Fu, Emmanouil P Pappou, Angela A Guzzetta, Jana Jeschke, Ruby Kwak, Pujan Dave, Craig M Hooker, Richard Morgan, Stephen B Baylin, Christine A Iacobuzio-Donahue, Christopher L Wolfgang, Nita Ahuja
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  ABSTRACT: Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis. Demographics, tumor characteristics, and survival were available for 99 duodenal adenocarcinoma patients. Testing for KRAS and BRAF mutations, MSI, MLH1 methylation, and CpG island methylator phenotype (CIMP) status was conducted. A Cox proportional hazard model was built to predict survival. CIMP(+) was detected in 27 of 99 (27.3%) duodenal adenocarcinomas and was associated with MSI (P = 0.011) and MLH1 methylation (P < 0.001), but not with KRAS mutations (P = 0.114), as compared with CIMP(-) tumors. No BRAF V600E mutation was detected. Among the CIMP(+) tumors, 15 (55.6%) were CIMP(+)/MLH1-unmethylated (MLH1-U). Kaplan-Meier analysis showed that tumors classified by CIMP, CIMP/MLH1 methylation status, or CIMP/MSI status could predict overall survival (OS; P = 0.047, 0.002, and 0.002, respectively), whereas CIMP/MLH1 methylation status could also predict time-to-recurrence (TTR; P = 0.016). In multivariate analysis, CIMP/MLH1 methylation status showed a significant prognostic value in both OS (P < 0.001) and TTR (P = 0.023). Patients with CIMP(+)/MLH1-U tumors had the worst OS and TTR. Our results showed existence of CIMP in duodenal adenocarcinomas. The combination of CIMP(+)/MLH1-U seems to be independently associated with poor prognosis in patients with duodenal adenocarcinomas. This study also suggests that BRAF mutations are not involved in duodenal tumorigenesis, MSI, or CIMP development.
  Clinical Cancer Research 07/2012; 18(17):4743-52. · 7.74 Impact Factor