PREVALENCE AND CLINICAL-SIGNIFICANCE OF COMBINED K-RAS MUTATION AND P53 ABERRATION IN PANCREATIC ADENOCARCINOMA

Conclusion. This study could not attribute survival differences to the coincident acquisition of two common genetic alterations, K-ras mutat ion and p53 overexpression in pancreatic adenocarcinoma patients. Addi tionally, our data indicate the converse to be true: Those patients la cking both K-ras mutation and aberrant p53 expression showed the short est survival when compared with cases showing either alteration or bot h. This study also showed the negative effect of K-ras mutation and p5 3 expression on pancreas cancer patients' survival after treatment wit h either radiation therapy or chemotherapy. Background. Mutations of t he oncogene K-ras at codon 12 are reported to be the most common genet ic alteration in pancreatic carcinoma, whereas either overexpression o r mutation of the tumor suppressor p53 gene is considered the most com mon genetic alteration in neoplasia of all types. p53 overexpression h as been attributed to survival differences in pancreatic carcinoma, bu t such association is still controversial. No studies have fully docum ented the combined incidence of K-ras and p53 alterations in pancreati c adenocarcinoma, or their combined effect on patient survival in a la rge case series. The influence of radiation or chemotherapy in groups showing both, either, or neither mutation is also undocumented. Method s. Paraffin-embedded tissue sections from 76 cases of pancreatic adeno carcinoma were cut for DNA extraction for K-ras analysis and immunohis tochemical staining for aberrant p53 expression. K-ras mutation was de termined by single-strand conformation polymorphism (SSCP) and slot-bl ot allele-specific oligonucleotide (ASO) hybridization of PCR-amplifie d DNA product. p53 expression was scored on the basis of percent nucle ar staining with the MAb DO7. Results. Sixty-four of 76 cases (84%) sh owed K-ras mutation, p53 expression, or both. K-ras was mutated in 55 of 76 cases (72%), p53 was expressed in 33 of 76 cases (43%). Twenty-f our of 76 cases (31%) showed both K-ras mutation and p53 expression. T he presence of both alterations was not related to significant differe nces in tumor grade, stage, or survival compared to either alteration alone. A sizable subset (16% of cases) lacked either alteration, and s urprisingly, this group showed the shortest median survival compared t o those with K-ras mutation, p53 expression, or both (p = 0.024). Pati ents whose tumors were K-ras-negative showed the greatest difference i n median survival with radiation therapy (median survival 30.8 mo vs 7 .8 mo with no radiation, p = 0.005).