Detection of K-ras point mutation at codon 12 in pancreatic diseases: a study in a Brazilian casuistic.
OBJECTIVE
To clarify the sensitivity and the validity of K-ras point mutational analysis at codon 12 in Brazilian patients with pancreatic diseases, and the possible correlation between the presence of the mutation and the histopathological findings.


METHODS
Ninety-seven Brazilian patients with pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumors and chronic pancreatitis were enrolled in this study. Forty-five patients (46%) were female and 52 patients (54%) were male, having an average age of 60.2+/-9.2 years for adenocarcinoma (n=52), 45.1+/-19.4 years for pancreatic neuroendocrine tumors (n=20), and 46.4+/-11.2 years for chronic pancreatitis (n=25). DNA extracted from 11 normal human peripheric lymphocytes was utilized as a control.


RESULTS
The sensitivity of K-ras mutational analysis was 83.3% (25/30) in paraffin-embedded samples and 72.7% (16/22) in surgically resected specimens of the malignancy. On the other hand, no mutations were found in pancreatic neuroendocrine tumors or in chronic pancreatitis. Regarding the histopathological grading, the higher positivity rate was found in poorly-differentiated adenocarcinoma (100%), and progressively decreased in moderately-differentiated adenocarcinoma (72.2%), and well-differentiated adenocarcinoma (66.6%). The positivity rate in non-classified adenocarcinoma was 81.8%.


CONCLUSIONS
K-ras point mutation, in our study, is notably prevalent in malignancies and is absent in chronic pancreatitis and pancreatic neuroendocrine tumors. These results encourage us to consider the possibility of treatment strategies for this oncogene in the future.
Kubrusly
Márcia Saldanha
MS
Department of Gastroenterology, Faculty of Medicine, University of Sao Paulo. Sao Paulo, Brazil.
Cunha
José Eduardo Monteiro
JE
Bacchella
Telésforo
T
Abdo
Emilio Elias
EE
Jukemura
José
J
Penteado
Sonia
S
Morioka
Cíntia Yoko
CY
de Souza
Lourenilson José
LJ
Machado
Marcel Cerqueira Cesar
MC
D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D002908:Chronic Disease; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics; D010182:Pancreatic Diseases / Q000235:genetics*; D010183:Pancreatic Ducts / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics; D010195:Pancreatitis / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012680:Sensitivity and Specificity
D003062:Codon; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)