Premium
Adenocarcinoma of the pancreas
Author(s) -
Demeure Michael J.,
Doffek Kara M.,
Komorowski Richard A.,
Wilson Stuart D.
Publication year - 1998
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19981001)83:7<1328::aid-cncr9>3.0.co;2-e
Subject(s) - lymph , adenocarcinoma , pathology , medicine , histopathology , pancreas , micrometastasis , metastasis , lymph node , point mutation , stage (stratigraphy) , pancreatic disease , polymerase chain reaction , cancer , mutation , biology , gene , genetics , paleontology
BACKGROUND Stage I (T1‐2N0M0) adenocarcinoma of the pancreas is associated with a 5‐year survival rate of 15‐25%. Despite apparently curative resection and pathologic staging indicating localized disease, these cancers recur. The authors hypothesized that there exists microscopic regional disease that is not detected by surgical exploration or routine histopathology. METHODS Because 90‐95% of pancreatic cancers exhibit codon 12 K‐ ras mutations, the authors examined regional lymph nodes for mutated K‐ ras as a marker of metastasis. DNA was extracted from paraffin embedded archival specimens (primary tumors and histologically negative lymph nodes) of patients with Stage I pancreatic adenocarcinoma. The target region of K‐ ras was amplified by polymerase chain reaction (PCR) and tested for codon 12 mutation by BstN1 restriction digestion (restriction fragment length polymorphism [RFLP]) that recognized normal but not mutated sequences. Cell lines that harbored normal or mutated K‐ ras and resected jejunum or gallbladder were used as controls. The regional lymph nodes of 22 patients whose tumors harbored mutated K‐ ras were tested. RESULTS Dilution experiments with normal and mutant control cell line DNA demonstrated an assay sensitivity for mutated K‐ ras of 0.1%. Mutated K‐ ras was found in at least 1 regional lymph node in 16 (73%) of 22 patients with pathologic Stage I pancreatic adenocarcinoma, which suggested metastases not detected by routine histopathology. DNA sequence analysis was performed in four patients and confirmed identical point mutations in the primary tumor and accompanying PCR/RFLP positive lymph nodes. CONCLUSIONS Pathologic examination of regional lymph nodes in pancreatic adenocarcinoma specimens fails to detect metastases in many patients. Lymph node micrometastasis is one reason for the poor survival rates observed among patients with Stage I cancers. PCR/RFLP may have a role in staging early pancreatic cancers. Cancer 1998;83:1328‐1334. © 1998 American Cancer Society.