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Adenocarcinoma of the pancreas: detection of occult metastases in regional lymph nodes by a polymerase chain reaction-based assay.
Cancer. 1998 Oct 01; 83(7):1328-34.C

Abstract

BACKGROUND

Stage I (T1-2NOM0) 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.

Authors+Show Affiliations

Department of Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9762933

Citation

Demeure, M J., et al. "Adenocarcinoma of the Pancreas: Detection of Occult Metastases in Regional Lymph Nodes By a Polymerase Chain Reaction-based Assay." Cancer, vol. 83, no. 7, 1998, pp. 1328-34.
Demeure MJ, Doffek KM, Komorowski RA, et al. Adenocarcinoma of the pancreas: detection of occult metastases in regional lymph nodes by a polymerase chain reaction-based assay. Cancer. 1998;83(7):1328-34.
Demeure, M. J., Doffek, K. M., Komorowski, R. A., & Wilson, S. D. (1998). Adenocarcinoma of the pancreas: detection of occult metastases in regional lymph nodes by a polymerase chain reaction-based assay. Cancer, 83(7), 1328-34.
Demeure MJ, et al. Adenocarcinoma of the Pancreas: Detection of Occult Metastases in Regional Lymph Nodes By a Polymerase Chain Reaction-based Assay. Cancer. 1998 Oct 1;83(7):1328-34. PubMed PMID: 9762933.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenocarcinoma of the pancreas: detection of occult metastases in regional lymph nodes by a polymerase chain reaction-based assay. AU - Demeure,M J, AU - Doffek,K M, AU - Komorowski,R A, AU - Wilson,S D, PY - 1998/10/8/pubmed PY - 2000/6/20/medline PY - 1998/10/8/entrez SP - 1328 EP - 34 JF - Cancer JO - Cancer VL - 83 IS - 7 N2 - BACKGROUND: Stage I (T1-2NOM0) 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. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/9762933/Adenocarcinoma_of_the_pancreas:_detection_of_occult_metastases_in_regional_lymph_nodes_by_a_polymerase_chain_reaction_based_assay_ L2 - https://medlineplus.gov/pancreaticcancer.html DB - PRIME DP - Unbound Medicine ER -