Molecular Detection of Neoplastic Cells in Lymph Nodes of Metastatic Colorectal Cancer Patients Predicts Recurrence

• Published in: Clinical cancer research Vol. 5; no. 9; pp. 2450 - 2454
• Main Authors: SANCHEZ-CESPEDES, M, ESTELLER, M, HIBI, K, COPE, F. O, WESTRA, W. H, PIANTADOSI, S, HERMAN, J. G, JIN JEN, SIDRANSKY, D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-09-1999
• Subjects: Biological and medical sciences; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Genes, ras; Genetic Markers; Humans; Liver Neoplasms - diagnosis; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Lymph Nodes - pathology; Lymphatic Metastasis; Medical sciences; Mutation; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Predictive Value of Tests; Prognosis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Analysis; Tumors; Human; Relapse; Rectal disease; Lymph node; Prediction; Biological marker; Hepatic disease; Metastasis; Malignant tumor; CDKN2 gene; Colonic disease; Polymerase chain reaction; TP53 Gene; Rectum; Digestive diseases; Intestinal disease; Advanced stage; Colon; Mutation; Onc gene; Methylation; Tumor cell
• ISSN: 1078-0432; 1557-3265

Disseminated disease, especially to the liver, constitutes the major risk of recurrence for colorectal cancer patients. However,
successful resection can still be achieved in 25–35% of colorectal cancer patients with isolated metastases. To evaluate the
clinical value of occult micrometastatic disease detection in lymph nodes, we tested genetic (K- ras and p53 gene mutations) and epigenetic ( p16 promoter hypermethylation) molecular markers in the perihepatic lymph nodes from colorectal cancer patients with isolated
liver metastases. DNA was extracted from 21 paraffin-embedded liver metastases and 80 lymph nodes from 21 colorectal cancer
patients. K- ras and p53 gene mutations were identified in DNA from liver metastases by PCR amplification followed by cycle sequencing. A sensitive
oligonucleotide-mediated mismatch ligation assay was used to search for the presence of K- ras and p53 mutations to detect occult disease in 68 lymph nodes from tumors positive for these gene mutations. Promoter hypermethylation
at the p16 tumor suppressor gene was examined in both liver lesions and lymph nodes by methylation-specific PCR. Sixteen of the 21 (76%)
liver metastases harbored either gene point mutations or p16 promoter hypermethylation. Twelve of the 68 lymph nodes were positive for tumor cells by molecular evaluation and negative
for tumor cells by histopathology and cytokeratin immunohistochemistry, whereas none were positive for tumor cells by histopathology
or negative for tumor cells by molecular analysis ( P = 0.0005, McNemar’s test). Moreover, in three patients with lymph nodes that were histologically negative at all sites, molecular
screening detected tumor DNA at one or more lymph nodes. Survival analysis showed a median survival of 1056 days for patients
without evidence of lymph node involvement by molecular analysis and 165 days for patients with positive lymph nodes by this
approach ( P = 0.0005). These results indicate that lymph node metastasis screening in colorectal cancer patients by molecular-based techniques
increases the sensitivity of tumor cell detection and can be a good predictor of recurrence in colorectal cancer patients
with resectable liver metastases.