Lymphatic metastasis and nm23H1 genetic instability in Chinese colon cancer patients.
OBJECTIVE
To investigate the pathogenic mechanism of colon cancer at the molecular level and to elucidate the relationship between intercellular adhesion molecule-1 (ICAM-1) and nm23H(1) genes and Chinese patients with colon cancer.


METHODS
DNA was extracted from paraffin-embedded materials. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze MSI and LOH. Expression of ICAM-1 was detected by Envision immuno-histochemistry. Experimental results were analyzed with Leica-Qwin computer imaging techniques and SPSS software of statistics.


RESULTS
ICAM-1 expression of lymphatic endothelium was negative in normal colon and positive in colon cancer respectively. The number of lymphatics positive for ICAM-1 was gradually increased with degree of cancer invasion (P<0.01). In the group with metastasis of colon cancer, the number of lymphatics positive for ICAM-1 in lymph nodes was more than that in the group with no metastasis (P<0.01). The frequency of MSI, LOH and nm23H(1) protein was 26.67%, 20.00% and 53.33% in colon cancer, respectively. In TNM staging, MSI (43.75%) and nm23H(1) protein (81.25%) in stages I+II were detected more easily than the corresponding indexes (MSI: 7.14%, P<0.05 and nm23H(1): 21.43%, P<0.01) in stages III+IV. By comparison, the frequency of LOH (35.71%) in stages III+IV was more than that of LOH (6.25%, P<0.05) in stages I+II. LOH exhibited a rising trend along with the Duke's staging. nm23H(1) protein in the group of tubular adenocarcinoma (60.00%) was higher expressed than that in the group of mucoid adenocarcinoma (20.00%) (P<0.01), and exhibited a rising trend with the differentiation degrees of tubular adenocarcinoma. nm23H(1) protein in MSI positive group was higher expressed (75%) than that in MSI negative group (45.45%, P<0.05).


CONCLUSIONS
The expression of ICAM-1 in lymphatic vessels is beneficial to the judgement of the invasion and metastasis ability of colon cancer and the anti-tumor immunity function, and shows an important clinical significance in predicting lymphatic metastasis of colon cancer. MSI and LOH may separately control the development of sporadic colon cancer with different pathways. LOH mostly arises in the late period of sporadic colon cancer and endows a high aggressive and poor prognostic phenotype. By compassion, MSI may be an early period molecule marker for sporadic colon cancer, enhanced expression of nm23H(1) protein can effectively inhibit colon cancer metastasis and improve prognosis of sporadic colon cancer patients.
Su
Zhi-Hong
ZH
Department of Histology and Embryology, Zhejiang University Medical College, Hangzhou 310031, Zhejiang Province, China.
Li
Ji-Cheng
JC
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002681:China; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; D018799:Intercellular Adhesion Molecule-1; D009701:Nucleoside-Diphosphate Kinase