[Lymph node micrometastases and expression of metastasis-related gene proteins in patients with colorectal cancer].
OBJECTIVE
To study lymph node micrometastases (LNMM), expression of nm23-H(1), MMP(9), TIMP(2) proteins, and their relationship and clinical significance in patients with stage Dukes B colorectal cancer.


METHODS
Thirty patients with stage Dukes B colorectal cancer were studied. LNMM in these patients was detected by immunohistochemical anti-cytokeratin 20 (CK20) staining. The expression of nm23-H(1), MMP(9) and TIMP(2) proteins in primary tumors was examined by Strept-avidin-biotin complex method. Clinical-pathological data and survival of each patient were recorded and analyzed.


RESULTS
(1) The positive dyeing of CK20 was observed in 26.7% for cases and in 7.8% for lymph nodes of 30 patients with stage Dukes B colorectal cancer. (2) Different expression of nm23-H(1) and MMP(9) proteins in the patients between stage Dukes B and stage Dukes CD was observed (P < 0.05). The decreased nm23-H(1) expression, and/or the increased MMP(9) expression in primary stage Dukes B tumors were significantly associated with LNMM (P < 0.05). Sensitivity and specificity for detection of LNMM by using nm23-H(1) or MMP(9) were respectively 62.5% and 81.8% or 75.0% and 69.8%. If by combining nm23-H(1) with MMP(9), specificity for detection of LNMM became 90.9%. The expression of TIMP(2) protein was not related with stage Dukes and LNMM. (3) The percent of tumor recurrence and/or metastasis for the stage Dukes B patients with LNMM was significantly higher than that for the patients without LNMM (P < 0.05), but the survival percent for the patients with LNMM was significantly lower than that for the patients without LNMM. The outcome for the patients with nm23-H(1) (-) LNMM (+) or MMP(9) (+) LNMM (+) was significantly worse than that for patients with nm23-H(1) (+) LNMM (-) or MMP(9) (+) LNMM (-) (P < 0.05).


CONCLUSIONS
LNMM is detected by immunohistochemical anti-CK20 staining. The expression of nm23-H(1) and MMP(9) in primary stage Dukes B tumors was significantly associated with LNMM. The outcome in the LNMM patients with nm23-H(1) (-) and/or MMP(9) (+) were worse. Combining examination of CK20 for lymph nodes with expression of nm23-H(1) and MMP(9) for primary tumors is of important clinical significance for staging of Dukes, selection of adjuvant treatment and evaluation of prognosis in patients with colorectal cancer.
Fan
Yue-zu
YZ
Department of Surgery, Tongji Hospital of Tongji University, Shanghai 200065, China. fanyuezu_shtj@msn.com
Li
Xin-ping
XP
Liu
Wen-fang
WF
Li
Guang-ming
GM
D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*; D011379:Prognosis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D054778:NM23 Nucleoside Diphosphate Kinases; D019714:Tissue Inhibitor of Metalloproteinases; D007633:Keratins; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020780:Matrix Metalloproteinase 9