Study on Lymph Node Metastasis Correlated to Lymphangiogenesis, Lymphatic Vessel Invasion, and Lymph Node Micrometastasis in Gastric Cancer

Background. This study aimed to evaluate the clinical significance of lymphangiogenesis, lymph vessel invasion (LVI), and lymph node (LN) micrometastasis (LNMM) in patients with gastric cancer. Methods. The influences of the expression levels of LVI, lymph vessel density (LVD) by D2-40 immunohistochemical (IHC) staining (n = 68), LNMM (including CK 20 and CK pan immunostainings, n = 51) on the clinicopathologic profiles and the prognosis were analyzed. Results. The higher positive rate of LVI-IHC was related to deeper invasion (P = 0.044), later TNM stage (P = 0.003), and more extensive LN metastasis (LNM, P = 0.000). The level of LVD was significantly associated with venous invasion (P = 0.037), later TNM stage (P = 0.020), positive LVI-HE (P = 0.040), positive LVI-IHC status (P = 0.001), and severer LNM (P = 0.001). Better prognosis in LVI negative group than LVI positive group has been identified. The survival rate of the group with LVD >= 15/field was significantly lower than that in the group with LVD <= 14/field (P = 0.032). Invasion depth, N stage, LNM, blood vessel invasion, or LVI was respectively an independent prognostic factor to 3-y survival rate. The incidence of patients with LNM and metastasized LNs increased respectively from 74.5% (38/51) by HE staining to 88.2% (45/51) by CK immunostaining and from 32.0% (253/791) to 41.5% (328/791) (P = 0.001). The increment of LNMM was correlated to larger tumor diameter (P = 0.001), deeper invasion (P = 0.018), LNM (P = 0.001) and later TNM stage (P = 0.012), positive LVI (P = 0.04). Meanwhile, the evaluation on LNMM revealed the migration of LN stage (N-0 -> N-1 in seven patients, N-1 -> N-2 in six patients, and N-2 -> N-3 in one patient), and TNM stage (I-b -> II in four patients, II -> IIIa in 4 patients, IIIa -> IIIb in 3 patients, and IIIb -> IV in one patient). Survival analysis demonstrated that better prognosis in patients without LNM and/or LNMM. Conclusion. Our immunohistochemical analyses using antibodies of D2-40 and CK, including both CK 20 and CK pan, detected a higher incidence of LVIs and LNMs in gastric cancer specimens. This study shows close correlations among lymphangiogenesis related factors, such as LVI, LVD, and LNMM, and patients' prognosis after surgery. Therefore, immunohistochemical evaluations of these factors could be used for the accurate determination of tumor aggressiveness. (C) 2011 Elsevier Inc. All rights reserved.