Department of General Surgery, No. 3 People's Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
J Surg Res. 2011 Jun 15;168(2):188-96. doi: 10.1016/j.jss.2009.10.030. Epub 2009 Nov 11.
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.
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.
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→III(a) in 4 patients, III(a)→III(b) in 3 patients, and III(b)→IV in one patient). Survival analysis demonstrated that better prognosis in patients without LNM and/or LNMM.
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.
本研究旨在评估胃癌患者淋巴管生成、淋巴管侵犯(LVI)和淋巴结微转移(LNMM)的临床意义。
分析 LVI 免疫组化(IHC)染色(n=68)、LNMM(包括 CK20 和 CK 泛免疫染色,n=51)表达水平对临床病理特征和预后的影响。
LVI-IHC 阳性率与浸润深度更深(P=0.044)、TNM 分期较晚(P=0.003)、淋巴结转移(LNM)更广泛有关(P=0.000)。LVD 水平与静脉侵犯(P=0.037)、TNM 分期较晚(P=0.020)、LVI-HE 阳性(P=0.040)、LVI-IHC 阳性(P=0.001)和 LNM 更严重(P=0.001)有关。LVI 阴性组的生存情况明显优于 LVI 阳性组。LVD≥15/视野组的生存率明显低于 LVD≤14/视野组(P=0.032)。浸润深度、N 分期、LNM、血管侵犯或 LVI 是 3 年生存率的独立预后因素。HE 染色 LNM 患者的发生率从 74.5%(38/51)增加到 CK 免疫组化的 88.2%(45/51),从 32.0%(253/791)增加到 41.5%(328/791)(P=0.001)。LNMM 的增加与肿瘤直径更大(P=0.001)、浸润深度更深(P=0.018)、LNM(P=0.001)和更晚的 TNM 分期(P=0.012)、LVI 阳性(P=0.04)有关。同时,LNMM 的评估显示了淋巴结分期(N0→N1 期 7 例,N1→N2 期 6 例,N2→N3 期 1 例)和 TNM 分期(Ib→II 期 4 例,II→IIIa 期 4 例,IIIa→IIIb 期 3 例,IIIb→IV 期 1 例)的迁移。生存分析表明,无 LNM 和/或 LNMM 的患者预后较好。
本研究使用 D2-40 和 CK 抗体(包括 CK20 和 CK 泛抗体)进行免疫组化分析,在胃癌标本中检测到更高的 LVI 和 LNMs 发生率。本研究表明,淋巴管生成相关因素(如 LVI、LVD 和 LNMM)与患者术后预后密切相关。因此,这些因素的免疫组化评估可用于准确确定肿瘤侵袭性。