Plum Patrick S, Warnecke-Eberz Ute, Dhaouadi Oulfa, Alakus Hakan, Drebber Uta, Metzger Ralf, Prenzel Klaus L, Hölscher Arnulf H, Bollschweiler Elfriede
Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
Institute of Pathology, University of Cologne, Cologne, Germany.
Histol Histopathol. 2015 Oct;30(10):1193-202. doi: 10.14670/HH-11-618. Epub 2015 Apr 14.
The aim of this study was to identify molecular markers predicting depth of tumor infiltration and presence of lymph node metastasis in early esophageal cancer.
Between 1996 and 2004, 67 patients with pT1 esophagus cancer underwent esophagectomy. Resected tumors and lymph nodes were analyzed by immunohistochemistry for tissue infiltration, lymph node metastasis (LNM), micrometastasis and extracapsular lymph node infiltration (ELNI). We focused on MMP-2 (matrix-metalloproteinase-2), TIMP-2 (tissue inhibitor of metalloproteinase-2), PIM-1 and survivin as the most promising marker candidates. The data was correlated with the patients' long term follow-up (median follow-up time 11.4 years).
We found 22 pT1a and 45 pT1b carcinomas. None of the mucosal carcinomas, but 58% (26 patients) of the submucosal carcinomas showed lymph node metastasis or micrometastasis. The rate of LNM positively correlated with the depth of tumor infiltration (23% LNM in sm1 tumors and 82% LNM in sm3 tumors). Low grade PIM-1 expression (<30%) was significantly associated with occurrence of LNM (p=0.034) while high expression TIMP-2 (>70%) were detected in submucosal tumors. Logistic regression analysis revealed PIM-1 and Grading G3 as independent risk factors for LNM (p<0.001). Survival of patients with micrometastasis was comparable to those with LNM (median survival: 5.05 years versus 5.52 years). Patients with ELNI had the worst prognosis (median survival: 1.7 years).
PIM-1 is a promising marker for prediction of lymph node metastasis in early esophagus cancer. Extracapsular lymph node infiltration has an independent worse prognostic impact.
本研究旨在确定预测早期食管癌肿瘤浸润深度和淋巴结转移情况的分子标志物。
1996年至2004年间，67例pT1期食管癌患者接受了食管切除术。对切除的肿瘤和淋巴结进行免疫组织化学分析，以检测组织浸润、淋巴结转移（LNM）、微转移和包膜外淋巴结浸润（ELNI）。我们重点关注MMP-2（基质金属蛋白酶-2）、TIMP-2（金属蛋白酶组织抑制剂-2）、PIM-1和生存素作为最有前景的标志物候选物。数据与患者的长期随访结果（中位随访时间11.4年）相关。
我们发现22例pT1a癌和45例pT1b癌。黏膜癌均未发生淋巴结转移或微转移，但58%（26例患者）的黏膜下癌出现了淋巴结转移或微转移。LNM发生率与肿瘤浸润深度呈正相关（sm1肿瘤中LNM发生率为23%，sm3肿瘤中为82%）。低级别PIM-1表达（<30%）与LNM的发生显著相关（p=0.034），而在黏膜下肿瘤中检测到高级别TIMP-2表达（>70%）。逻辑回归分析显示PIM-1和G3分级是LNM的独立危险因素（p<0.001）。微转移患者的生存率与有LNM的患者相当（中位生存期：5.05年对5.52年）。有ELNI的患者预后最差（中位生存期：1.7年）。
PIM-1是预测早期食管癌淋巴结转移的一个有前景的标志物。包膜外淋巴结浸润具有独立的不良预后影响。
