胃腺癌磁共振扩散加权成像表观弥散系数与分子标记物Ki-67的相关性分析

Correlation of MRI apparent diffusion coeffcient with molecular marker Ki-67 in gastric cancer

目的通过测定胃癌磁共振扩散加权成像表观弥散系数（ADC）与肿瘤细胞免疫组织化学（免疫组化）Ki-67表达的相关性，探讨应用ADC值从分子水平诊断胃癌恶性程度的价值。方法对2014年11月至2015年8月于浙江中医药大学附属第一医院行MRI检查并接受根治性手术的87例胃癌患者进行回顾性队列分析，全组患者均经术后组织标本病理检查证实为胃癌。将MRI结果与术后常规病理免疫组化Ki-67检测结果进行相关性分析。结果胃癌在MRI上表现为不规则增厚．增强扫描肿瘤呈不均一强化。胃癌组织在DWI上（b=800s／ram。）图像上呈高信号，正常胃壁呈等信号：胃癌患者胃壁的ADC图像上肿瘤为（1．114±0．265）×10^-3mm^2／s，低于正常胃壁的ADC值（2．032±0．202）×10^-3mm^2／s，差异有统计学意义（￡=26．209，P=0．000）。高分化和中分化胃癌、中．低分化胃癌、低分化胃癌、印戒的细胞癌和黏液腺癌的ADC值分别为（1．347±0．234）×10^-3mm^2／s、（1．179±0．257）×10～mm^2／s、（0．996±0．185）×10^-3mm^2／s、（1．082±0．230）×10^-3mm^2／s，差异有统计学意义（F=8．498，P=0．000）。随着胃癌肿瘤组织Ki．67表达增加，其ADC值降低，胃癌ADC值与Ki-67表达程度呈负相关（r=-0．570，P=0．000）；且进一步根据胃癌的分化程度不同进行分组发现，高一中分化（r=-0．627，P=0．016）、低分化（r=-0．787，P=0．000）以及印戒细胞和黏液腺癌（r=-0．792，P：0．000）与Ki-67的表达水平均呈为负相关，而中．低分化胃癌的ADC值与Ki-67表达水平的相关性并无统计学意义（均P〉0．05）。结论胃癌ADC值能从分子水平反映细胞增殖程度，高ADC值提示Ki．67低表达。胃癌ADC值可从分子水平为胃癌术前恶性程度的判断及预后评估提供参考。

Objectives To study the correlation between MRI apparent diffusion coefficient （ADC） and expression of Ki-67 in gastric cancers, and to investigate the application of ADC value in diagnosing the malignanee of gastric cancer. Methods A retrospective cohort analysis was performed on 87 gastric cancer patients who received MRI examination and radical resection at Zhejiang Provincial Hospital of Traditional Chinese Medicine from November 2014 to August 2015. All the postoperative resected samples were confirmed as gastric cancer. Preoperative MRI examination was performed by using Siemens 3.0-T Verio MRI with following parameters： section thickness 3 ram, gap 1 ram, matrix 182 x 320, field of view 40 cm. Plain scan was followed by Tl-weighted fat suppression technique VIBE 3D （TR3.92/TE1.39,90~） scans at arterial phase （the 30th second）, portal venous phase （the 60th second）, lag period （the 90th second）, axial planes and coronal planes （the 180th second）, and sagittal planes （the 210th second）, respectively. ADC value of tumor was measured at b-factor of 800 s/mm~ and ADC map was generated from DWI data on the work station. The expression of Ki-67 in cancer tissue was detected by routine immunohistochemical （SP） staining after surgery. Correlation between ADC value and the expression of Ki-67 in gastric cancer was analyzed. Results Irregular thickening of the gastric wall and inhomogeneous enhancement of the tumor after injection of the contrast material appeared in gastric cancer. Gastric cancer tissue presented hyperintensity and normal gastric wall presented isointensity in DWI image （b = 800 s/ram2）. Compared with normal gastric tissue, mean ADC value of gastric cancer tissue was significant lower [（1.114 ＋ 0.265） × 10^-3 mm^2/s vs. （2.032± 0.202） × 10^-3 mm^2/s, t = 26.209, P = 0.0001. The ADC values of high-middle differentiation group, middle-low differentiation group, low differentiation group and signet ring cell carcinoma/mucinous adenocarcinoma group were （1.347 _＋ 0.234） × 10^-3 mm^2/s, （1.179 ± 0.257） ×10^-3 mm^2/s, （0.996 ± 0.185） xl0-3 mm^2/s and （1.082 -＋ 0.230） xl0-3 mm：/s, respectively. The difference of mean ADC value among different tumor stages was significant（F = 8.498, P= 0.000）. Along with the Ki-67 expression up-regulated, the ADC value decreased in cancer tissue. The Ki-67 expressions in cancer tissue was negatively correlated with cancer ADC values （r = -0.570, P--0.000）. Furthermore, negative correlations of Ki-67 expressions with ADC values of high-middle differentiation group （r =-0.627, P = 0.016）, low differentiation group （r =-0.787, P = 0.000） and signet ring cell carcinoma/mucinous adenocarcinoma group （r = -0.792, P = 0.000） were observed respectively, while Ki-67 expression was not correlated with ADC value of middle-low differentiation group. Conclusion The ADC value of gastric cancer can reflect the level of tumor differentiation, and is negatively correlated with Ki-67 expression in cancer tissues.