Cheng W F, Lee C N, Chu J S, Chen C A, Chen T M, Shau W Y, Hsieh C Y, Hsieh F J
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei.
Cancer. 1999 Feb 1;85(3):651-7. doi: 10.1002/(sici)1097-0142(19990201)85:3<651::aid-cncr15>3.0.co;2-9.
The importance of angiogenesis now is well recognized. Conventionally, tumor angiogenesis is assessed by determination of microvessel density (MVD) in the surgical specimen. This study examines tumor angiogenesis using power Doppler ultrasound and a quantitative image processing system. The authors hope to develop an in vivo and noninvasive method for quantitating tumor angiogenesis.
Thirty-five patients with FIGO Stage IB-IIA cervical carcinoma exhibiting visible cervical tumors by transvaginal ultrasound were included in this study. All patients underwent radical abdominal hysterectomy and pelvic lymph node dissection. Transvaginal power Doppler ultrasound was performed before surgery to search for blood flow signals from the tumor. The intratumoral vascularity index (VI) and resistance index (RI) were calculated. The VI was defined as the number of colored pixels divided by the number of total pixels in the defined tumor section. Maximal VI and minimal RI of a certain tumor were used for analysis. Clinical and pathologic data also were recorded. The MVD of the excised tumor was assessed immunohistochemically using a monoclonal antibody against CD34.
Significantly higher VI values were noted in Stage II tumors compared with Stage 1 tumors (19.01+/-10.90% vs. 9.09+/-6.59%; P = 0.008), tumors invad-ing+/-50% of the cervical stroma compared with tumors invading < 50% of the cervical stroma (13.20+/-8.20% vs. 5.72+/-5.00%; P = 0.003), tumors with lymphovascular emboli compared with tumors without lymphovascular emboli (17.28+/-8.26% vs. 6.98 +/- 5.09%; P = 0.001), and tumors with pelvic lymph node metastases compared with tumors without pelvic lymph node metastases (26.16+/-7.88% vs. 8.00+/-4.95%; P = 0.021). None of the variables mentioned earlier showed a significant difference in terms of the RI values. No correlation was noted between intratumoral RI and VI in respective tumors (P = 0.53). Analysis of VI revealed linear regression with regard to tumor size (P < 0.001, correlation coefficient [r] = 0.586) and depth of stromal invasion (P = 0.002, r = 0.497). In addition, the MVD exhibited a linear relation with VI (P = 0.006, r = 0.454), tumor size (P = 0.005, r = 0.465), and depth of stromal invasion (P = 0.009, r = 0.436) using simple regression analysis. No correlation could be found between MVD and RI.
In cervical carcinoma, intratumoral VI assessment by power Doppler ultrasound and quantitative image processing system showed better correlation with tumor stage, tumor size, and pathologic findings including depth of stromal invasion, lymphovascular emboli, and pelvic lymph node metastases than intratumoral RI. The in vivo indicator of angiogenic activity (VI) is well correlated with the conventional indicator of tumor angiogenic activity (MVD). Thus, VI could be a useful parameter for the in vivo assessment of global tumor angiogenesis.
血管生成的重要性如今已得到充分认可。传统上,肿瘤血管生成是通过测定手术标本中的微血管密度(MVD)来评估的。本研究使用能量多普勒超声和定量图像处理系统来检测肿瘤血管生成。作者希望开发一种用于定量肿瘤血管生成的体内非侵入性方法。
本研究纳入了35例FIGO分期为IB-IIA期的宫颈癌患者,经阴道超声可显示宫颈肿瘤。所有患者均接受了根治性腹式子宫切除术和盆腔淋巴结清扫术。术前进行经阴道能量多普勒超声检查,以寻找肿瘤的血流信号。计算肿瘤内血管指数(VI)和阻力指数(RI)。VI定义为在定义的肿瘤区域内彩色像素数除以总像素数。取某一肿瘤的最大VI和最小RI进行分析。同时记录临床和病理数据。使用抗CD34单克隆抗体通过免疫组织化学方法评估切除肿瘤的MVD。
与I期肿瘤相比,II期肿瘤的VI值显著更高(19.01±10.90%对9.09±6.59%;P = 0.008);与浸润宫颈基质<50%的肿瘤相比,浸润宫颈基质±50%的肿瘤VI值更高(13.20±8.20%对5.72±5.00%;P = 0.003);有淋巴管栓子的肿瘤比无淋巴管栓子的肿瘤VI值更高(17.28±8.26%对6.98±5.09%;P = 0.001);有盆腔淋巴结转移的肿瘤比无盆腔淋巴结转移的肿瘤VI值更高(26.16±7.88%对8.00±4.95%;P = 0.021)。上述变量在RI值方面均未显示出显著差异。各肿瘤的肿瘤内RI与VI之间未发现相关性(P = 0.53)。VI分析显示与肿瘤大小呈线性回归关系(P < 0.001,相关系数[r]=0.586)以及与基质浸润深度呈线性回归关系(P = 错0.002,r = 0.497)。此外,使用简单回归分析,MVD与VI(P = 0.006,r = 0.454)、肿瘤大小(P = 0.005,r = 0.465)和基质浸润深度(P = 0.009,r = 0.436)均呈线性关系。未发现MVD与RI之间存在相关性。
在宫颈癌中,通过能量多普勒超声和定量图像处理系统评估肿瘤内VI,与肿瘤分期、肿瘤大小以及包括基质浸润深度、淋巴管栓子和盆腔淋巴结转移在内的病理结果的相关性,优于肿瘤内RI。血管生成活性的体内指标(VI)与肿瘤血管生成活性的传统指标(MVD)具有良好的相关性。因此,VI可能是用于体内评估整体肿瘤血管生成的一个有用参数。