Color Doppler assessment of blood flow in endometrial cancer

Objective: To determine the location and intensity of angiogenesis as well as selected flow parameters by transvaginal color Doppler (TVCD) and to evaluate the relation of myometrial invasion, histological grading, lymph nodes, and omental and adnexal metastasis on blood flow characteristics in endometrial cancer.

Methods: Transvaginal colour Doppler and pulsed Doppler ultrasound were performed on 90 women with endometrial cancer. The degree of invasion as well as adnexal, omental, and pelvic lymph node metastasis was evaluated. Location of the blood vessels (peripheral, central, mixed) and vascular density as well as selected Doppler blood flow indices: PSV, RI of neoplastic infiltration was assessed.

Results: The median age of the 90 women was 63.3 +/- 12.3 years (range 32 to 86 years); of these 92.2% were postmenopausal. Cancer concerned only the endometrium (E), with superficial (S) and deep infiltration (D) established in 14.4%, 45.6% and 40%, respectively. The histological maturity was as follows: G1 - 17.6%, G2 - 66.7%, G3 - 16.6% of cases. Adnexal, omental and lymph node metastasis was found in 12.2%, 3.3% and 16.6%, respectively. Abnormal low impedance and high velocity flow (mean RI 0.38 +/- 0.09, PSV 20.45 +/- 9.6 cm/sec) were found in 88.9% of cases. In types E, S, D in 61.5%, 92.7% and 94.4%, respectively (p = 0.003). Differences in RI and PSV between groups with high and low vascular density were statistically significant (p = 0.005 and 0.001, respectively). In all cases peripheral and mixed vascularity were found more frequently (p < 0.05). A positive significant correlation between vascular density increase and surgicopathological stage of cancer was found more frequently (p < 0.005). There were significant differences in vascular density, Doppler blood flow indices and vascular location in each type of histological malignancy (p < 0.05). No significant differences in each flow parameter in hematogenous-adnexal/omental metastatic and non metastatic cases were found, whereas pelvic lymph node involvement and vascular density were shown to be statistically significant (p < 0.02). There were significant differences in vascular density in lymph-node positive cases whereas the remaining flow parameters did not differ.

Conclusions: These results suggest that TVCD evaluation of endometrial cancer is a reliable method for assessing endometrial angiogenesis. Our results indicate that blood flow rates correspond with increased angiogenesis in endometrial cancers, and might potentially be used as a good prediction factor for tumor progression and metastasis in affected women. Preoperative ultrasound examination should be seen as an important tool in the establishment of individualized treatment programs for women with endometrial cancer.

Doppler velocimetry; Endometrial cancer

[1] Folkman J.: "What is the evidence that tumors are angiogenesis dependent'?". J. Natl. cancer Inst. , 1990, 82, 4.

[2] Weidner N.: "The relationship of tumor angiogenesis and rnetastasis with emphasis on invasive breast cancer". In: "Advances in pathology". Chicago, Mosby-Year Book, 1995, 5, 101.

[3] Folkman J.: "Angiogenesis and breast cancer". J. Clin. Oneal., 1994, 12, 441.

[4] Sladkevicius P., Valentin L., Marsal K.: "Endornetrial thickness and Doppler velocimetry of the uterine arteries as discriminators of endornetrial status in women with postrnenopausal bleeding: a comparative study". Am. J. Obst. Gynecol., 1994, 171, 772.

[5] Bourne TH., Campbell S., Steer C.V., Royston P., Whitehead M.L, Collins W.P.: "Detection of endornetrial cancer by transvaginal ultrasonography with color flow imaging and blood flow analysis a preliminary report". Gynecol. Oneal., 1991, 40, 253.

[6] Alcazar J.L., Castillo G., Minguez J.A., Galan MJ.: "Endornetrial blood flow mapping using transvaginal power Doppler sonography in women with postrnenopausal bleeding and thickened endornetriurn" Ultrasound Obstet. Gynecol., 2003, 21, 583.

[7] Sheth S., Hamper U., McCollurn M.: "Endornetrial blood flow analysis in postrnenopausal women: can it help differentiate benign from malignant causes of endornetrial thickening'1". Radiology, 1995, 195, 661.

[8] Toi M., Kashitane J., Torninaga T.: "Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma" lnt. J. cancer, 1993, 55, 371.

[9] Folkmann J.: "Induction of angiogenesis during the transition from hyperplasia to neoplasia". Nature, 1989, 339, 58.

[10] Kirschner C.V., Alanis-Amezcua J.M., Martin V.G. et al.: "Angio-genesis factor in endornetrial carcinoma: a new prognostic indicator?". Am. J. Obstet. Gynecol., 1996, 174, 1879.

[11] Morgan K.G., Wilkinson N., Buckley C.H: "Angiogenesis in endometrial carcinoma". Int. J. Gynecol. Cance,; 1996, 6, 385.

[12] Tornos C., Silva E.G., El-Naggar A. et al.: "Aggressive stage I grade I endometrial carcinoma". Cancer, l 992, 70, 790.

[13] Abulafia O., Triest WE., Sherer D.M., Hansen C.C., Ghezzi F "Angiogenesis in endornetrial hyperplasia and Stage I endometrial carcinoma". Obstet. Gynecol., 1995, 86, 479.

[14] Lanciano R.M., Com B.W., Schultz D.J. et al.: "The justification for a surgical staging system in endometrial carcinoma". Radiother. Oncol., 1993, 28, 189.

[15] Artner A., Bosze P., Gonda G.: "The value of ultrasound m preoperative assessement of the rnyornetrial and cervical invasion in endometrial carcinoma". Gynecol. Oneal., 1994, 54, 147.

[16] Sawicki W., Spiewankiewicz B., Stelrnach6w J., Cendrowski K "The value of ultrasonography in preoperative assessment of selected prognostic factors in endornetrial cancer". Eur. J. Gynecol. Oneal., 2003, 24, 293.

[17] Folkman J.: "What is the evidence that tumors are angiogenesis dependent?". J. Natl Cancer Inst., 1990, 82, 4.

[18] Hanson M.B., Van Nagell J.R., P owell D.E. et al.: "The prognostic significance of lyrnphovascular space invasion in Stage I en dome trial cancer". Cancer, 1985, 55, 1753.

[19] Takeshima N., Hirai Y., Tanaka N. et al.: "P elvic lymph node metastasis in endometrial cancer with no myometrial invasion". Obstet. Gynecol., 1996, 88, 280.

[20] Weiner Z., Beck D., Rottem S., Brandes J.M., Thaler I.: "Utenne artery flow velocity waveforms and color flow imaging in women with perimenopausal bleeding". Acta Obstet. Gynecol. Scand., 1993, 72, 162.

[21] Ambros R.A., Kurman R.J.: "Combined assessment of vascular and myometrial invasion as a model to predict prognosis in Stage I endometrioid adenocarcinoma of the uterine corpus". Cancer, 1992, 69, 1424.

[22] Ozuysal S., Bigin T., Ozan H. et al.: "Angiogenesis in endometrial carcinoma: correlation with survival and clinicopathologic risk factors". Gynecol. Obstet. Invest., 2003, 55, 173.

[23] Ambrose R.A., Kurman R.J.: "Combined assessment of vascular and myometrial invasion as a model to predict prognosis in Stage I endometrioid adenocarcinoma of the uterine corpus". Cancer, 1992, 69, 1424.

[24] Brooks P.C., Montgomery A.M., Rosenfeld M. et al.: "Integnn alpha versus beta 3 antagomsts promote tumor regresSlon by mducing apoptosis of angiogenic blood vessels". Cell, 1994, 79, 1157.