TY - JOUR
T1 - Myometrial invasion and lymph node metastasis in endometrioid carcinomas: Tumor-associated macrophages, microvessel density, and HIF1A have a crucial role
AU - Espinosa, Inigo
AU - José Carnicer, Maria
AU - Catasus, Lluis
AU - Canet, Belén
AU - Dangelo, Emanuela
AU - Zannoni, Gian Franco
AU - Prat, Jaime
PY - 2010/11/1
Y1 - 2010/11/1
N2 - Myometrial invasion is an independent prognostic parameter of the endometrioid carcinomas which correlates with the risk of metastasis to pelvic and/or paraaortic lymph nodes. Recognition of myometrial invasion is sometimes difficult. In fact, myoinvasion is overdiagnosed in routine practice in as many as 25% of the cases. Recently, it has been observed that tumor-associated macrophages stimulate angiogenesis and promote cancer dissemination. Tumor macrophages (CD163), microvessel density (CD31), and hypoxia inducible factor 1 α subunit (HIF1A) were investigated in 64 primary endometrioid carcinomas with (50 cases) and without (14 cases) myometrial invasion as well as in the corresponding regional lymph nodes metastases of 20 of the myoinvasive tumors. Endometrioid carcinomas with myometrial invasion showed higher number of CD163-tumor macrophages and greater microvessel density than endometrioid carcinomas without myometrial invasion (P=0.000 and P=0.000, respectively). In carcinomas confined to the corpus uteri (stage I), expression of HIF1A was associated with deep myoinvasion (stage IC) (P=0.006). There was a significant relationship between microvessel density and CD163-macrophages both in the myoinvasive and nonmyoinvasive tumors. On the other hand, high-grade endometrioid carcinomas had more macrophage infiltrates and microvessels than low-grade tumors (P=0.03 and P=0.07). Also, there was a positive correlation between CD163-macrophages and microvessel density in the primary tumors and their corresponding regional lymph node metastases. These findings link increased microvessel proliferation to stromal macrophage infiltrate and suggest that enhanced tumor angiogenesis, triggered by stromal macrophages, regulates the progression of endometrioid carcinomas. The identical stroma microenvironment found in the primary and the corresponding metastatic tumor suggests that tumor stroma response is determined by the intrinsic biology of the tumor. © 2010 by Lippincott Williams & Wilkins.
AB - Myometrial invasion is an independent prognostic parameter of the endometrioid carcinomas which correlates with the risk of metastasis to pelvic and/or paraaortic lymph nodes. Recognition of myometrial invasion is sometimes difficult. In fact, myoinvasion is overdiagnosed in routine practice in as many as 25% of the cases. Recently, it has been observed that tumor-associated macrophages stimulate angiogenesis and promote cancer dissemination. Tumor macrophages (CD163), microvessel density (CD31), and hypoxia inducible factor 1 α subunit (HIF1A) were investigated in 64 primary endometrioid carcinomas with (50 cases) and without (14 cases) myometrial invasion as well as in the corresponding regional lymph nodes metastases of 20 of the myoinvasive tumors. Endometrioid carcinomas with myometrial invasion showed higher number of CD163-tumor macrophages and greater microvessel density than endometrioid carcinomas without myometrial invasion (P=0.000 and P=0.000, respectively). In carcinomas confined to the corpus uteri (stage I), expression of HIF1A was associated with deep myoinvasion (stage IC) (P=0.006). There was a significant relationship between microvessel density and CD163-macrophages both in the myoinvasive and nonmyoinvasive tumors. On the other hand, high-grade endometrioid carcinomas had more macrophage infiltrates and microvessels than low-grade tumors (P=0.03 and P=0.07). Also, there was a positive correlation between CD163-macrophages and microvessel density in the primary tumors and their corresponding regional lymph node metastases. These findings link increased microvessel proliferation to stromal macrophage infiltrate and suggest that enhanced tumor angiogenesis, triggered by stromal macrophages, regulates the progression of endometrioid carcinomas. The identical stroma microenvironment found in the primary and the corresponding metastatic tumor suggests that tumor stroma response is determined by the intrinsic biology of the tumor. © 2010 by Lippincott Williams & Wilkins.
KW - angiogenesis
KW - HIF1A
KW - lymph node metastases
KW - myometrial invasion
KW - tumor-associated macrophages
U2 - 10.1097/PAS.0b013e3181f32168
DO - 10.1097/PAS.0b013e3181f32168
M3 - Article
VL - 34
SP - 1708
EP - 1714
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
SN - 0147-5185
IS - 11
ER -