Clinical implications of expression of interleukin-8 related to myometrial invasion with angiogenesis in uterine endometrial cancers.
BACKGROUND
Angiogenesis is essential for development, growth and advancement of solid tumors. The tumor-associated macrophage has been recognized among inflammatory cells as a candidate for supplying tumor angiogenic factors. Interleukin (IL)-8 is assumed to be a macrophage-derived mediator of angiogenesis. This prompted us to study the clinical implications of macrophage-derived angiogenesis in uterine endometrial cancers.


METHODS
Sixty patients underwent curative resection for uterine endometrial cancers. The patient prognosis was analyzed with a 48 month survival rate after curative resection. In tissue of uterine endometrial cancers, the levels of IL-1alpha, IL-1beta, tumor necrosis factor-alpha, IL-8, basic fibroblast growth factor, vascular endothelial growth factor and platelet-derived endothelial cell growth factor were determined by enzyme immunoassay, and the localization and counts of microvessels and macrophages were determined by immunohistochemistry.


RESULTS
There was a significant correlation between microvessel counts and IL-8 levels and between infiltrated macrophage counts and IL-8 levels in uterine endometrial cancers. Immunohistochemical staining revealed that the localization of IL-8 was similar to that of CD68 for macrophages. IL-8 levels were significantly increased during myometrial invasion from stage Ia to stages Ib through IV.


CONCLUSIONS
IL-8 might act as an angiogenic switch in myometrial invasion in stage I uterine endometrial cancers. Furthermore, IL-8 supplied from infiltrated macrophages within and around the tumor might not be a prognostic indicator of advancement, but may be associated with myometrial invasion in uterine endometrial cancers.
Fujimoto
J
J
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan. jf@cc.gifu-u.ac.jp
Aoki
I
I
Khatun
S
S
Toyoki
H
H
Tamaya
T
T
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
D016207:Cytokines; D006133:Growth Substances; D016209:Interleukin-8; D009363:Neoplasm Proteins