Proliferative activity of early ovarian clear cell adenocarcinoma depends on association with endometriosis.
OBJECTIVE
To investigate differences in the biological characteristics of ovarian clear cell adenocarcinoma based on the presence/absence of endometriosis and tumor proliferative activity.


METHODS
Stage I ovarian clear cell adenocarcinoma patients were divided into groups with and without endometriosis, and immunohistochemical expression of proliferating cell nuclear antigen was determined in surgical specimens. Then xenograft models of human ovarian clear cell adenocarcinoma with or without human ectopic endometrium were created in severe combined immunodeficiency mice, and tumor growth was assessed from the wet weight and the bromodeoxyuridine uptake. Furthermore, a xenograft model of human endometriosis was made with or without ovarian clear cell adenocarcinoma and cytokine production was investigated.


RESULTS
The proliferating cell nuclear antigen labeling index was significantly lower in the tumors of patients with endometriosis compared to the tumors of patients without endometriosis. In tumor-bearing mice, the tumor weight and bromodeoxyuridine uptake were both significantly lower when ovarian clear cell adenocarcinoma was associated with endometriosis than in its absence. Release of transforming growth factor-beta1 and interleukin-6 from the ectopic human endometrium was greater in the presence of clear cell adenocarcinoma than without it, and transforming growth factor-beta1 levels showed a significant difference.


CONCLUSIONS
The proliferative activity of early ovarian clear cell adenocarcinoma seems to depend on the association of this cancer with endometriosis. When endometriosis is associated with ovarian clear cell adenocarcinoma, there is a change of its cytokine production that may inhibit tumor growth.
Komiyama
Shin-Ichi
S
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. komiyama@fujita-hu.ac.jp
Aoki
Daisuke
D
Katsuki
Yukio
Y
Nozawa
Shiro
S
D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D004715:Endometriosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015850:Interleukin-6; D018809:Proliferating Cell Nuclear Antigen; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001973:Bromodeoxyuridine