Interferon regulatory factor-1 (IRF-1) suppression and derepression during endometrial tumorigenesis and cancer progression.
Interferon regulatory factor-1 (IRF-1) is a tumor suppressor gene presumed to be involved in the control of cellular proliferation and transformation. Given that the IRF-1 is consistently expressed in the normally cycling endometrium, the question was raised of the possible role of IRF-1 in the genesis of endometrial adenocarcinoma. A series of 25 normal and 86 malignant endometria was investigated using immunohistochemical techniques and the anti-IRF-1 polyclonal antibody c-20. Normal endometrial glands were, indeed, consistently reactive with IRF-1. Excluding the invading tumor front, malignant endometria were deprived of IRF-1 reactivity, as 81 of the 86 cases (94.2%) were negative for this antigen. At the invading tumor front, however, IRF-1 was derepressed in tumor cells in 35% of the cases. This phenomenon was independent of the extent of lymphocytic response, but it was associated with thymidine phosphorylase (TP) expression. Furthermore, TP up-regulation and host's lymphocytic response in the area were directly associated. IRF-1 derepression by invading tumor cells was associated with poor prognosis, independently of FIGO stage. It is concluded that down-regulation of IRF-1 is a constant finding in endometrial tumorigenesis. However, derepression of IRF-1 may occur in a subset of tumors, and this event is associated with TP up-regulation and aggressive tumor behavior.
Giatromanolaki
Alexandra
A
Department of Pathology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Koukourakis
Michael I
MI
Ritis
Konstantinos
K
Mimidis
Konstantinos
K
Sivridis
Efthimios
E
D000230:Adenocarcinoma / Q000201:enzymology / Q000209:etiology / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D050856:Interferon Regulatory Factor-1; D015999:Multivariate Analysis; D010750:Phosphoproteins / Q000378:metabolism*; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D013939:Thymidine Phosphorylase