Basic helix-loop-helix (bHLH) DNA-binding proteins have been reported to regulate tissue-specific transcription of cellular differentiation within multiple cell lineages. The Id family of helix-loop-helix proteins does not possess a basic DNA-binding domain and functions as a negative regulator of bHLH proteins by forming high-affinity heterodimers with bHLH proteins. Id proteins were originally characterized as inhibitors of DNA binding and cell differentiation. Thus, overexpression of Id proteins correlates with cell proliferation and arrested differentiation in many cell lineages. To elucidate the involvement of Idl in endometrial carcinogenesis, we analyzed serial frozen sections for Idl protein expression in 20 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of Idl-stained cells and the patient's characteristics, including histological grade, clinical stage, presence of invasion to > 1/2 myometrium, and clinical outcome. In normal endometria, Idl was not detected in either the proliferative or the secretory phase. There was, however, abundant Idl immunoreactivity in the endometrial carcinoma cells. Moreover, Idl was strongly expressed in the inflammatory cells. Scoring on the basis of the percentage of positive cells indicated that Idl expression is significantly associated with histological grade (P < 0.05) and the presence of invasion to > 1/2 myometrium (P < 0.05). Our results demonstrate that increased Idl expression in endometrial carcinoma correlates with the malignant potential of this tumor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.