LUDEC Study - Pilot Study of the Lavage of the Uterine Cavity for the Diagnosis of Endometrial Carcinoma

Endometrial Carcinoma (EC) - carcinoma of the lining of the uterus - is the most common gynecologic malignancy in western civilized countries. Just in the US, approximately 42,160 cases are diagnosed and 7,780 deaths occur annually.

Type I EC is estrogen-dependent and associated with conditions that elevate estrogen levels. The precursor lesion, atypical endometrial hyperplasia, is well described. Type I EC, often of endometroid histology, well differentiated in most cases, is usually diagnosed at an early stage due to irregular bleeding and therefore has a good prognosis.

Type II EC is not estrogen-dependent and of serous or clear cell histology. In contrast to type I cancers, the vast majority, especially of serous cancers, are high grade, affect postmenopausal women, do not cause early symptoms, are diagnosed at an advanced stage, behave more like epithelial ovarian cancer (EOC) and have a very poor prognosis. Precursor lesions in the endometrium are referred to as "serous endometrial intraepithelial carcinoma" (SEIC), lesions quite similar to the precursor lesion of EOC in the fallopian tube, called "serous tubal intraepithelial carcinoma" (STIC).

Unfortunately, most patients with type II epithelial EC, in particular the serous and clear cell carcinomas, experience few or no symptoms until the disease has metastasized. The lack of early symptoms and the absence of a reliable screening test to detect the disease early, result in women being diagnosed after the disease has spread beyond the uterus and therefore has a poor prognosis. For these reasons, there is a clear medical need for earlier diagnosis of type II EC.

Type I and type II uterine tumors also appear to have a different pattern of molecular alterations that underlie pathogenesis and/or progression (1). Alterations in the tumor suppressor gene PTEN, microsatellite instability, and K-ras alterations have been associated with the early development of type I tumors, while these alterations are uncommon in type II cancers. On the other hand, mutations in the TP53 gene appear to be important in the early pathogenesis of uterine serous carcinomas. Moreover, HER2 overexpression/amplification has been associated with type II tumors.