Development of Antibody Cocktail and Antibody Microarray for the Screening of Endometrial Cancer and Its Precursors (I)

Endometrial cancer is a common malignancy of the female genital tract with uprising incidence and motality worldwide. In the United States, the number of newly developed endometrial cancer case exceeded the sum of cervical cancer and ovarian cancer. In Taiwan, 30.8% increase in the incidence of endometrial cancer occurred during 2002-2006. Tool for the screening of endometrial cancer and its precursors has not yet available and is much urgent than years ago. Endometrial cancer has been categorized into 2 types; 80% of endometrial cancers are endometrioid carcinoma histologically and frequently occurs in the peri-menopausal age. The precursors are often preceded 3-4 years before the diagnosis of cancer, which represent a stepwise alternation in genomic expression and morphological appearance. Carcinogenesis begins long before any histologically distinguishable lesion such as atypical endometrial hyperplasia follows. Medical treatment may reverse the early endometrial alternation should the alternation be detected. Atypical endometrial hyperplasia (AEH), are pre-cancerous lesions and are often combined with endometrial cancer. Differentiation between AEH and endometrial carcinoma is clinically critical, but precise differentiation of AEH and endometrioid carcinoma may exceed the limitation of morphological observation under traditional histopathological stain. Molecular markers, adjunctive to conventional histopathology, can be a resolution if available. Moreover, with the ease of collecting endometrial fluid and superficial endometrial tissue, sensitive antibodies can be used as a way to identify subtle molecular change that exists before the cellular of histologic change. The carcinogenesis can then be halted by medical management and life style modification. With the advent of proteomics, we propose to the development of diagnostic tools for the early detection of endometrial precancerous changes and also tools for the differentiation of AEH and carcinoma. Along with the diagnostic tool, we also propose to develop a kit for “endometrial smear”, for collecting endometrial fluid for ELISA and endometrial cells for cytohistologic study. A comprehensive test flow, including sample collection, preparation, staining and interpretation to achieve the aforementioned goals will be established and verified in this project. Based on Taiwan Gynecologic Oncology Group, a national-wide study group composed of gynecologic oncologists and gynecologic pathologists, large scale study for verification of its clinical efficacy can be impossible. More specifically, our goals are: More specifically, the goals are to develop and verify for clinical usage of diagnostic devices which consist (1) kit for sample collection (2) antibodies for identification of representative carcinogenesis marker and (3) interpretation standard, as an adjunctive tool, along with histopathological study, for (a) the differential diagnosis of endometrial hyperplasia in different grades and endometrial cancer; (b) risk assessment of emerging endometrial pre-cancerous lesion and endometrial cancer in women; (c) prediction of endometrial evolution after medication for endometrial hyperplasia. These tools offer a less invasive, alternative diagnostic tool other than traditional dilatation and curettage and can be clinical applied world-wide for the general use of detecting early molecular change and for the specific purpose of differentiating endometrial lesions, according to the targeted markers employed in the specific test.

Project ID:PC10008-0587
External Project ID:NSC100-2325-B182-008