Endometrial DNA Content In Relation To Diagnosis & Prognosis Of Endometrial Hyperplasia

Endometrial hyperplasia is a proliferative disorder characterised by a wide spectrum of architectural and cytological changes of the glands and stroma. It is a consequence of excessive or unopposed estrogen exposure obesity, polycystic ovarian syndrome with chronic an ovulation and estrogen producing tumors, ovarian stromal tumors and estrogen only replacement therapy are all associated with increase risk of endometrial hyperplasia and/ or endometrial carcinoma. The current classification system for endometrial hyperplasia (WHO) divided it into two broad categories; hyperplasia without cytological atypia and hyperplasia with cytologic atypia. These categories are further subdivided into simple or complex according to architectural features. This nomenclature has prognostic importance: in up to 23% of patients with atypical hyperplasia, the hyperplasia progresses to carcinoma, whereas in only 2% of patients with hyperplasia without atypia, the hyperplasia progresses to carcinoma.Cytologic atypia is the only important morphologic feature that detect endometrial lesions with invasive potentially.Risk of invasive cancer increased with cytologic atypia, the progression is slow and takes many years.This study was conducted from April 2004 to April 2006 and included (100) patients with median age of 48.5 years complaining of abnormal vaginal bleeding diagnosed as simple endometrial hyperplasia (n = 49), complex hyperplasia (n = 28) atypical hyperplasia (n = 14), endometrial adenocinoma (n = 9) after confirmed histopathologically either by fractional curettage and biopsy or from hysterectomy specimens.The aim of this work is to measure the nuclear DNA content (ploidy pattern) and cell cycle kinetics (S.Phase fraction and proliferation fraction) of different types of endometrial hyperplasia by image cytometry and to assess if image cytometry can distinguish different categories of endometrial hyperplasia to select the high risk women who will need strict follow up surveillance.DNA ploidy of the majority of nonatypical endometrial hyperplasia were diploid pattern with DNA index ranging from (1-1.14) but high percent of atypical endometrial hyperplasia and all endometrial adenocarcinoma cases were aneuploid with DNA index ranging from (1.3-1.5).Cell cycle kinetics (S. Phase fractions and proliferation index) were high in atypical hyperplasia compared to non atypical hyperplasia and these difference were of statistical significance; and highly significance in endometrial adenocarcinoma cases compared to nonatypical hyperplasia cases.This study showed that endometrial hyperplasia may be divided into two main categories irrespective histopathological pattern.1- Endometrial hyperplasia with normal DNA pattern (diploid) and normal cell cycle kinetics this type is most probably non progressing and can be managed conservatively.2- Endometrial hyperplasia with aneuploid pattern and/ or abnormal cell cycle kinetics this type is mostly progressive irrespective histopathological examinationWe concluded that the study of DNA content and cell cycle kinetics by image cytometry might help in picking up, among all women with endometrial hyperplasia, the group of patients who need further close and strict follow up by endometrial histopathologic study. This is going to minimize the cost and invasiveness of surveillance of patients with various grades of endometrial hyperplasia.Finally: Single cell DNA cytometry is a useful tool in the differential diagnosis of endometrial lesions that could be used as a complementary diagnostic method especially in histomorpholoigcally difficult cases. A long term studies are required to support the role of high S. Phase fraction and PI as a predictor for possible development of atypical hyperplasia or endometrial adenocarcimona; additional studies should include morphometric analysis in order to improve the usefulness of image analysis in differential diagnosis of endometrial lesions.Recommendation:Long term studies on Large number of cases with larger sample size and longe duration of follow up are needed to evaluate the prognostic value of cell cycle kinetics (S. Phase fraction and proliferation index) in endometrial hyperplasia cases.The combination of molecular, morphometrical and clinical out come data offers a highly standardized therapeutic decision making process and reduce the frequency of over and under treatment of diseased endometria.