Patients with endometrial cancer and more than 50% myometrial invasion on gross visual intraoperative estimation are at marked risk for extrauterine metastases, including pelvic and para-aortic lymph node metastases. Such patients should be considered for more aggressive surgical staging, including pelvic and para-aortic lymphadenectomy.

The differentiation of proadipocytes in vitro typically required prolonged culture of cells at a high density in high concentrations of serum and added hormones. With such culture conditions it is difficult to design experiments to determine the mechanisms that control the differentiation process. We now describe the rapid and parasynchronous growth arrest and differentiation of low density murine proadipocytes in heparinized medium containing only human plasma. When low density cells are cultured under these conditions, growth arrest at a distinct state in the G1 phase of the cell cycle occurs within 2 d and the differentiation of 80-100% of the cell population occurs within 4 d thereafter. The factors in human plasma which promote growth arrest and differentiation are heat labile and can be separated by barium adsorption. In the following paper we have used these methods to show that there are five separate phases which regulate the coupling of proadipocyte growth arrest and differentiation. The data reported in this paper establish that: (a) high cell density and extensive cell-to-cell contact are not required for adipocyte differentiation, (b) prolonged culture is not required for adipocyte differentiation, and (c) high concentrations of serum and/or added hormones are not required for adipocyte differentiation.Cell differentiation is a biological process that results in the expression of stable phenotypic changes in cells. Cell differentiation is typically preceded by growth arrest in the G1 phase of the cell cycle. For example, in vitro proadipocytes (8,9,25,26) and myoblasts (22) growth arrest in GE several days before the expression of the differentiated phenotype. In vivo, the differentiation of erythrocyte precursors (18) and epithelial precursor cells of the skin (16) also occurs in association with a loss in proliferative capacity and growth arrest in the GE phase of the cell cycle.The in vitro growth arrest of undifferentiated cells at G1 states induced by the deprivation of growth factors or nutrients has previously been suggested to be critically important in the physiological regulation of cell proliferation (2, 23, 29). There is, however, a paucity of data to support the conclusion that deprivation of growth factors or specific nutrients actually influences the control of proliferation of most stem cells in vivo. The control of cell proliferation mediated by the coupling of GL growth arrest and differentiation appears to be physiologically more relevant (16,18). We have, therefore, studied 394 the mechanisms that control the coupling of proadipocyte growth arrest and differentiation. We reported that the coupling process in proadipocytes is mediated at a distinct state in the GE phase of the cell cycle, designated Go (26). Attempts to delineate in more detail the events that control the coupling process have, however, been limited by technical difficulties. This is so because the induction of adipocyte differentiation by standard methods requires the culture of cells to be at a high den...

Dilation and curettage was more accurate in identifying hysterectomy tumor grade and less likely to miss a higher-grade tumor than was Z-sampler biopsy. However, the inaccuracy of D&C alone necessitates further preoperative and intraoperative assessment for other risk factors to determine the aggressiveness with which an individual patient should be staged surgically.

Experimental evidence is presented that supports a cell cycle model showing that there are five distinct biological processes involved in proadipocyte differentiation. These include: (a) growth arrest at a distinct state in the G1 phase of the cell cycle; (b) nonterminal differentiation; (c) terminal differentiation; (d) loss of the differentiated phenotype; and (e) reinitiation of cell proliferation. Each of these events is shown to be regulated by specific human plasma components or other physiological factors. At two states designated GD and GD', coupling of growth arrest and differentiation is shown to occur. We propose that these mechanisms for the coupling of growth arrest and differentiation are physiologically significant and mimic the regulatory processes that control stem cell proliferation in vivo.

Our preliminary experience indicates that even high-risk patients have an excellent prognosis when treated with surgery, including pelvic and para-aortic lymphadenectomy, without radiotherapy.