Novel molecular profiles of endometrial cancer-new light through old windows.

Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology. Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers. In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium. Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types.

Cord blood lipoprotein-cholesterol: relationship birth weight and gestational age of newborns.

Umbilical plasma levels of lipoproteins-cholesterol were measured in 60 premature (less than 37 weeks), 60 small for gestational age (SGA, greater than 37 weeks), and 60 full term newborns (greater than 37 weeks) to ascertain the relationship between gestational age, infant's weight and concentration of plasma lipoprotein cholesterol. Umbilical levels of total cholesterol (TC), unesterified cholesterol (UC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in premature newborns were significantly higher (P less than .001) than in term infants. The levels of TC, UC, HDL-C and very low density lipoprotein cholesterol (VLDL-C) were substantially higher (P less than .05) in umbilical cord plasma of SGA newborns than in cord plasma of full term newborns. Lecithin:cholesterol acyltransferase activity in cord plasma was indirectly assessed by measuring the ratio of esterified cholesterol to unesterified cholesterol (CE/UC). This ratio was significantly lower (P less than .01) in preterm and SGA than in full term newborns. In addition, plasma TC, UC, LDL-C and HDL-C levels were inversely correlated with gestational age of newborns. By contrast, CE/UC ratio had an inverse correlation with gestational age and HDL-C of the newborns. These findings suggest that the levels of TC in newborns are regulated by the uptake of LDL-C by the fetal adrenal and, additionally, by the lecithin:cholesterol acyltransferase (LCAT) activity of newborn plasma. Only by careful follow-up of hyperlipidemic neonates can the true incidence of familial hyperlipoproteinemia and the value of early diagnosis be assessed.

Plasma lipids and high density lipoprotein cholesterol in maternal and umbilical vessels in twin pregnancies.

Total cholesterol (TC), triglycerides (TG), phospholipids (PL), Unesterified cholesterol (UC) and high-density lipoprotein cholesterol (HDL) were measured in 30 plasmas from twin pregnant women and their newborns, and 60 maternal single infant pairs. Blood samples were obtained simultaneously from maternal vein, umbilical artery and umbilical vein at the moment of partum. TG from twin pregnant mothers was much higher and HDL-C lower than that from single pregnant maternal plasma TC, TG and PL in umbilical cord vessels showed no differences between twin and single newborns. There was a weak, but statistically significant, positive correlation between maternal and fetal levels of PL in both groups. A high difference between TC, TG and PL in umbilical venous and umbilical arterial plasma was found These data suggest that some fetal lipid moieties derived from maternal plasma. But data about fetal body composition indicate that contribution of maternal lipids to the fetus is of small quantitative importance.

Plasma lipids, apolipoproteins A and B in maternal and umbilical vessels in term pregnancies.

Total cholesterol (TC) high density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A (Apo A) and apolipoprotein B (Apo B) were measured in 40 plasmas from term pregnant women at vaginal delivery. Blood samples were obtained simultaneously from the maternal vein, umbilical artery and umbilical vein. The mean values of lipids and apolipoproteins were significantly (P less than 0,0001) lower in umbilical vessels than in the mother. TC, HDL-C, TG and Apo B were significantly (P less than 0,0005) higher in umbilical vein than in umbilical artery. No significant differences in Apo B levels were found between umbilical vein and artery.