PTEN as a molecular marker to distinguish metastatic from primary synchronous endometrioid carcinomas of the ovary and uterus.

The distinction between two primary carcinomas on the one hand and a metastatic disease on the other hand in patients suffering from synchronous endometrioid carcinomas of the uterus and ovary is difficult. Exclusive histopathologic analysis appears to be insufficient and sometimes misleading. The tumor suppressor PTEN was found to be important in early neoplastic transformation in endometrioid carcinomas of the uterus. In this study, we screened synchronous endometrioid carcinomas of the uterus and ovary of 10 patients for loss of heterozygosity using seven different microsatellite markers at 10q23.3 and for mutations in the entire coding region of PTEN. Point mutations or microdeletions/insertions were found in six patients. Allelic loss at 10q23.3 was detected in eight patients. Based on conventional histology, a metastatic disease was diagnosed in seven patients and a concomitant uterine and ovarian carcinoma in three patients. After molecular analysis, the histopathologic diagnosis of three patients had to be revised. Histopathology represents the standard method to process tumor specimens from these patients. Nevertheless, mutation screen for PTEN and LOH analysis at 10q23.3 provide helpful genetic tools to establish a correct final diagnosis, which is important in view of prognosis and therapeutic implications.

Endothelial and smooth muscle cell dysfunction in human atherosclerotic radial artery: implications for coronary artery bypass grafting.

The radial artery (RA) is increasingly used as coronary artery bypass graft. In rare cases, however, it is macroscopically atherosclerotic at time of harvest. We examined how the regulation of vascular tone is altered under such circumstances. Macroscopically evident atherosclerotic lesions were observed in 3 of 429 RA (0.7%) isolated within 2 years. Histology revealed severe plaque formation; however, von Willebrand Factor staining showed a morphologically intact endothelium (n = 3). Endothelium-dependent relaxations to acetylcholine (10(-5) M) were reduced in atherosclerotic RA (32 +/- 6%; n = 3) as compared with control (78 +/- 4%; n = 10; P = 0.0001). Receptor-independent contractions to KCl (100 mM) were reduced in atherosclerotic RA (33.19 +/- 5.06 mN; n = 3) as compared with control (108.02 +/- 15.76 mN; n = 9; P < 0.05). Similarly, contractions to thrombin (1 U/ml) were reduced in atherosclerotic RA (3.02 +/- 1.58 mN; n = 3) as compared with control (10.97 +/- 5.12 mN; n = 8). Likewise, receptor-mediated contractions to norepinephrine were reduced in atherosclerotic RA (27.64 +/- 12.48 mN; n = 3) as compared with control (82.74 +/- 11.36 mN; n = 9; P < 0.05). Atherosclerosis is rare in RA of patients with coronary artery disease, but it does occur. Atherosclerotic RA exhibits a dysfunction of both endothelium and vascular smooth muscle. This dysfunction may favor thrombus formation and accelerated atherogenesis. Therefore, atherosclerotic RA should not be used for coronary artery bypass grafting.