Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA-negative breast cancer patients in Greece.

PURPOSE: BRCA mutation carriers can benefit from targeted clinical interventions. On the other hand, families with evident aggregation of breast cancer (BC) cases and a BRCA-negative genetic test can still be considered as of elevated risk, since the underlying genetic factor remains unidentified. In the present study, we compared clinical and demographic characteristics between BRCA1 mutation carriers (BRCA1mut) and non-carriers (non-BRCA1) in a Greek group of BC patients (n=321). METHODS: Data were collected and analyzed from 321 women with BC, with 131 patients screened for pathogenic mutations in the high-penetrant genes BRCA1 and BRCA2. Collected data included demographics, pedigrees, tumor histopathology and immunohistochemistry findings. RESULTS: In BRCA1mut patients, their mothers and grand- mothers were diagnosed at a younger age compared to non-BRCA1-carriers. Additionally, BRCA1mut patients were diagnosed with mainly estrogen receptor (ER) negative (p<0.001), Her-2 negative (p<0.05) and triple negative (p<0.01) tumors. The youngest generation was diagnosed with familial breast cancer (FBC) 9.7 years earlier than their mothers (p<0.001). Age at BC diagnosis negatively correlated with the nuclear grade of breast tumors (r=-0.3, p<0.05). Among parous individuals, the number of full-term pregnancies significantly correlated with the age at BC onset (r=0.19, p<0.05). CONCLUSION: Despite their similarities, FBC cases with identified BRCA1 mutations exhibit a clearly distinct profile. We have identified an anticipation effect in FBC patients, with significantly reduced age at diagnosis in younger generations. Increased parity seems to prevent early BC onset. This is the first study comparing clinical and demographic characteristics of FBC BRCA1mut and non-carriers in a Greek cohort.

Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists.

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH), is distinguished in its classical and nonclassical form and is one of the most common autosomal recessive inherited diseases in humans. The classical form appears between 1:5000 and 1:15000 among the live neonates of North America and Europe, whereas the nonclassical form occurs in approximately 0.2% of the general white populations. Three alleles are associated with the 21-OH locus and can be combined in various ways to individuals who are either unaffected, heterozygote carriers, or affected with the classical or nonclassical disease. Variable signs and symptoms of hyperandrogenism are common to both types of the disorder. In women with CAH, hyperandrogenism may be present, extending from virilization of external genitalia and salt-wasting in classical (C)-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders such as hirsutism, in nonclassical (NC)-CAH cases. These clinical characteristics of NC-CAH cases do not differ unmarkedly from those shown in patients with polycystic ovary syndrome, idiopathic hirsutism, or hyperinsulinemia. The significant advances in molecular biology and gene analysis over the past 2 decades have led to the development of novel sensitive methods of DNA analysis and study, including polymerase chain reaction and Southern blot analysis. Thus it has been revealed that the 21-OH gene (CYP21A2) and its nonfunctional pseudogene (CYP21A1P) are located on chromosome 6 (6p21.3), sharing a high homology of about 98%. Inactivating mutations occur as complete gene deletions, large gene conversions and pseudogene-derived mutations.

The prevalence of non-classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Greek women with hirsutism and polycystic ovary syndrome.

UNLABELLED: The study was aimed to find out the prevalence of non-classical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (21-OHdef) among Greek women with hirsutism and polycystic ovary syndrome (PCOS) and to compare the results of ACTH stimulated 17-hydroxyprogesterone 60 min (17-OHP60) values, with human leukocyte antigens (HLA) phenotypes, in any patient diagnosed as having NC-CAH. One hundred and seven women with hirsutism and PCOS were included in the study. All were presented at the Reproductive Endocrinology Outpatient Clinic with hirsutism and PCOS. After ACTH stimulation test, 10 women were diagnosed as having NC-CAH because of high 17-OHP60 values >or=36 nmol/l, and 97 as having PCOS. Ten (10.3%) of the 97 women presented hormonal findings compatible with adrenal hyper-response due to ACTH testing, because of hyperstimulated 17-OHP60 values >or=21 nmol/l and <32 nmol/l. The HLA typing of 10 patients with NC-CAH revealed the phenotypes B14, DR1, B35, B7 and B44 which present positively genetic linkage disequilibrium with 21-OHdef, as reported in the literature. IN CONCLUSION: In Greek women with hirsutism and PCOS we have found that: a. The prevalence of NC-CAH among these women is relatively high and reaches at 10%. b. The HLA phenotypes B(14), DR(1), B(35), B(7) and B44 were found in high frequency in these NC-CAH patients. c. Adrenal NC-CAH due to 21-OHdef as well as adrenal hyperactivity, revealed after ACTH testing, constitutes an important reason of hirsutism and PCOS in these Greek women and both reach a rate of 20%.

The influence of vacuum extractor on fetal oxygenation and newborn status.

AIM: The aim of this study was to determine the effects of vacuum extractor assisted delivery on fetal oxygenation and acid-base balance. METHODS: Sixty-one women were enrolled in the present study. The subjects were divided into two groups. Group A, consisting of 39 women, had normal vaginal deliveries. Group B, consisting of 22 women, underwent a vacuum extractor assisted vaginal delivery. Fetal arterial oxygen saturation (SpO2) monitoring was used in all women after full cervical dilatation. After delivery, umbilical artery pH, pCO2, pO2 and base deficit (BDecf) levels were determined in all neonates. RESULTS: The mean FSpO2 value in Group A was 51.53+/-5.87% and in Group B 48.03+/-6.39% (p<0.03). The mean cord pH value in fetuses of Group A was 7.26+/-0.05, and in Group B 7.17+/-0.09. There was also a significant difference between the two groups with regards to mean pO2, pCO2 and BDecf values. CONCLUSIONS: Vacuum assisted vaginal delivery was associated with lower fetal arterial oxygen saturation levels as well as lower cord blood pH values compared to those seen after unassisted vaginal delivery. Although decreased, however, the above parameters remained within normal ranges.