The validation of estrogen receptor 1 mRNA expression as a predictor of outcome in patients with metastatic non-small cell lung cancer.

The prognostic role of estrogen receptors in lung cancer is not validated. Results from patients with early stage non-small lung cancer patients indicate a prognostic role of estrogen receptor 1 (ESR1) mRNA expression in these patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of tumoral ESR1 and progesterone receptor (PGR) mRNA expression. The test cohort consisted of 31 patients with advanced or metastatic non-small cell lung cancer (NSCLC) patients, treated in a first-line registry trial. For validation, 53 patients from a randomized multicentre first-line study with eligible tumor samples were evaluated. There was no significant correlation of ESR1 expression with clinical characteristics. ESR1 high expression was of significant positive prognostic value in the training set with a median overall survival (OS) of 15.9 versus 6.2 months for high versus low ESR1 expression patients (p = 0.0498, HR 0.39). This could be confirmed in the validation cohort with a median OS of 10.9 versus 5.0 months in ESR1 high versus low patients, respectively (p = 0.0321, HR 0.51). In the multivariate analysis adjusted for histological subtype, gender, age and performance status, ESR1 expression remained an independent prognostic parameter for survival in both cohorts. In contrast to ESR1, PGR expression was not able to separate prognostic groups or to predict outcome significantly (for OS; p = 0.94). Our study shows that ESR1 mRNA as assessed by qPCR represents a reliable method for detecting ESR1 expression in NSCLC and that ESR1 expression is an independent prognostic factor in metastatic NSCLC.

Prognostic and predictive value of estrogen receptor 1 expression in completely resected non-small cell lung cancer.

Adjuvant chemotherapy (ACT) leads to a modest improvement in survival among patients with completely resected non-small cell lung cancer (NSCLC) but molecular predictors are still rare. Publicly available gene microarray, clinical and follow-up data from two different studies on early-stage NSCLC were used to determine the expression of estrogen receptor 1 (ESR1). Expression values were calculated against clinical and survival data in a training set (n = 138) and a test set (subpopulation from the adjuvant JBR.10 study) allowing the determination of the prognostic effect of ESR1 in the observational arm as well as the predictive effect of ESR1 regarding ACT. Data were well balanced in terms of ESR1 expression. ESR1 high expression was of significant positive prognostic value in the training set and this could be confirmed in the test set cohort (hazard ratio for overall survival 0.248, 95% confidence interval: 0.088-0.701; p = 0.008). Additionally, ESR1 low tumors showed a benefit from ACT in terms of 5-year survival (33.3% observation arm and 77.8% ACT arm; p = 0.003), whereas patients with ESR1 high tumors did not have any benefit from ACT (test of interaction p = 0.024). ESR1 is an independent positive prognostic factor for survival in early-stage NSCLC patients. Patients with ESR1 high tumors did not benefit from ACT.

Resistin levels in patients with obstructive sleep apnoea syndrome--the link to subclinical inflammation?

BACKGROUND: The role of resistin, a "new" white adipose tissue hormone, still needs to be established. Its linkage to insulin sensitivity and body mass was controversial in previous studies. MATERIAL/METHODS: Twenty obese patients (BMI: 32.1+/-6.9 kg/m2 ) with obstructive sleep apnoea syndrome (OSAS) (Apnoea-Hypopnoea Index: 48.6+/-19.1, underwent measurements of resistin, interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), CRP and the insulin sensitivity index (ISI) by hyperinsulinaemic euglycaemic clamp before, 2 days and 2 months after onset of CPAP treatment. RESULTS: Resistin remained unchanged during CPAP-therapy and was negatively correlated to ISI (r=-0.359; p=0.006), the latter was significantly improved by CPAP (p<0.001). In a correlation matrix, IL-6 and ICAM-1 were significantly (p=0.001) correlated to resistin (p=0.614 and 0.427). Changes of inflammatory markers under CPAP treatment were related to AHI, as well as resistin changes. CONCLUSIONS: In agreement with previous investigations, we could only demonstrate a weak linkage between ISI and resistin. However, at least in obese patients with OSAS, there is a close relation to subclinical inflammation (IL-6) and endothelial activation (ICAM-1).

The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes.

BACKGROUND: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. OBJECTIVES: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. METHODS: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 +/- 21.3; body mass index (BMI) 37.3 +/- 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 +/- 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. RESULTS: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 +/- 2.94 vs. 2.74 +/- 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 +/- 0.6%; not significant). Fasting leptin levels showed no significant changes. CONCLUSIONS: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.

Launois-Bensaude syndrome in a female with type 2 diabetes.

BACKGROUND: The Launois-Bensaude syndrome (LBS) is a rare disease characterized by an accumulation of multiple lipomata with a preponderance at the thorax, abdomen, upper arms and the thighs. Frequently, the condition is associated with past or present alcohol abuse with no clear temporal coincidence between the onset and termination of lipomata growth and onset or termination of alcohol consumption. Due to the massive accumulation of adipose tissue, the patients frequently have features of the metabolic syndrome as hypertension, impaired fasting glucose or diabetes mellitus, hyperuricemia or hyperlipidemia. CASE REPORT: A 79-yr-old female observed an increase of fat mass especially at the upper arms, the thighs and the thorax in combination with a weight gain of 19 kg within 2 years without any changes in the nutrition habits. The unique features confirmed the diagnosis of LBS. Interestingly, she had diabetes mellitus, hypertension and hyperlipidemia before the manifestation of LBS and without any history of heavy alcohol consumption. Furthermore, the condition predominantly affects males. In her very case, treatment with sultanol, as successfully performed in some cases, could not be recommended due to her cardiac insufficiency. A surgical approach is of limited value due to the frequent relapses of the lipomata. CONCLUSIONS: Establishing the diagnosis of LBS is an important step for patients confronted with an inexplicable physical disfigurement that is not related to excessive nutrition. The disease is often not diagnosed because of its rareness, but its features are unique and easily to be distinguished from 'simple' truncal obesity.