Smoking effects on quality of life of allergic rhinitis patients after sublingual immunotherapy.

BACKGROUND: Although tobacco smoking is of great concern, there is no evidence for the effects of smoking on quality of life (QoL) results after sublingual immunotherapy (SLIT). OBJECTIVE: This study aims tο explore any association between smoking habits (duration and quantity) and QoL results after SLIT in allergic rhinitis (AR). METHODOLOGY: One hundred and sixty three patients following SLIT for AR were participated. SLIT efficacy related to smoking was prospectively evaluated by means of validated widely used QoL questionnaires, either for assessing psychology (Zung Anxiety Scale, State-Trait Anxiety Inventory, Zung Depression Scale and Beck Depression Inventory) or generic (Short Form-36) ones, pre- and immediately upon cessation of SLIT. Smoking habits were expressed in pack-years. RESULTS: Significant improvement of total symptoms score (T5SS) and of all QoL questionnaires' results were observed in our patients' group, both for smokers and non smokers. The comparison of changes between smokers and non smokers, controlling for the effect of all patients' characteristics, showed that there was no significant differences on improvement values. Additionally multivariate linear regression analysis revealed that the effect of pack-years on the QoL scales was not significant. CONCLUSIONS: Our results suggest that smoking habits (quantity of daily smoking and duration) do not influence the success of SLIT with regards to QoL outcomes.

Body fat distribution by anthropometric and MRI-based techniques in relation to insulin secretion and action in men with diabetes.

AIM: Differences in fat accumulation and distribution might be responsible for the greater insulin resistance (IR) in type 2 diabetes. The study aims at examining the relationship between fat accumulation and distribution, and insulin secretion and action, by multilevel methodological approach. METHODS: Thirty-three diabetic men (D), and 28 sex, age and BMI-matched controls (C) were studied for glucose and insulin during OGTT, insulin resistance and sensitivity, employing HOMA and Matsuda index respectively, and, fat accumulation and distribution by anthropometrics, Bioimpendance Analysis (BIA), and multiple slices MRI of abdomen and hip. RESULTS: D exhibited higher HOMA compared to C (P<0.001), and lower Matsuda index (P=0.062). No differences in fat distribution by anthropometric or MRI measurements were observed; however, fat accumulation by BIA was higher in D (P=0.035). HOMA correlated to basal, AUC, and peak insulin in both groups (all P<0.001); with weight (r=0.415, P=0.031), hip circumference (HC) (r=0.482, P=0.011), %fat (r=0.400, P<0.05) in C; and with weight, BMI, total and %fat, and waist and HC when all subjects were considered as a group. Matsuda inversely correlated with basal, AUC, and peak insulin (all P<0.001), and HC (r=-0.406, P=0.032) in C. HOMA strongest correlated with L3-L4 subcutaneous (r=0.551, P=0.003) in C, and with L3-L4 visceral (r=0.456, P=0.022) in D. CONCLUSION: The greater IR in diabetic patients may not be interpreted by differences in fat distribution. IR correlates with different fat compartments in healthy and diabetic subjects of comparable fat distribution, suggesting differences in fat function.

Coexpression of IL-6 and TNF-α: prognostic significance on breast cancer outcome.

Presented study was conducted to investigate the prognostic significance of the coexpression of serum interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in breast cancer, by correlating their presence with clinicopathological characteristics indicative of tumor progression and the overall survival of breast cancer patients. One hundred twelve consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of IL-6 and TNF-a were measured by quantitative sandwich enzyme immunoassay (ELISA). Median split was used to subdivide patients with low or high IL-6 and TNF-a levels. A positive association between the expression of the two cytokines was found. The coexpression of high IL-6 and TNF-α was independently associated with extended lymph node (>3) involvement (aOR, 7.8) and lymphovascular invasion (aOR, 14.1), increasing the prognostic significance of each cytokine separately; it also provided additional prognostic information regarding survival, defining a high-risk subgroup of patients with significantly shorter survival and higher risk of death compared to patients with both cytokines low (aHR, 4.45) and patients with only one cytokine high (aHR, 3.63). Our findings suggest that the coexpression of these two cytokines could be used clinically as a useful tumor marker for the extension and the outcome of the disease.

B7H4, HSP27 and DJ-1 molecular markers as prognostic factors in pancreatic cancer.

OBJECTIVES: Pancreatic cancer (PC) is one of the most lethal tumors of the gastrointestinal tract. The ability to predict which patients would benefit most from surgical intervention and chemotherapy would be a great clinical tool. A large number of potential markers have been identified lately in pancreatic cancer and their clinical utilities as prognostic tools are under investigation. METHODS: We recruited 41 patients who had undergone radical surgical resection for PC between 2003 and 2010. To investigate the prognostic factors, we evaluated 3 possible markers: B7H4, HSP27 and DJ-1 protein expressions in the tissue specimens of these 41 patients by immunohistochemistry and analyzed the clinical and pathological features of these specimens. RESULTS: The expression of the three antigens was independently associated with a negative impact of chemotherapy with gemcitabine on patient's survival. Moreover, patients who overexpressed B7H4 had worse prognosis than the ones who did not. CONCLUSIONS: B7H4, DJ-1 and HSP27 may be used in the future as prognostic markers that express resistance of pancreatic cancer patients to chemotherapy with gemcitabine.

Silicone ring tourniquet versus pneumatic cuff tourniquet in carpal tunnel release: a randomized comparative study.

BACKGROUND: The aim of the present study was to compare the pain levels resulting from the use of a silicone ring tourniquet (SRT) to those resulting from the use of a classic pneumatic cuff tourniquet (PT) in patients undergoing carpal tunnel release under local anesthesia. MATERIALS AND METHODS: Fifty patients that underwent carpal tunnel release under local anesthesia were randomized using the technique of stratified randomization by minimization. A forearm tourniquet was applied: a standard PT was used in 25 patients, and an SRT was used in the other 25 patients (the model of SRT used was selected according to the standard systolic blood pressure). Patient demographics and complications were recorded. Pain levels were assessed with the visual analogue scale and were recorded (a) just after tourniquet application, (b) 5 min after tourniquet application, and (c) just before tourniquet removal. RESULTS: There was no statistical significant difference in patient demographics between the two groups. The mean tourniquet time was similar for both groups (p = 1.000). The difference between the mean final pain level and the mean initial pain level was statistically significant for the SRT group (p = 0.010) and highly statistically significant for the PT group (p < 0.001). The mean final pain level for the PT group was higher than that for the SRT group (p = 0.043). CONCLUSIONS: According to the findings of this study, in patients who underwent carpal tunnel release under local anesthesia, the pain levels at the end of the operation and those just before the removal of the tourniquet were higher in the PT group than in the SRT group of patients.

Sociodemographic and clinical characteristics of Roma and non-Roma psychiatric outpatients in Greece.

OBJECTIVE: Differences in psychiatric symptoms are often reported between minority and majority groups. The aim of this study was to compare Roma psychiatric outpatients who are Greek citizens living in Thrace (Greece) with outpatients belonging to the 'majority Greek group' with respect to socio-demographic characteristics, psychopathological symptoms and psychiatric diagnoses. DESIGN: A sample of 122 Roma and 132 majority Greek patients visiting the Outpatient Psychiatric Clinic at the University General Hospital of Alexandroupolis, Greece, were examined with the Structured Clinical Interview for DSM III-R (SCID-I), the International Personality Disorder Examination (IPDE) and the Derogatis Psychiatric Rating Scale (DPRS). Only those with a psychiatric diagnosis were retained in the analyses. The two groups of patients were compared in relation to their socio-demographic characteristics, their diagnoses and their scores on the DPRS symptom dimensions. RESULTS: In comparison to the majority group, Roma patients were younger, more often women, less educated, married, parents of more children, without social security coverage; The Roma group had higher scores on many DPRS symptom dimensions such as somatisation, hostility, sleep disturbance, phobic anxiety, psychoticism, psychomotor retardation, hysterical behaviour and abjection-disinterest. In addition, Roma women presented psychotic and bipolar disorders less often than the majority group women. Symptoms did not differ by ethnic group for those seeking medical certification. CONCLUSION: Roma patients face serious social problems and show greater levels of symptoms than the majority group. The limitations of this include that the sample was not representative of the general psychiatric patient population and language, as well as other cultural and educational barriers, might have obscured important aspects of the Roma people's psychopathology.

Laparoscopic cholecystectomy in acute cholecystitis: an analysis of the risk factors.

BACKGROUND AND AIM: Laparoscopic cholecystectomy (LC) is increasingly being used as the initial surgical approach in patients with acute cholecystitis (AC). We describe our experience with LC in the treatment of AC. MATERIALS AND METHODS: In this study 2 412 patients underwent LC, in 315 cases for AC. The diagnosis was based on clinical, laboratory and intra-operative findings. Rates of conversion, complications, length of hospital stay, operating times, and factors associated with conversion or morbidity were analysed. RESULTS: Conversion to open cholecystectomy was necessary in 60 patients (19.04%) with AC. Factors associated with conversion were age >65 years, male gender, presence of empyema, previous abdominal surgery, and fever (temperature >37.5oC). There were no deaths, and the complication rate was 6.4%. The only risk factor for morbidity was a bilirubin level of >20.52 µmol/l. The operating time and hospital stay were significantly longer in AC than in elective cases. CONCLUSIONS: LC for AC is technically demanding but safe and effective. With patience, experience, careful dissection and identification of vital structures, the laparoscopic approach is safe in the majority of cases.

The Rhinoconjunctivitis Quality of Life Questionnaire and its modified short version validation in adults and children with allergic rhinitis.

OBJECTIVE: This study aimed to develop the Greek versions of the Rhinoconjunctivitis Quality of Life Questionnaire and Mini-Rhinoconjunctivitis Quality of Life Questionnaire for adult and pediatric populations, discuss their differences and detect the impact of age and gender on quality of life questionnaire results. METHOD: Ninety-eight patients with allergic rhinitis participated. Quality of Life evaluation was made by two generic (Short Form-36 and Beck Depression Inventory) and two disease-specific questionnaires (Rhinoconjunctivitis Quality of Life Questionnaire and Mini-Rhinoconjunctivitis Quality of Life Questionnaire). Symptom evaluation was made by the Total 5 Symptoms Score assessment. RESULTS: Internal consistency and test-retest reliability of both questionnaires was high. Convergent validity showed statistically significant negative correlations of total Rhinoconjunctivitis Quality of Life Questionnaire and Mini-Rhinoconjunctivitis Quality of Life Questionnaire with overall Short Form-36 Health Survey score and positive correlations with Beck Depression Inventory and Total 5 Symptoms Score. Discriminative validity demonstrated statistically significant improvement for all instruments and all domains after treatment. Females presented highly significant increased scores. Patient age was positively correlated with total scores of Rhinoconjunctivitis Quality of Life Questionnaire and Mini-Rhinoconjunctivitis Quality of Life Questionnaire. The clinically significant improvement after treatment was higher among females than males, while it was independent of patient age. CONCLUSION: Rhinoconjunctivitis Quality of Life Questionnaire and Mini-Rhinoconjunctivitis Quality of Life Questionnaire proved to be valid and reliable methods of assessment of allergic rhinitis-related quality of life in children, adolescents and adults.

Oculomotor nerve palsy due to posterior communicating artery aneurysm: Clipping vs coiling.

OBJECTIVE: Posterior communicating artery aneurysms (PCoAA) usually present with brain hemorrhage, but they might present with oculomotor nerve palsy (ONP) in about one out of five patients. Treatment options include endovascular coiling and surgical clipping. The present analysis aims to compare the two treatment options for ONP due to PCoAA in terms of complete recovery and related parameters. METHODS: A comprehensive literature search was performed for studies published between 2000 and 2019 on ONP due to PCoAA. The included studies were divided into two categories-surgical clipping (group A) and endovascular coiling (group B). The collected data were statistically processed with SPSS version 25. RESULTS: There was a significant difference between the two treatment groups regarding complete recovery of ONP (P<0.001), suggesting superiority of the surgical clipping. The correlation analysis showed no correlations for group A. Group B had negative and positive correlations, showing that endovascular coiling results in higher rates of complete ONP recovery for elderly patients. CONCLUSION: Surgical clipping is superior to endovascular coiling in terms of complete recovery among patients with ONP due to PCoAAs. Endovascular coiling seems to benefit older patients. While no recommendations exist for the treatment of ONP due to intracranial aneurysms, an increasing number of studies imply the superiority of operative clipping.

Increased seroprevalence of Toxoplasma gondii in a population of patients with Bell's palsy: a sceptical interpretation of the results regarding the pathogenesis of facial nerve palsy.

Facial nerve oedema and anatomical predisposition to compression within the fallopian tube seem to be the only generally accepted facts in the pathophysiology of Bell's palsy. Several infectious causes have been suggested as possible triggers of this oedema. Most of the suggested pathogens have been associated with facial nerve lesions during latent infections, reinfections or endogenous reactivations. The aim of this study was to investigate the seroprevalence of three such pathogens Toxoplasma gondii, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in a population of patients with facial nerve palsy. Fifty-six patients with Bell's palsy were included in the study. A group of 25 individuals with similar age and gender distribution was used as control. Seropositivity for T. gondii, EBV viral capsid antigen (VCA) and CMV-specific IgM and IgG antibodies was investigated 2-5 days after the onset of the palsy. Comparisons for both IgM and IgG antibodies against T. gondii attributed significantly higher seroprevalence in the patients' group than in the control group (p = 0.024 and 0.013, respectively). The respective examinations for EBV and CMV attributed no significant results. The roles of EBV and CMV in the pathogenesis of Bell's palsy were not confirmed by this study. However, a significantly higher seroprevalence of IgM- and IgG-specific T. gondii antibodies was detected in patients with Bell's palsy when compared to healthy controls. The possibility that facial nerve palsy might be a late complication of acquired toxoplasmosis may need to be addressed in further studies.

Serum pattern of circulating soluble receptor of leptin throughout the menstrual cycle.

AIM: The aim of the study was to investigate the pattern of circulating soluble receptor of leptin (sLeptinR) during the menstrual cycle and the association of sLeptinR to leptin, sex hormones and gonadotropins. METHODS: Fasting blood samples were collected on alternate days throughout a full cycle from fifteen healthy volunteers. Immunoenzymatic assays were employed to record the relevant levels. RESULTS: sLeptinR concentrations throughout the cycle were found to vary negligibly. No significant correlations between sLeptinR and leptin, gonadotropins or progesterone, were established. During the follicular phase, subjects presenting with higher estradiol levels tended to have higher sLeptinR concentrations. CONCLUSION: The little variation of sLeptinR concentrations during the menstrual cycle indicates that the rise of leptin during the luteal phase implies an increase of its bioactivity.

Reliability and validity of the Diabetes Eating Problem Survey in Greek adults with type 1 diabetes mellitus.

Ιn the management of type 1 diabetes mellitus (T1DM), dietary therapy and the maintenance of a healthyΙn the management of type 1 diabetes mellitus (T1DM), dietary therapy and the maintenance of a healthy body weight (in conjunction with insulin therapy) are significantly associated with good glycemic control and complication reduction. However, a diabetic patient's increased focus on diet and weight control,although necessary, can lead to disturbed eating habits, medical complications, and "resistance" to treatment. The term "diabulimia" refers to the eating disorder in which patients with T1DM take less insulinin order to control their weight. Currently there is no valid questionnaire in the Greek language for the detection of eating disorders in T1DM. This study examines the psychometric properties of the Greek version of the Diabetes Eating Problem Survey-Revised (DEPS-R), a questionnaire that assesses the risk of "diabulimia"in patients with T1DM. 100 outpatients with a T1DM diagnosis of over one year -71 women and 35users of a continuous insulin infusion pump- were asked to complete the DEPS-R questionnaire translated into Greek (0-80 score range, >20 indicating high risk of disorders) along with the EAT-26 (0-78 score range,>20 indicating high risk of pathological eating behaviours or eating disorder) and the Beck Depression Inventory (BDI-ΙΙ) (0-63 score range, >14 indicating high risk of major depressive disorder). The Greek versionof the DEPS-R showed strong internal consistency and construct validity (Cronbach's alpha=0,89 in total,0,90 in females and 0,85 in males). Factorial analysis revealed 4 factors (diet, weight loss, insulin use and compensatory behaviors) accounting for 65.68% of the total variance (19.90%, 18.50%, 15.64% and 11.65%of the total variance respectively). In addition, 35% of the sample scored above 20 on the EAT-26, 26% rated above 14 on the BDI-II and 40% had a score above 20 on the DEPS-R, while the average score was 19.22. The sound psychometric properties of the DEPS-R scale were confirmed for a Greek sample with T1DM suggesting that it could be used as a reliable tool for the detection of diabulimia. In addition, we found that Greek patients with T1DM appear to have an increased risk of developing eating disorders and depression.

Vitamin D in mild cognitive impairment and Alzheimer's disease. A study in older Greek adults.

BACKGROUND: In recent years, accumulating evidence has linked vitamin D deficiency to cognitive dysfunction and dementia. This study aimed at determining the relevance of serum 25-hydroxyvitamin D concentrations in mild cognitive impairment (MCI) and Alzheimer's disease (AD) in older Greek adults. It also examined whether the vitamin D level could be considered a predisposing factor for conversion from MCI to AD. METHODS: The study enrolled 350 subjects aged 65 years and over, allocated into three groups consisting of 103 healthy subjects (HS), 109 individuals with MCI, and 138 patients with AD, respectively. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, measured in ng/ml, were determined by electrochemiluminescence, and we used the Mini-Mental State Examination (MMSE) and the Cambridge Cognition Examination (CAMGOG) to evaluate the subjects' cognitive status. One follow-up examination was performed for the MCI patients 30 months ± three months after the initial evaluation. RESULTS: Compared to HS, serum 25(OH)D levels were significantly decreased in individuals with MCI (p =0.012) and patients with AD (p <0.001). Moreover, serum 25(OH)D concentrations were significantly decreased in patients with AD compared to individuals with MCI (p =0.003) and also significantly lower in individuals with MCI who progressed to AD compared to those who remained MCI (p =0.028). After adjusting for confounders, multivariate analysis revealed that an increase of vitamin D concentration by one ng/mL reduces the risk of MCI by 4 % (OR =0.96, 95 % CI =0.92-0.99, p =0.006), the risk of AD by 8 % (OR =0.92, 95 % CI =0.89-0.95, p <0.001), and in an individual with MCI reduces the risk of conversion to AD by 10 % (OR =0.90, 95 % CI =0.83-0.96, p =0.003). CONCLUSIONS: The present study reveals that serum vitamin D levels are significantly decreased in subjects with MCI and patients with AD compared to HS. Additionally, individuals with MCI who progressed to AD presented significantly lower vitamin D levels than those who remained MCI. These results suggest that preserving adequate vitamin D status in older adults could delay or prevent cognitive decline. HIPPOKRATIA 2020, 24(3): 120-126.

Theatrical performance in medical education: A fast-track differential approach of emergency cases.

INTRODUCTION: The idea of implementing theatrical acts in medical education has recently been gaining attention, with the inclusion of art-based programs in medical curricula being a growing trend. This study aimed to present an innovative pilot program of presenting medical emergencies through theatrical presentation. MATERIALS AND METHODS: Students-members of the theatrical team of Democritus University of Thrace and the Scientific Society of Hellenic Medical Students were appointed into eight groups, supervised by a clinical tutor. The groups were given four weeks to prepare scenarios for eight different medical emergencies and organize a theatrical sketch accordingly. A 25-item questionnaire was formed and distributed to the audience. Each theatrical act lasted 10 min, followed by a 10 min discussion between the tutors and the audience. After the event, the impressions of the attendees were documented in the questionnaire as responses on a Likert scale from one (strongly disagree) to five (strongly agree). RESULTS: Two hundred and thirty-two fully completed questionnaires were returned. The contribution of theatrical presentation to medical education was widely acknowledged (Likert score 4.14 ± 0.68). Theatrical seminars were not deemed insufficient to provide medical information (disagreed or strongly disagreed 53.8 % and 12.1 %, respectively). Most students were optimistic about the long-term maintenance of the theatrical-aided knowledge, with the majority of attendees (52.1 %) adapting a more favorable response after the seminar (p <0.001). The students' efficacy to recognize medical emergencies was improved (from 2.96 to 3.43, p <0.001). CONCLUSION: Students find the theatrical approach of emergency cases entertaining and educational, facilitating teaching in medicine and enhancing their efficacy to recognize medical emergencies and the commonest pitfalls in their diagnosis and management. Such events may be established as a supplementary educational tools to the classical amphitheatric didactic lectures. Future studies with specific objective tools are needed to validate the abovementioned tasks. HIPPOKRATIA 2020, 24(3): 127-132.

Polymorphisms of the vitamin D receptor gene and stress fractures.

Our aim was to evaluate the association between VDR polymorphisms and calcaneal Stiffness Index (SI) with stress fractures in a case control study including male military personnel. Thirty- two patients with stress fractures were matched with 32 uninjured healthy volunteers (controls), by gender, age, height, body weight, and level of physical activity. The two groups were genotyped for the FokI, BsmI, ApaI, and TaqI polymorphisms of the VDR gene with PCR-RFLP method. In addition, calcaneal SI was measured by heel quantitative ultrasound in both groups. Data were analyzed by chi-squared test and logistic regression analysis. The f allele was significantly more frequent in patients than in controls (p=0.013), while the B allele showed such a tendency without reaching statistical significance (p=0.052). Among the entire cohort, a 2.7-fold and a 2.0-fold increase in risk of stress fractures was associated with the f and B alleles (OR, 2.7, 95% CI, 1.2-5.9; p=0.014 and OR, 2.0, 95% CI, 1.0-4.1; p=0.053, respectively). No statistically significant association was found between the incidence of stress fractures and t or a alleles. Decreased T-scores were also associated with the presence of f and B alleles. Mean values of T-scores of SI were statistically significantly lower in patients than in controls (p=0.018). These results suggest that the FokI and BsmI polymorphisms of the VDR gene could be associated with increased risk of stress fractures among military personnel. Moreover, a low calcaneal SI could represent a measurable index of this increased risk.

Impact of dopamine transporter single photon emission computed tomography imaging using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes.

To assess the impact of I-123 ioflupane single photon emission computed tomography (SPECT) imaging on classifying patients with striatal dopaminergic deficits. Sixty-one patients with an initial diagnosis of parkinsonism or uncertain tremor disorder were screened and followed-up for one year. All patients were re-examined by two neurologists at our centre and were classified as having neurodegenerative or non-neurodegenerative disorders. Patients underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and classified as normal or abnormal (indicative of neurodegenerative disorders). The overall agreement of the SPECT imaging results with the initial classification was 65.6% (kappa=0.229, p=0.074) but was 90.2% (kappa=0.782, p<0.001) with the classification of the neurologists at our centre. I-123 ioflupane SPECT imaging is a valuable method in the evaluation of patients presenting clinically with uncertain parkinsonian syndromes or for whom diagnostic doubt exists.

Long-term bone marrow cultures (LTBMC) from essential thrombocythemia (ET) patients with or without JAK2617V>F mutation.

Approximately half of essential thrombocythemia (ET) patients and almost all with polycythemia vera (PV) bear the activating JAK2617V>F point mutation, which arises at the multipotent haemopoietic progenitor cell level. Although ET is mainly characterized by megacaryocyte proliferation, the cases that are positive for the JAK2617V>F mutation also show increased bone marrow cellularity and higher erythrocyte and granulocyte counts. After establishing short- and long-term bone marrow cultures we found that the frequency of committed haemopoietic progenitors in the bone marrow, was not increased in JAK2617V>F positive ET compared to the negative ones, whereas in long-term cultures (LTBMC) JAK2617V>F positive ET display a growth pattern more similar to that observed in LTBMC produced by PV marrow cells. Our data support the notion that JAK2617V>F positive ET and PV represents a continuum spectrum of alterations within the same disease.

The influence of serum HER-2 levels and HER-2 codon 655 polymorphism on breast cancer outcome.

HER-2 (human epidermal growth factor receptor-2) proto-oncogene is a member of the EGFR family and plays an important role in the regulation of cell growth, differentiation and survival and is involved in the regulation of normal breast growth and development. Alterations of HER-2 have been associated with carcinogenesis and poor prognosis of breast cancer. The present case-control study was conducted to clarify the predictive and prognostic significance of serum HER-2 protein in breast cancer patients in relation to Ile655Val single nucleotide polymorphism (SNP) of this gene. Fifty-six consecutive patients with primary breast cancer and 45 healthy women were prospectively included and evaluated. Serum levels of HER-2 were significantly increased in breast cancer patients compared to healthy controls (p=0.035). The optimal cut-off point of 1.98 ng/ml, which was determined to classify breast cancer patients, yielded sensitivity of 54%, specificity of 73% and accuracy of 62%. Significantly elevated serum HER-2 levels were associated with lymphovascular invasion (p=0.022), poor differentiation (p=0.011), advanced clinical stages (p=0.001), lymph node metastasis (p=0.011), higher number of positive lymph nodes (p=0.007) and the immunohistochemical overexpression of HER-2 protein (p=0.016). Regarding to HER-2 Ile655Val SNP, Ile-Val and Val-Val genotypes exhibited highly significant serum HER-2 elevation compared to homozygous Ile-Ile (both p<0.001). In multivariate analysis advanced stages (p=0.003) and Val-containing genotypes (p=0.009) remained the two significant independent determinants of high HER-2 levels. Survival analysis demonstrated an independent prognostic significance of homozygous Val-Val genotype for reduced survival (p=0.045), but not of serum HER-2 (p=0.181). Our findings confirm that serum HER-2 could be used clinically as a useful tumor marker for the diagnosis and the progression of breast cancer. Furthermore, they provide clinical evidence that HER-2 Ile655Val SNP does affect serum HER-2 levels and it can be regarded as a predictive biomarker for breast cancer patients with poor prognosis.

Evaluation of predictive and prognostic significance of serum TGF-beta1 levels in breast cancer according to HER-2 codon 655 polymorphism.

The present study was conducted to clarify the predictive and prognostic significance of serum TGF-I(2)1 in breast cancer in relation to Ile655Val single nucleotide polymorphism (SNP) of human epidermal growth factor receptor-2 (HER-2). In a case-control study, 56 consecutive patients with primary breast cancer were prospectively included and evaluated. The control group consisted of 45 healthy women. Serum concentrations of TGF-I(2)1 were measured by quantitative sandwich enzyme immunoassay (ELISA). HER-2 SNP was genotyped using PCR-RFLP method. Serum levels of TGF-I(2)1 were significantly increased in breast cancer patients compared to healthy controls (p<0.001). For the evaluation of the diagnostic significance of serum TGF-I(2)1 the area under the receiver operating characteristic (ROC) curve (AUC) was 0.804, while the optimal cut-off point of 30.86 ng/ml was determined to classify breast cancer patients, which yielded sensitivity of 77%, specificity of 78% and accuracy of 77%. Significantly elevated serum TGF-I(2)1 levels were associated with advanced stages (p=0.023), positive lymph nodes (p=0.019) and postmenopausal status (p=0.031). A marginal trend towards higher TGF-I(2)1 levels was found among patients with Val-containing genotypes compared to homozygous Ile-Ile (p=0.094). In multivariate analysis lymph node metastases (p=0.009) remained the only significant independent determinant of high TGF-I(2)1 levels. With regard to prognostic significance for advanced stages (AUC, 0.704) and lymph node metastasis (AUC, 0.683), when the optimal cut-off value was set at 65.15 pg/ml, the sensitivity was 86% and 67%, the specificity was 60% and 62% and accuracy was 66% and 64%, respectively. Survival was shorter in patients with increased serum TGF-I(2)1 (36 months vs 46 months, p=0.022). Multivariate analysis demonstrated a marginal prognostic significance of serum TGF-I(2)1 for survival (p=0.072). The combination of high TGF-I(2)1 and Val-Val genotype predicts a worse prognosis than high serum TGF-I(2)1 alone. Our findings suggest that serum TGF-I(2)1 is involved in tumor malignancy and lymph node metastasis and could be used clinically as a useful tumor marker for evaluation, the extension and the outcome of the disease. They also provide clinical evidence for a significant association between HER-2 Ile655Val SNP and serum TGF-I(2)1, resulting to more aggressive phenotype of the tumor and poor prognosis.

Allelic imbalance of HER-2 codon 655 polymorphism among different religious/ethnic populations of northern Greece and its association with the development and the malignant phenotype of breast cancer.

Alterations of c-erbB-2 (neu or HER-2) proto-oncogene have been associated with carcinogenesis and poor prognosis of breast cancer. A single nucleotide polymorphism (SNP) at codon 655 resulting in a G to A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer. This study aims to determine the prevalence of the HER-2 genotype and its association with breast cancer in the Greek Christian and Greek Muslim population of Thrace, Greece. In this case-control study, we genotyped 56 patients (43 Christians and 13 Muslims) with primary breast cancer and 45 healthy women (32 Christians and 13 Muslims) for the Ile655Val polymorphism, with the PCR-RFLP method. The Val allele and the Val-containing genotypes were significantly more frequent in Muslims than in Christians (p=0.020 and p=0.008, respectively). Among the Greek Christian population, a 5-fold and a 3.1-fold increase in risk of breast cancer was associated with the Val-Val genotype and the Ile-Val or Val-Val genotypes (95% CI, 1.3-18.4; p=0.017 and aOR, 3.1; 95% CI, 1.2-8.3; p=0.025; respectively) compared to homozygous Ile-Ile. No significant association was found in the Muslim population. Among the entire cohort, the Val allele confers a modest increase in breast cancer risk (OR, 2.6; 95% CI, 0.9-7.6; p=0.076, for Val-Val and OR, 2.2; 95% CI, 0.9-5.2; p=0.079 for Ile-Val or Val-Val). This effect was even more pronounced in younger women. Among breast cancer patients, invasive carcinomas, low differentiation tumors, advanced stages, positive lymph nodes, high number of lymph nodes and HER-2 overexpression were more frequent in patients with allele Val than those with allele Ile. Our study proposes the allelic imbalance of Ile655Val polymorphism between Greek Christian and Greek Muslim populations of Thrace contributes to the inconsistent association between this SNP and breast cancer risk across these two different ethnic groups. The association of the HER-2 genotype with clinicopathologic characteristics and HER-2 expression may indicate its possible implication on the more aggressive phenotype.