Mutations of EGFR or KRAS and expression of chemotherapy-related genes based on small biopsy samples in stage IIIB and IV inoperable non-small cell lung cancer

Purposes

Epidermal growth factor receptor (EGFR) and KRAS mutations may predict the outcome of targeted drug therapy and also may be associated with the efficacy of chemotherapy in patients with non-small cell lung cancer (NSCLC). This report investigated the relation of EGFR or KRAS mutation and expression of chemotherapy-related genes, including excision repair cross-complementing 1 (ERCC1), thymidylate synthetase (TYMS), ribonucleotide reductase subunit M1 (RRM1) and class III β-tubulin (TUBB3), as a potential explanation for these observations.

Methods

A total of 143 patients with stage IIIB and IV NSCLC from bronchoscopy or percutaneous lung biopsy obtained tumor samples were analyzed concurrently for EGFR or KRAS mutations, and mRNA expression of ERCC1, TYMS, RRM1 and TUBB3. EGFR or KRAS mutations were detected with xTAG liquidchip technology (xTAG-LCT), and mRNA expression levels of four genes were detected by branched DNA-liquidchip technology (bDNA-LCT).

Results

Of 143 patients, 63 tumors were positive for EGFR-activating mutations, and 16 tumors were positive for KRAS mutations. EGFR-activating mutations are more frequent in females, adenocarcinoma and non-smokers patients, and KRAS mutations are more frequent in smoking patients. ERCC1 mRNA levels were significantly associated with histological type and tumor differentiation, whereas TYMS levels were significantly associated with age. NSCLC specimens that harboring EGFR-activating mutations are more likely to express low ERCC1 and high TUBB3 mRNA levels, whereas tumors from patients with NSCLC harboring KRAS mutation are more likely to express high ERCC1 mRNA levels.

Conclusions

Mutations and expression of chemotherapy-related genes may provide a basis for the selection of suitable molecular markers for individual treatment in a population with stage IIIB and IV NSCLC.     

Tamoxifen as a therapeutic agent in acromegaly

Objective

Administration of high doses of estrogens to patients with acromegaly has been shown to improve symptomatology of acromegaly and glucose tolerance more than 50 years ago. Selective estrogen receptor modulators (SERMs) mimic the effects of estrogen in bone, liver and the cardiovascular system, but function as an anti-estrogen in endometrial and breast tissue. In this study, we evaluated hormonal effects of a SERM, tamoxifen, in active acromegalic patients with particular emphasis on its use in males.

Design

We studied 15 men and 2 post-menopausal women with biochemically-active acromegaly despite the fact that other modalities were ineffective in normalizing their insulin-like growth factor-1 (IGF-1) levels. All patients were treated with tamoxifen 20–40 mg daily for 2–11 months (median of 4 months).

Methods

IGF-1 and growth hormone (GH) levels were assessed immediately before the beginning of treatment and at 2–4 monthly intervals thereafter. Baseline and treatment levels of total and bioavailable testosterone were measured in men.

Results

Tamoxifen did not affect basal GH secretion, but it decreased circulating IGF-I in 14 patients (82 %) by an average of 90 ± 4 mcg/L, (p = 0.005), and normalized plasma IGF-I in 8 patients (47 %). Total and bioavailable testosterone levels increased in all evaluable men (n = 8). Tamoxifen was well tolerated.

Conclusion

Tamoxifen might be useful in the treatment of patients with biochemically-mild active acromegaly, but longer term studies are warranted.     

Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression

Purpose

This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression.

Methods

Gastric cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric cancer progression.

Results

GC-MSC conditioned medium promoted gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric cancer cells in vitro and in vivo.

Conclusions

PDGF-DD secreted by GC-MSCs is capable of promoting gastric cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric cancer cells may represent a novel strategy for gastric cancer therapy.     

Quantitative and immunocytochemical studies of APUD cells in airways and gut

The amine precursor uptake and decarboxylase (APUD) cells in airways and small intestine of adult hamsters have been studied by quantitative, histochemical and immunocytochemical methods for the presence of argyrophilia, ACTH, hGH, calcitonin, bombesin and prolactin in control animals and following priming with two amine precursors: L-dopa and 5-hydroxytryptophane (5-HTP). APUD cells have been defined by the presence of intracytoplasmic argyrophilic granules. A method that related them to airway or gut perimeter length or total epithelial cell numbers has been applied. Calcitonin-like-immunoreactivity (CLIR) is present in epithelial cells in the tracheal epithelium and glands. The presence of ACTH, hGH, bombesin or prolactin is not detected. Priming with L-Dopa and 5-HTP results in up to 12 fold increases in densities of argyrophilic APUD cells in airways and ileum when ratios of APUD cells/100 nuclei are compared to those in control animals. Exposure to 5-HTP induces no significant changes in densities of cells with CLIR in the trachea but CLIR is not detected in animals exposed to L-DOPA. Ratios of APUD cells/100 epithelial cells appear to be more sensitive than those of APUD cells/mm in detecting significant changes in APUD cell densities. Priming with amine precursors is a valuable tool in quantitative studies of neuroendocrine cells.     

Primary pulmonary histiocytosis X immunological analysis in two cases

Several immunological markers were studied in two patients with primary pulmonary histiocytosis X diagnosed by open-lung biopsy. The population of T- and B-lymphocytes from peripheral blood and the response of peripheral lymphocytes to phytohemagglutinin were within the normal ranges in two patients. The concentrations of serum IgG, IgA, and IgM in two patients were normal. However, Patient 1 showed a decreased serum IgE level and Patient 2 showed a lower border-line level of serum IgE as well. The selective low serum IgE level was the only immunological abnormality seen in primary pulmonary histiocytosis X.     

Suppression of Placental Metallothionein 1 and Zinc Transporter 1 mRNA Expressions Contributes to Fetal Heart Malformations Caused by Maternal Zinc Deficiency

Zinc has been implicated to have a protective role against heart malformations during fetal development. Metallothionein 1 (MT-1) and zinc transporter 1 (ZnT-1) are two major metabolic factors that are associated with zinc metabolism. The present work aimed to investigate the association of placental MT-1 and ZnT-1 expressions with fetal heart malformations resulting from maternal zinc deficiency. Sprague–Dawley female rats were randomly divided into five groups of extremely low-zinc, low-zinc, moderately low-zinc, marginally low-zinc and normal zinc (n = 9–12), and were fed diets with controlled zinc content at 1.0 ± 0.3, 8.4 ± 1.8, 15.4 ± 2.8, 22.4 ± 4.1 and 29.4 ± 5.3 [mean ± standard deviation (SD)] mg of zinc/kg, respectively, from day 25 of preconception until day 19 of gestation. The female rats were bred, their fetuses were harvested at day 19 of gestation after killing the dams, and fetal hearts were morphologically examined. Zinc concentration and alkaline phosphatase (ALP) activity in maternal venous blood sera were tested, and MT-1 and ZnT-1 mRNA expressions in the placenta were assayed. Zinc concentrations and ALP activities in the blood were low in all zinc-deficient diet groups in a dose-dependent fashion. The incidences of heart malformations were increased, and the levels of placental MT-1 and ZnT-1 mRNA expressions were decreased in the extremely low-zinc, low-zinc and moderately low-zinc groups compared with the normal zinc group. Specifically, mRNA levels of placental MT-1 or ZnT-1 were significantly decreased and were lower than the specific threshold values in the fetuses with heart malformations but not in the fetuses without heart malformations in all the groups. These data indicate that maternal zinc deficiency resulted in an elevated incidence of fetal heart malformations, which was associated with significant decreases in placental MT-1 and ZnT-1 mRNA expressions to the levels below the threshold values that may be a crucial factor to determine the presence of fetal heart malformations.     

Piperlongumine induces cell death through ROS-mediated CHOP activation and potentiates TRAIL-induced cell death in breast cancer cells

Purpose

Piperlongumine (PL) has been shown to selectively induce apoptotic cell death in cancer cells via reactive oxygen species (ROS) accumulation. In this study, we characterized a molecular mechanism for PL-induced cell death.

Methods

Cell viability and cell death were assessed by MTT assay and Annexin V-FITC/PI staining, respectively. ROS generation was measured using the H₂DCFDA. Small interfering RNA (siRNA) was used for suppressing gene expression. The mRNA and protein expression were analyzed by RT-PCR and Western blot analysis, respectively.

Results

We found that PL promotes C/EBP homologous protein (CHOP) induction, which leads to the up-regulation of its targets Bim and DR5. Pretreatment with the ROS scavenger N-acetyl-cysteine abolishes the PL-induced up-regulation of CHOP and its target genes, suggesting an essential role for ROS in PL-induced CHOP activation. The down-regulation of CHOP or Bim with siRNA efficiently attenuates PL-induced cell death, suggesting a critical role for CHOP in this cell death. Furthermore, PL potentiates TRAIL-induced cytotoxicity in breast cancer cells by upregulating DR5, as DR5 knockdown abolished the sensitizing effect of PL on TRAIL responses.

Conclusions

Overall, our data suggest a new mechanism for the PL-induced cell death in which ROS mediates CHOP activation, and combination treatment with PL and TRAIL could be a potential strategy for breast cancer therapy.     

The BRAF mutation is associated with the prognosis in colorectal cancer

Background

Two members of the Ras/Raf signaling pathway, KRAS and B-raf, are suspected to be involved in the stepwise progression of colorectal cancer (CRC) tumorigenesis.

Objective

We compared the KRAS and BRAF mutation status of CRC patients with their clinicopathological characteristics and examined the effect of mutation status on survival rates.

Methods

DNA was extracted from 164 samples, and the mutation statuses of KRAS and BRAF were assessed using peptide PNA clamp real-time PCR method. The presences of mutation were compared with clinicopathological factors and 5-year survival rate.

Results

Among the 164 CRC cases, KRAS mutation as detected in 71 cases (43.3 %), respectively, with no relationship with clinicopathological factors of the patients. On Kaplan–Meier survival analysis, KRAS mutation was not significantly associated with survival (p = 0.971). BRAF mutation was detected in 26 cases (15.9 %) and not associated with clinicopathological factors of the patients. However, the 5-year survival rate of BRAF mutations was significantly decreased (p = 0.02).

Conclusions

The presence of KRAS mutation did not correlate with the various clinicopathological factors of CRC patients or the survival rate. However, the survival rate was reduced in BRAF-mutated CRC patients. Therefore, BRAF mutation could be an important prognostic factor in CRC patients.     

The humoral immune system in inflammatory bowel disease

As there have been reports of differences in mean levels of serum immunoglobulins between patients with ulcerative colitis and Crohn's disease, serum IgG, IgA, and IgM were estimated in 158 patients with inflammatory bowel disease and the results correlated with the clinical features of the patients. Although a higher mean IgG level in ulcerative colitis compared to Crohn's disease was confirmed, no difference was found when the comparison was limited to patients with colonic Crohn's disease. Patients with either disease had higher mean IgM levels than controls, and the IgM levels were higher on treatment with corticosteroids and showed a tendency to rise in remission. IgG and IgM levels were also higher in both diseases if extraintestinal manifestations were present. It is concluded that if clinical features, particularly disease site, are taken into account, the overall immunoglobulin responses in these two diseases show no differences.     

Associations between functional TNFR2 196 M/R polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis

Several studies have examined the effects of tumor necrosis factor receptor (TNFR) 1 +38 A/G and TNFR2 196 M/R polymorphisms on susceptibility to RA and have reported conflicting results. The purpose of this study was to examine whether the TNFR1 +38 A/G and TNFR2 196 M/R polymorphisms are associated with RA susceptibility. We performed a literature search using the Medical Literature Analysis and Retrieval System Online and Embase citation indices, and conducted a meta-analysis to examine the association between the TNFR1 +38 A/G and TNFR2 196 M/R polymorphisms and RA. Our meta-analysis included a total of 13 studies from 11 articles, consisting of 11 studies of the TNFR2 polymorphism (2,092 cases and 1,483 controls), and two studies of the TNFR1 polymorphism (672 cases and 288 controls). The meta-analysis revealed a significant association between the TNFR2 196 RR genotype and RA risk (OR 1.737, 95 % CI 1.275–2.367, P = 4.6 × 10^?5). Stratification by ethnicity indicated an association between the TNFR2 196 RR genotype and RA in Europeans (OR 2.054, 95 % CI 1.305–3.232, P = 0.002), but not in East Asians (OR 1.596, 95 % CI 0.642–3.971, P = 0.314). Analysis using a homozygote contrast model showed the same pattern for the TNFR2 196 RR genotype in a European and East Asian population. However, no association was found between the TNFR1 +36 A/G polymorphism and RA in a European population. Our meta-analysis demonstrated that the functional TNFR2 196 M/R polymorphism is associated with susceptibility to RA in the European population.     

The DJ-1 protein as a candidate biomarker in obstructive sleep apnea syndrome

Background

Oxidative stress has a central role in the pathophysiology of obstructive sleep apnea syndrome (OSAS). The DJ-1 protein functions as a sensor of oxidative stress, acting both as a reactive oxygen species scavenger (ROS) and an antioxidative response regulator. The aim of our study is to determine the serum levels of DJ-1 in OSAS patients and assess possible correlations with their clinical, demographical, and biochemical characteristics.

Methods

The study included 120 subjects from the Sleep Disorder Laboratory of the University Hospital of Thessaly (100 males vs 20 females, mean age 48?±?10, Apnea–Hypopnea Index (AHI) >5 episodes per hour of sleep). Subjects underwent full-night polysomnography (PSG) followed by morning blood sampling. Serum DJ-1 levels were determined via ELISA kits. Statistical analysis was performed using SPSS 19.

Results

The median DJ-1 levels were 56.7 ng/mL (IQR, 34.9–99.3 ng/mL). Statistically significant correlations were detected between DJ-1’s levels and AHI (Spearman’s rho?=?0.189, P?=?0.04), Desaturation Index (DI; Spearman’s rho?=?0.239, P?=?0.012), and serum low-density lipoprotein (LDL) (Spearman’s rho?=??0.205, P?=?0.042).

Conclusions

DJ-1 may be a useful biomarker in OSAS due to its correlations with AHI and DI. The correlation with serum LDL warrants further investigation regarding possible implications in OSAS patients’ cardiovascular comorbidities.     

Diabetes mellitus among outpatients with COPD attending a university hospital

Type 2 diabetes mellitus is a common comorbidity of COPD, but there are still many doubts about the relation among diabetes and COPD. We retrospectively collected data from patients afferent to our Respiratory Diseases outpatient clinic at the Tor Vergata University Hospital between 2010 and 2012. The study population was analyzed by clusters of age, gender, body mass index (BMI), smoking status, lung function, concomitant pharmacologic therapies and comorbidities. The values of the association between variables were expressed as odds ratio. Data were adjusted for gender, age and possible confounding variables by Mantel–Haenszel method. We identified 493 patients with COPD. Ninety-two (18.7 %) patients were affected by type 2 diabetes mellitus, with no significant gender differences. The prevalence distribution was similar among the different age clusters, but the association was stronger in patients younger than 65 years. The association was present only in obese subjects in whom it was significant only in patients with moderate-to-severe COPD, but not mild COPD. The presence of cardiovascular diseases was significantly associated with diabetes mellitus in patients with COPD. There was a slight association of inhaled corticosteroid (ICS) use with the presence of diabetes mellitus in COPD, but the combination of an ICS with a β₂-agonist apparently reduced this association. The association with type 2 diabetes mellitus was greater in patients with COPD respect to general population, and correlated with the increase in BMI and the presence of other comorbidities, suggesting that both diseases may be targets of systemic inflammation.     

Cell mediated immunity and suppressor T cell function in children with cystic fibrosis

The relationship of general and suppressor T cell function to IgE sensitization was investigated in a group of 12 children with cystic fibrosis (CF) and 10 non-atopic control children. Increased IgE sensitization was noted in the cystic fibrosis group, as measured by increased group mean serum IgE levels and an increased incidence of multiple IgE skin sensitivities. Studies of active E rosettes, lymphocyte stimulation, delayed-type skin responsiveness, and Concanavalin A (Con A) induced suppressor cell function revealed no statistically significant group differences. The results of this study may implicate multiple mechanisms for IgE sensitization.     

Serum and intestinal fluid immunoglobulins in patients with giardiasis

To test the possibility that a factor predisposing to symptomatic giardiasis in the general population is immunoglobulin deficiency, we measured immunoglobulins in serum and intestinal fluids of 9 giardiasis patients (8 after eradication ofGiardia lamblia) and 12 healthy individuals. The concentrations of IgG, IgA, IgM, and IgE in serum and of IgA and IgM in intestinal fluids from the 2 groups were similar. Intestinal fluid IgG levels were significantly higher (P<0.1), however, in the patients (5.8±6.3 mg/100 ml) than in the control subjects (1.1±1.9 mg/100 ml). This difference was unexplained and is of uncertain biological significance. We conclude that giardiasis in generally healthy individuals is not etiologically related to unsuspected immunoglobulin deficiencies, even thoughG. lamblia infection is known to be very common in grossly immunoglobulin-deficient patients.     

Predictors of Mortality in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Background/Aim

Transarterial chemoembolization (TACE) is the recommended treatment for patients with Barcelona stage B hepatocellular carcinoma; however, community practice varies from these American Association for the Study of Liver Diseases guidelines. In this study, we sought to assess factors determining outcome after TACE and examine adherence to guidelines.

Methods

From January 2006 to December 2012, 308 patients with newly diagnosed HCC were treated at the Veterans Affairs (VA) Ann Arbor Healthcare System. Of these, 109 patients underwent TACE. The primary outcome measured mortality. Kaplan–Meier analysis was used to determine the cumulative probability of death. Cox regression was used to assess the predictors of mortality.

Results

The median age of the 109 patients was 60 years (48–90), 97 % were males and 82 % had chronic HCV infection. The median size of the largest lesion was 4 cm, 51 % were multifocal, and portal vein thrombosis was present in 3.6 %. Sixty-two patients died after median 333 days from the index TACE treatment. Median overall survival from index TACE was 11.2 months. Unadjusted 1-, 2-, and 3-year survival was 64, 35, and 24 %, respectively. CTP score (B vs. A: HR 2.51, p = 0.002; C vs. A: HR 7.96, p < 0.0001) and presence of complete response to TACE (HR 0.51, p = 0.004) were independent predictors of mortality. Barcelona stage (p = 0.88) and performance status as measured by ECOG (p = 0.98) were not associated with mortality after TACE.

Conclusions

In this community based, single VA center study, we found a significant number of patients beyond Barcelona stage B were treated with TACE. Advanced TNM stage, poor liver synthetic function and achieving CR with TACE were better predictors of mortality than guideline-directed decisions based on Barcelona stage. These factors may be useful to guide future patient selection for TACE.     

Sociodemographic and disease-related factors are associated with patient-reported anxiety and depression in spondyloarthritis patients in the Swedish SpAScania cohort

Anxiety and depression are common among patients with rheumatic diseases. This study aims to explore which factors are associated with self-reported anxiety and depression in a well-defined cohort of spondyloarthritis (SpA) patients. In 2009, 3,711 patients from the SpAScania cohort were sent a postal questionnaire to assess health-related quality of life (HRQoL) and physical and mental functioning. The Hospital Anxiety and Depression Scale measured anxiety (HADS-A) and depression (HADS-D), subscales 0–21, best–worst. HADS ≥8 indicates possible cases of anxiety or depression. One-way ANOVA (p?HADS scores. Linear regression analysis adjusted for age, gender, and disease duration was used to test for associations between HADS and independent variables. In total, 2,167 (58 %) patients (52 % females, mean age 55.4 years) returned the questionnaire. In total, 683 (32 %) cases were classified as “possible anxiety” and 305 (14 %) as “possible depression” cases with mean (SD) HADS-A 5.9 (4.3) and HADS-D 4.4 (3.6). There were no differences among the SpA subtypes in HADS-A and HADS-D. HADS-A and HADS-D were associated with lower education, lower physical activity (HADS-D only), chronic pain problems, more fatigue, lower general health, lower HRQoL, lower level of functioning, higher disease activity, and lower self-efficacy. Associations with anxiety and/or depression appear multifactorial in patients with SpA including both personal and disease-related factors. Since these comorbidities are increased in SpA and treatable, they should be screened for in clinical practice, possibly with instruments like the HADS.     

Prevalence of Uninvestigated Dyspepsia and Gastroesophageal Reflux Disease in Korea: A Population-Based Study Using the Rome III Criteria

Background/Aims

There have been few population-based studies on the prevalences of gastroesophageal reflux disease (GERD) and dyspepsia using Rome III criteria in Asian countries.

Methods

A population-based, cross-sectional study was conducted by telephone interviews of 5,000 Koreans between the ages of 20–69 years. Gastrointestinal symptoms were assessed by a translated Korean version of Rome III criteria. Uninvestigated dyspepsia (UID) was defined by symptom criteria of Rome III. GERD was defined by troublesome heartburn and/or acid regurgitation occurring at least once a week. The EQ5D assessment tool was used for the evaluation of quality of life.

Results

The prevalences of UID, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were 7.7, 5.6, and 4.2 %, respectively. Overlap between PDS and EPS was found in 27.1 % (104/384) of subjects with UID. There were no significant differences in demographic variables between patients with PDS and EPS. The prevalence of GERD was 7.1 %. Overlap between GERD and UID was found in 50.0 % of GERD patients. The EQ5D index of patients without either UID or GERD was 0.92 ± 0.07, and those of patients with only UID, with only GERD, and with both UID and GERD were 0.88 ± 0.09, 0.88 ± 0.11, and 0.84 ± 0.15, respectively.

Conclusions

GERD and UID based on Rome III criteria were prevalent and significantly affected the quality of life in Korea. In Korean patients with UID, there was considerable overlap and there were no significant differences in demographic variables between PDS and EPS.     

EGFR Mutation Testing Practice in Advanced Non-Small Cell Lung Cancer

Purpose

Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients.

Methods

An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients.

Results

24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79 % of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60 % of participants recommend waiting for EGFR test results prior to initiation of first-line therapy.

Conclusions

EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.     

PECAM-1 gene polymorphisms and soluble PECAM-1 level in rheumatoid arthritis and systemic lupus erythematosus patients: any link with clinical atherosclerotic events?

Genetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and <0.001). Soluble PECAM-1 level was significantly higher in RA patients than in SLE patients and healthy controls (p values <0.001). Atherosclerotic complications were more frequent in SLE patients with AG genotype (rs12953) than those with AA genotype (p?=?0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p?=?0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.