Placental volume at 11 to 14 gestational weeks in pregnancies complicated with fetal growth restriction and preeclampsia.

OBJECTIVE: The study aims to evaluate the predictive value of first trimester placental volume in pregnancies destined to develop fetal growth restriction (FGR) and preeclampsia (PE). METHODS: Prospective observational study including placentas from 34 FGR, 12 PE, 15 GH (gestational hypertension) pregnancies, and 265 controls. Placental volume (PV) was obtained using VOCAL technique, and a z score was calculated (z-PV). The association of PV with other first trimester variables and maternal characteristics was assessed with Spearman's correlation. RESULTS: PV increased exponentially with crown-rump length (CRL) and was unrelated to maternal factors (weight, age, parity, and smoking status) as well as first trimester uterine artery Doppler, free ß-hCG, nuchal translucency, or fetal heart rate. However, PV was positively associated with maternal height, CRL, PAPP-A, and birth weight. z-PV was a strong predictor for FGR with abnormal fetal Dopplers (AUC = 0.9472, P < 0.001). z-PV provided moderate prediction of FGR with normal fetal Dopplers (AUC = 0.8396, P < 0.001), PE (AUC = 0.8312, P < 0.001), and GH (AUC = 0.7640, P < 0.001). The addition of maternal weight, PAPP-A, ß-hCG, and uterine artery Doppler improved our models. CONCLUSION: At 11 to 14 weeks, PV is an independent predictor of pregnancy complications related to placental insufficiency, and the predictive ability is greater for FGR pregnancies with abnormal fetal Dopplers.

Cervical length at 11-40 weeks: unconditional and conditional longitudinal reference ranges.

INTRODUCTION: Our aim was to establish unconditional and conditional longitudinal reference ranges for cervical length throughout pregnancy. MATERIAL AND METHODS: Prospective longitudinal study. In singleton pregnancies repeated cervical length measurements were carried out by transvaginal ultrasound throughout gestation. Multilevel modeling was applied to establish cervical length reference ranges from 11 to 40 weeks. RESULTS: In all, 4397 women contributed to 13 765 cervical length measurements. A linear mixed effects random intercept-random slope model was fitted to the data. Mean cervical length had a negative non-linear polynomial association with gestational age. Unconditional ranges were developed. Terms that allow the construction of personalized cervical length charts conditional to a previous measurement were calculated. CONCLUSIONS: We constructed longitudinal reference charts for cervical length in singleton pregnancies. Cervical length should be adjusted according to specific gestational-age-dependent ranges. Individualization of cervical assessment is feasible by the application of charts conditional to previous measurements.

Maternal serum osteocalcin at 11-14 weeks of gestation in gestational diabetes mellitus.

BACKGROUND: Recent studies support that osteocalcin (OC), apart from its skeletal role, is implicated in glucose homoeostasis. Aims of this study were to examine the first-trimester maternal serum concentrations of OC in pregnancies that developed gestational diabetes mellitus (GDM) and to create a first-trimester prediction model for GDM. DESIGN: Case-control study in a prospective cohort of pregnant women. Maternal serum levels of OC were measured in 40 cases that developed GDM and 94 unaffected controls. First-trimester biophysical parameters, biochemical indices, maternal-pregnancy characteristics, and OC concentrations were assessed in relation to GDM occurrence. RESULTS: In the GDM group, first-trimester OC serum levels were increased compared to the control group (mean = 8·81 ng/mL, SD = 2·59 vs. mean = 7·34 ng/ml, SD = 3·04, P = 0·0058). Osteocalcin was independent of first-trimester biophysical and biochemical indices. Osteocalcin alone (OR = 1·21, CI: 1·02-1·43, P = 0·023) was a significant predictor of GDM [Model R(2) = 0·04, area under the curve (AUC) = 0·61, CI: 0·55-0·72, P < 0·001]. The combination of maternal and pregnancy characteristics with OC resulted in an improved prediction model for GDM (Model R(2) = 0·21, AUC = 0·80, CI: 0·71-0·88, P < 0·001). The combined model yields a sensitivity of 72·2% for 25% false-positive rate. CONCLUSIONS: First-trimester maternal serum levels of OC are increased in GDM pregnancies. Osteocalcin combined with maternal and pregnancy characteristics provides an effective screening for GDM at 11-14 weeks.

Towards detecting open spina bifida in the first trimester: the examination of the posterior brain.

INTRODUCTION: Our aim was to examine the value of indirect signs of open spina bifida in the mid-sagittal view of the posterior brain at the 11-13 weeks' ultrasound examination and to summarize the current evidence for the first-trimester diagnosis of spina bifida. METHODS: This was a prospective study in routine obstetric population. The presence of four almost parallel lines (four-line view) in the posterior brain was recorded. Biparietal diameter (BPD), intracranial translucency (IT) and cisterna magna (CM) were measured. The ratio of IT to CM (R ratio) was calculated. RESULTS: 2,491 pregnancies were examined prospectively. Updated reference ranges for IT and CM were constructed. There were 3 cases with open spina bifida, and the four-line view was abnormal in 2 of them. The abnormal fetuses had smaller BPD as well as pronounced reduction in the CM and increase in the R ratio. DISCUSSION: Examination of the posterior brain was feasible in all fetuses in the setting of the routine 11-13 weeks' ultrasound examination. Indirect signs of spina bifida are visible in the mid-sagittal view of the posterior brain, and the assessment of these structures can be a reliable tool in the early identification of this abnormality.

Elevated placental growth factor concentrations at 11-14 weeks of gestation to predict gestational diabetes mellitus.

OBJECTIVE: To examine maternal serum concentrations of placental growth factor (PlGF) at 11-14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. METHODS: Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal-pregnancy characteristics were analyzed. RESULTS: Log10 transformed PlGF (log10 PlGF) was not related to maternal factors. Log10 PlGF was increased (p=0.008) in the GDM group compared to the control group. Log10 PlGF was associated with fasting glucose levels (p=0.04) in the oral glucose tolerance test. Log10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group. Maternal weight and maternal age were the only predictors of GDM among the maternal factors [area under the curve (AUC)=0.73, p<0.001]. Log10 PlGF alone was a significant predictor of GDM (AUC=0.63, p<0.001). Combination of maternal weight, maternal age and log10 PlGF resulted in an improved prediction (DR=71.4%, for 25% FPR, AUC=0.78, Model R(2)=0.17, p<0.001). CONCLUSION: At 11-14weeks in pregnancies that develop GDM, the maternal serum levels of PlGF are increased. Measurement of serum PlGF at 11-14weeks improves the performance of early screening for GDM provided by maternal factors alone.

Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: molecular cytogenetic analysis, fetal pathology and review of the literature.

BACKGROUND: Partial trisomy of the long arm of chromosome 1 (1q) is an exceptionally rare chromosomal abnormality and most of the prenatally diagnosed cases are associated with either complete (q11-qter) or large (q21-qter) duplications with pre- or perinatal demise of all reported cases. The most common sonographic findings associated with this karyotype abnormality include ventriculomegaly, increased nuchal translucency or nuchal fold, renal and cardiac abnormalities, craniofacial dysmorphism, and limb deformities. However, there is a wide spectrum of clinical manifestations due to the great variability in the extent of the duplication size and the possible contribution of additional genetic rearrangements in the final phenotype. CASE REPORT: We report on a female fetus with sole partial trisomy 1q presenting with multiple structural malformations in the second trimester scan. Standard karyotyping demonstrated a large duplication on the proximal end of chromosome 1 [46,XX,dup(1)(pter→q31::q31→q12::q31→qter)] and further application of comparative genomic hybridization array confirmed the diagnosis and offered a precise characterization of the genetic defect. CONCLUSION: A fetus with nonmosaic partial trisomy 1q that was prenatally diagnosed upon multiple abnormal ultrasound findings is presented. A detailed review of the currently available literature on the prenatal diagnostic approach of partial trisomy 1q in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided. The use of novel molecular techniques such comparative genomic hybridization array could shed further light on the correlation between the genes identified in the chromosomal region of interest and the resultant phenotype.

Reproducibility study of fetal 3-D volumetry in the first trimester: effect of fetal size and rotational angle of VOCAL software.

Intra- and inter-observer reproducibility of fetal volume measurement by 3-D ultrasound scan (using VOCAL [Virtual Organ Computer-Aided Analysis] software) in 27 fetuses at 7 to 13 wk was studied. For intra-observer variability, the mean difference (MD) and 95% limits of agreement (95% LOA) at 12°, 18° and 30° were MD(12) = 0.097, 95% LOA(12) = -0.87 to +1.06; MD(18) = 0.07, 95% LOA(18) = -1.31 to +1.45; and MD(30) = -0.07, 95% LOA(30) = -1.55 to +1.41. The standard deviation of the differences (SD(DIF)) increased with crown-rump length at 12° (p = 0.0016), 18° (p = 0.0011) and 30° (p = 0.02). For inter-observer variability, MD(12) = 0.15, 95% LOA(12) = -1.65 to +1.95; MD(18) = 0.042, 95% LOA(18) = -1.79 to +1.87; and MD(30) = 0.19, 95% LOA(30) = -1.24 to +1.62. SDDIF increased with crown-rump length at 18° (p = 0.0084) and 30° (p = 0.0073). The accuracy of fetal volume measurement was not influenced by rotational angle or fetal size. Precision deteriorated for wider rotational angles and larger fetuses.

Fetal volume at 11-14 gestational weeks: reference ranges and association with first trimester biochemical and biophysical markers.

AIMS: To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11-14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters. METHODS: Prospective observational study on 240 fetuses at 11-14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided Analysis. Pearson correlation coefficient (cc) and regression analysis were used. RESULTS: FV increased exponentially with crown rump length and was unrelated to maternal weight (cc=-0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76), smoking status (t-test, P=0.149) and mode of conception (t-test, P=0.8). Z-scores (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=-0.026, P=0.733), log10 multiples of the median (MoM) free beta human chorionic gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was significantly positively correlated with log10 MoM pregnancy associated plasma protein-A (PAPP-A; regression coefficient=1.420976, R2=0.0957, P<0.0001). CONCLUSIONS: FV is strongly related to PAPP-A even after adjustment for crown rump length with a mechanism unrelated to placental perfusion. FV is independent of the vast majority of first trimester parameters; hence, it is a promising marker of early fetal growth.

Noninvasive prenatal diagnosis of Down syndrome: current knowledge and novel insights.

The noninvasive prenatal diagnosis of trisomy 21 (Down syndrome) is an actively researched area of prenatal medicine, as this is the most common aneuploidy compatible with life and a major cause of mental retardation. The isolation of intact fetal cells, and most importantly, the successful detection of fetal-origin nucleic acids (cell-free fetal DNA and RNA), in maternal plasma even from the early stages of pregnancy has inspired scientists to develop discriminative genetic markers for the prenatal detection of aneuploidy. In the near future, the development of epigenetic fetal-specific markers will possibly allow the universal application of a cell-free fetal DNA-based diagnostic test regardless of the gender of the fetus or its polymorphic status. Other promising approaches rely upon the detection of free placentally derived RNA transcribed from genes located on chromosome 21 and the application of highly sensitive techniques, such as digital polymerase chain reaction and high-throughput shotgun sequencing. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of fetal origin nucleic acids poses severe technical challenges. In this review article, we present an overview of the current knowledge in the field of noninvasive prenatal assessment of fetuses with Down syndrome and the future perspectives regarding new fetal markers and novel molecular techniques that may eventually be applied in the clinical setting as a valid and safe option for women who opt for noninvasive accurate prenatal diagnosis.

Maternal serum placental growth hormone at 11-13 weeks' gestation in pregnancies delivering small for gestational age neonates.

OBJECTIVE: To investigate whether the maternal serum concentration of human placental growth hormone (PGH) at 11-13 weeks' gestation is altered in pregnancies that deliver small for gestational age (SGA) neonates. METHODS: Maternal serum concentration of PGH was measured in 60 cases that subsequently delivered SGA neonates in the absence of preeclampsia and compared to 120 non-SGA controls. RESULTS: In the SGA group, compared to the non-SGA group, there was no significant difference in the median PGH MoM (0.95 MoM, IQR 0.60-1.30 vs. 1.00 MoM, IQR 0.70-1.30, p = 0.97). There was no significant association between PGH MoM and birth weight percentile in either the SGA (p = 0.72) or in the non-SGA group (p = 0.63). CONCLUSION: Maternal serum PGH at 11-13 weeks' gestation is unlikely to be a useful biochemical marker for early prediction of SGA.

Prenatal diagnosis of Wolf-Hirschhorn syndrome confirmed by comparative genomic hybridization array: report of two cases and review of the literature.

Wolf-Hirschhorn syndrome (WHS) is a well known genetic condition caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements lead to a wide spectrum of clinical manifestations. The majority of the reports of prenatally diagnosed WHS cases are associated with large 4p deletions identified by conventional chromosome analysis; however, the widespread clinical use of novel molecular techniques such as array comparative genomic hybridization (a-CGH) has increased the detection rate of submicroscopic chromosomal aberrations associated with WHS phenotype. We provide a report of two fetuses with WHS presenting with intrauterine growth restriction as an isolated finding or combined with oligohydramnios and abnormal Doppler waveform in umbilical artery and uterine arteries. Standard karyotyping demonstrated a deletion on chromosome 4 in both cases [del(4)(p15.33) and del(4)(p15.31), respectively] and further application of a-CGH confirmed the diagnosis and offered a precise characterization of the genetic defect. A detailed review of the currently available literature on the prenatal diagnostic approach of WHS in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided.

Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11-13 weeks' gestation in pregnancies delivering small for gestational age neonates.

OBJECTIVE: To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 at 11-13 weeks' gestation in the prediction of small-for-gestational age (SGA) neonates. STUDY DESIGN: Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls. RESULTS: In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4-93.4 ng/mL vs 94.9, IQR 56.7-131.2 ng/mL, p=0.002) and IGFBP-1 (58.2, IGR 39.8-84.9 ng/mL vs 81.4, IGR 57.3-105.5 ng/mL, p=0.002) but not IGFBP-3 (54.5, IGR 45.6-61.5 ng/mL vs 55.4, IGR 47.4-64.9 ng/mL, p=0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA. CONCLUSION: Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.

FGFR3 related skeletal dysplasias diagnosed prenatally by ultrasonography and molecular analysis: presentation of 17 cases.

Fibroblast Growth Factor Receptor 3 (FGFR3) related skeletal dysplasias are caused by mutations in the FGFR3 gene that result in increased activation of the receptors causing alterations in the process of endochondral ossification in all long bones, and include achondroplasia, hypochondroplasia, thanatophoric dysplasia, and SADDAN. Reports of prenatal diagnosis of FGFR3 related skeletal dysplasias are not rare; however, the correlation between 2nd trimester ultrasonographic findings and underlying molecular defect in these cases is relatively poor. There is a need for specific ultrasound (U/S) predictors than can distinguish lethal from non-lethal cases and aid an earlier prenatal diagnosis. Here we present one familial and 16 sporadic cases with FGFR3 related skeletal dysplasia, and we evaluate biometric parameters and U/S findings consistent with the diagnosis of skeletal dysplasia. U/S scan performed even at the 18th week of gestation can indicate a decreased rate of development of the femora (femur length (FL) <5th centile), while the mean gestational age at diagnosis is still around the 26th week. The utility of other biometric parameters and ratios is discussed (foot length, BPD, HC, FL/foot, and FL/AC). Prenatal cytogenetic and molecular genetic analyses were performed. A final diagnosis was reached by molecular analysis. In two cases of discontinued pregnancy, fetal autopsy led to a phenotypic diagnosis and confirmed the prenatal prediction of lethality. We conclude that the combination of U/S and molecular genetic approach is helpful for establishing an accurate diagnosis of FGFR3-related skeletal dysplasias in utero and subsequently for appropriate genetic counselling and perinatal management.

Recent advances in optical imaging for cervical cancer detection.

Cervical cancer is one of the most common and lethal gynecological malignancies in both developing and developed countries, and therefore, there is a considerable interest in early diagnosis and treatment of precancerous lesions. Although the current standard care mainly based on cytology and colposcopy has reduced rates of cervical cancer morbidity and mortality, many lesions are still missed or overcalled and referred for unnecessary biopsies. Optical imaging technologies, spectroscopy approaches and high-resolution imaging methods are anticipated to improve the conventional cervical cancer screening providing in vivo diagnosis with high sensitivity and specificity. Their concept is that morphologic and biochemical properties of the cervical tissue are altered in response to its malignant transformation. In addition, contrast agents that target against specific neoplastic biomarkers can enhance the effectiveness of this new technology. Due to the unprecedented growth of these optical techniques accompanied probably by favorable cost-effectiveness, the primary detection of premalignant lesions may become more accessible in both the developing and the developed countries and can offer see-to-treat workflows and early therapeutic interventions.

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks in trisomy 21 and trisomy 18 pregnancies.

OBJECTIVE: To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 in first-trimester screening for fetal aneuploidies. STUDY DESIGN: Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation were measured and compared in 30 trisomy 21, 30 trisomy 18 and 120 euploid pregnancies. RESULTS: The median multiple of the normal median (MoM) values of maternal serum IGF-I, IGFBP-1 and IGFBP-3 in trisomy 21, trisomy 18 and euploid pregnancies were not significantly different (IGF-I: 1.10, 1.14 and 1.0 MoM, respectively; IGFBP-1: 1.10, 1.01 and 1.0 MoM; IGFBP-3: 0.90, 1.16 and 0.98 MoM). CONCLUSION: Measurement of maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation is unlikely to be useful in screening for trisomies 21 and 18.

Maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) at 11-13 weeks in pre-eclampsia.

OBJECTIVE: The aim of this study was to determine the maternal serum concentration of insulin-like growth factor-binding protein-1 (IGFBP-1) at 11-13 weeks' gestation in pregnancies that subsequently develop pre-eclampsia (PE) and to examine the possible association with uterine artery pulsatility index (PI). METHODS: Maternal serum concentration of IGFBP-1 and uterine artery PI were measured in 60 cases that developed PE, including 20 that required delivery before 34 weeks (early-PE) and 120 unaffected controls. The measured IGFBP-1 concentration and uterine artery PI were converted into a multiple of the expected median (MoM) in unaffected pregnancies and median MoM values were compared in the outcome groups. Regression analysis was used to determine the significance of association of IGFBP-1 MoM with uterine artery PI MoM. RESULTS: In the early- and late-PE groups, the median IGFBP-1 was decreased (0.63 and 0.67 MoM, respectively) and uterine artery PI was increased (1.31 and 1.19 MoM, respectively). In the group that developed PE there were no significant associations between serum IGFBP-1 with uterine artery PI (p = 0.210). CONCLUSION: In pregnancies that develop PE, the serum IGFBP-1 is decreased from the first trimester suggesting that IGFBP-1 may be implicated in the pathogenesis of PE in a mechanism unrelated to impaired placental perfusion.

Maternal serum human placental growth hormone (hPGH) at 11 to 13 weeks of gestation in preeclampsia.

OBJECTIVE: Human placental growth hormone (hPGH) is produced by human placenta and plays a central role in the maternal metabolic adjustments to pregnancy. The objective of this study was to investigate the maternal serum concentration of hPGH at 11-13 weeks of gestation in pregnancies that subsequently developed preeclampsia (PE), and to examine the possible association with uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A). METHODS: The maternal serum concentration of hPGH at 11-13 weeks was measured in a case-control study from 60 cases that developed PE and 120 unaffected controls. The measured hPGH concentration was converted into a multiple of the expected median (MoM) in unaffected pregnancies. Regression analysis was used to determine the significance of association between hPGH MoM with uterine artery PI MoM and PAPP-A MoM. RESULTS: In the pregnancies that subsequently developed PE the median serum hPGH concentration was not significantly different from that in the unaffected group (0.92 versus 1.00 MoM), whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no significant association between serum hPGH MoM and gestational age at delivery, uterine artery PI MoM, or serum PAPP-A MoM. CONCLUSION: The finding that in the PE group serum hPGH level during the first trimester is normal suggests that it is unlikely that this hormone plays a role in the pathogenesis of PE.

Maternal serum insulin-like growth factor-I at 11-13 weeks in preeclampsia.

OBJECTIVE: To investigate the maternal serum concentration of insulin-like growth factor-I (IGF-I) in the first trimester of pregnancies that subsequently develop preeclampsia (PE) and to examine the possible association with uterine artery pulsatility index (PI). METHODS: The maternal serum concentration of IGF-I and uterine artery PI at 11-13 weeks were measured in 53 cases that developed PE, including 18 that required delivery before 34 weeks (early-PE) and 106 unaffected controls. The measured IGF-I concentration and uterine artery PI were converted into a multiple of the expected median (MoM) in unaffected pregnancies, and median MoM values were compared in the outcome groups. The significance of association of IGF-I MoM with uterine artery PI MoM was determined by regression analysis. RESULTS: In the early-PE and late-PE groups, compared to the unaffected controls, the median IGF-I decreased (0.53 and 0.55 MoM, respectively) and uterine artery PI increased (1.55 and 1.21 MoM, respectively). In the group that developed PE, there was no significant association between serum IGF-I and uterine artery PI (p = 0.632). CONCLUSION: In pregnancies destined to develop PE, the circulating levels of IGF-I decrease from the first trimester of pregnancy suggesting that IGF-I may be implicated in the pathogenesis of the disease.

Expression analysis of Akt and MAPK signaling pathways in lung tissue of patients with idiopathic pulmonary fibrosis (IPF).

PURPOSE OF THE STUDY: Several studies in patients with lung cancer have shown that epidermal growth factor receptor regulates various tumorigenic processes through the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin and Ras/Raf/Mek/Erk (mitogen-activated protein kinase (MAPK)) signalling pathways. The aim of our study is to evaluate whether these pathways are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and to seek indirect evidence of a common pathogenetic pathway with lung cancer. m-RNA expression of oncogenes participating in these two signaling pathways, as well as the combined m-RNA expression of the suppressor genes R-kip and p53 in lung tissue of patients with IPF were evaluated. BASIC PROCEDURES: The study population was composed by two distinct groups. Patients with IPF (n = 25) and control subjects who underwent thoracic surgery for reasons other than interstitial lung disease (n = 10). Expression analysis of the aforementioned oncogenes and suppressor genes was performed using real-time reverse transcription polymerase chain reaction. MAIN FINDINGS: We found no difference in the overall m- RNA expression between controls and IPF in both investigated pathways. However, Braf has been overexpressed in IPF samples (P = 0.01) in contrast with K-ras that has been found downregulated (P < 0.001) in comparison with controls. PRINCIPAL CONCLUSIONS: These findings cannot exclude the hypothesis of involvement of Akt and MAPK signalling pathways in pathogenesis of IPF. However, further investigation is needed in order to verify these data.