Theta-band Connectivity within Cognitive Control Brain Networks Suggests Common Neural Mechanisms for Cognitive and Implicit Emotional Control.

Self-control is a core aspect of adaptive human behavior. It allows the attainment of personal goals by regulating unwanted thoughts, emotions, and behavior. Previous research highlighted the crucial role of cognitive control for explicitly pursued self-control and explicit emotion regulation strategies (such as cognitive reappraisal or attentional distraction). The present study investigated whether similar neural mechanisms would be involved in an implicit self-control task that acted as a covert emotion regulation strategy. Thirty-six female participants unscrambled sentences of either neutral (no-regulation condition) or neutral and self-control-related content (regulation condition) before passively viewing negative and neutral pictures. Compared with the no-regulation condition, implicit induction of self-control reduced the amplitude of the late positive potential to negative pictures, indicating successful emotion downregulation. Crucially, implicit self-control enhanced connectivity within the two cognitive control brain networks in the theta frequency band. Specifically, for the frontoparietal network, increased connectivity from the dorsolateral PFC to the intraparietal cortex was observed. For the cingulo-opercular network, increased connectivity from dorsal anterior cingulate cortex to the left anterior insula/frontal operculum and from the right anterior insula/frontal operculum to the dorsal anterior cingulate cortex was observed. These effects were accompanied by a decrease in prestimulus alpha power in the right primary visual cortex, suggesting adjustment of attentional and perceptual processes in preparation for the upcoming affective stimulation. Together, our results indicate that self-control enhances cognitive control that is necessary for setting, maintaining, and monitoring the achievement of self-control behavior, as well as regulation of attentional and emotional processes.

Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer.

Kinase inhibitors (KIs) represent a growing class of drugs directed at various protein kinases and used in the treatment of both solid tumors and hematologic malignancies. It is a heterogeneous group of compounds that are widely applied not only in different types of tumors but also in tumors that are positive for a specific predictive factor. This review summarizes common cardiotoxic effects of KIs, including hypertension, arrhythmias with bradycardia and QTc prolongation, and cardiomyopathy that can lead to heart failure, as well as less common effects such as fluid retention, ischemic heart disease, and elevated risk of thromboembolic events. The guidelines for cardiac monitoring and management of the most common cardiotoxic effects of protein KIs are discussed. Potential signaling pathways affected by KIs and likely contributing to cardiac damage are also described. Finally, the need for further research into the molecular mechanisms underlying the cardiovascular toxicity of these drugs is indicated.

To remember, or not to remember? Potential impact of memory modification on narrative identity, personal agency, mental health, and well-being.

Memory modification technologies (MMTs)-interventions within the memory affecting its functions and contents in specific ways-raise great therapeutic hopes but also great fears. Ethicists have expressed concerns that developing and using MMTs may endanger the very fabric of who we are-our personal identity. This threat has been mainly considered in relation to two interrelated concerns: truthfulness and narrative self-constitution. In this article, we propose that although this perspective brings up important matters concerning the potential aftermaths of MMT utilization, it fails to tell the whole story. We suggest that capturing more tangible potential consequences of MMT use, namely, its psychological ramifications is crucial both in ethical considerations and in making decisions regarding the permissibility of such interventions. To this end, we first examine what current MMTs are capable of and what are the prospects of emerging MMTs. Subsequently, we outline the relationship between memory and personal identity; specifically, we indicate that concepts of self-defining memories and narrative identity are crucial to considering how MMTs may influence one's psychological functioning. On this basis, we analyze potential consequences of narrative disruption that may be the result of the use of MMTs; more precisely, we consider its potential effects on mental health, well-being, and personal agency, and outline the ethical dilemmas that decision-makers face in this context. We conclude by considering the broader cultural context that may have influence on policymaking regarding permissibility of memory modification interventions.

Relationship between Gd-IgA1 and TNFR1 in IgA nephropathy and IgA vasculitis nephritis in children - multicenter study.

AIM OF THE STUDY: To evaluate the relationship between serum Gd-IgA1 (sGd-IgA1) and serum and urine TNFR1 (sTNFR1, uTNFR1) levels as possible prognostic factors in IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN). MATERIAL AND METHODS: From 299 patients from the Polish Registry of Pediatric IgAN and IgAVN, 60 children (24 IgAN and 36 IgAVN) were included in the study. The control group consisted of 20 healthy children. Proteinuria, haematuria, serum creatinine as well as IgA and C3 levels were measured and glomerular filtration rate (GFR) was calculated at onset and at the end of the follow-up. Kidney biopsy findings were evaluated using the Oxford classification. Serum Gd-IgA1 and serum and urine TNFR1 levels were measured at the end of follow-up. RESULTS: Serum Gd-IgA1 level was significantly higher in IgAN and IgAVN patients in comparison to the control group. Urine TNFR1 was significantly higher in IgAN than in IgAVN and the control group. We did not observe any differences in sTNFR1 level between IgAN, IgAVN and control groups. We found a positive correlation between Gd-IgA1 and creatinine (r = 0.34), and negative between Gd-IgA1 and GFR (r = -0.35) at the end of follow-up. We observed a negative correlation between uTNFR1/creatinine log and albumin level and protein/creatinine ratio. We did not find any correlations between Gd-IgA1 and TNFR1. CONCLUSIONS: The prognostic value of sGd-IgA1 in children with IgAN and IgAVN has been confirmed. TNFR1 is not associated with Gd-IgA1 and is not a useful prognostic marker in children with IgAN/IgAVN and normal kidney function.

The dynamics of pain reappraisal: the joint contribution of cognitive change and mental load.

This study was designed to investigate the neural mechanism of cognitive modulation of pain via a reappraisal strategy with high temporal resolution. The EEG signal was recorded from 29 participants who were instructed to down-regulate, up-regulate, or maintain their pain experience. The L2 minimum norm source reconstruction method was used to localize areas in which a significant effect of the instruction was present. Down-regulating pain by reappraisal exerted a robust effect on pain processing from as early as ~100 ms that diminished the activity of limbic brain regions: the anterior cingulate cortex, right orbitofrontal cortex, left anterior temporal region, and left insula. However, compared with the no-regulation condition, the neural activity was similarly attenuated in the up- and down-regulation conditions. We suggest that this effect could be ascribed to the cognitive load that was associated with the execution of a cognitively demanding reappraisal task that could have produced a general attenuation of pain-related areas regardless of the aim of the reappraisal task (i.e., up- or down-regulation attempts). These findings indicate that reappraisal effects reflect the joint influence of both reappraisal-specific (cognitive change) and unspecific (cognitive demand) factors, thus pointing to the importance of cautiously selected control conditions that allow the modulating impact of both processes to be distinguished.

High Ki-67 expression is a marker of poor survival in apocrine breast carcinoma.

Apocrine carcinoma is a very rare type of breast cancer, which represents 0.5-4% of all breast cancers. The aim of the study was to analyze biological and clinical features of apocrine carcinoma and their influence on patients survival. The studied group consists of 57 patients, who underwent treatment between 1987 and 2010. Expression of ER, PgR, HER2, AR, GCDFP-15, EGFR, CK 5/6, CK 8/18 and Ki-67 was assessed immunohistochemically on formalin-fixed paraffin-embedded tissue sections. Presence of emboli and extent of lymphocyte infiltration were assessed on haematoxylin-eosin-stained slides. In the investigated group, 16 cases were ER/PgR positive and 49 were AR-positive. ER/PgR-negative tumours were often characterised by CK5/6 and EGFR positivity. The presence of AR was related to HER-2 and GCDFP-15 expression and tumours with expression of CK5/6 were more likely be EGFR positive and had higher Ki-67 LI. Higher probability of 10-years OS and DFS was observed in patients with tumours characterized by Ki-67 LI < 20% (p = 0.036 and p = 0.009, respectively). Favourable trend in OS was noted for patients with smaller tumours (p = 0.053), without lymph node metastases (p = 0.074) and without EGFR expression (p = 0.060). In apocrine breast carcinoma expression of Ki-67 is one of the most important factors influencing patients' survival.

Comparison of mutation profile between primary phyllodes tumors of the breast and their paired local recurrences.

Phyllodes tumor of the breast (PTB) is a rare neoplasm and accounts for 0.2-2.0% of breast cancer in women. Histopathological diagnosis of the tumor is difficult, and histological features do not always predict the course of the disease and the risk of progression. Pathogenesis and molecular biological characteristics as well as PTB prognostic factors are unknown. In search for genetic factors affecting PTB progression, 10 patients were analyzed for whom material from the primary tumor and local recurrence was available. DNA isolated from paraffin blocks was sequenced using the next-generation sequencing method (NGS). In 4 pairs, consisting of primary tumor and local recurrence, probably pathogenic/pathogenic variants were detected, and in three pairs they were observed in the CDKN2A gene, while other variants were found in PTEN and TP53 genes. NGS results indicate that the above-mentioned variants are hereditary, which suggests that the CDKN2A gene might be involved in cancerogenesis of PTB. Additionally, the selected pathogenic variant of EGFR gene was exclusively detected in one recuurent tumor, which might suggest the involvement of this gene in the mechanism of progression. In order to determine if this variant is associated with progression, the frequency of this mutation should be examined in larger group of malignant and borderline tumors.

Synovial sarcoma of the stomach: case report and systematic review of the literature.

Synovial sarcoma is a rare mesenchymal malignant neoplasm that presents a specific t(X;18) translocation forming SS18(SYT)-SSX chimera gene. It is most commonly seen in soft tissues of the extremities. The digestive tract is an exceptional site of involvement. We report a case of primary gastric synovial sarcoma in a 48-year-old female. Differential diagnosis of synovial sarcoma from other spindle cell, mesenchymal and cytokeratin-positive tumors is critical for the treatment and prognosis. Immunohistochemistry studies and molecular analysis are required to settle a proper diagnosis.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

Comet assay is not useful to predict normal tissue response after radiochemotherapy in cervical and larynx cancer patients.

Normal tissues reactions after radiotherapy vary considerably even between patients receiving the same treatment. The ability to predict the differences in radiosensitivity before radiotherapy would have important implication. Patients with squamous cell carcinoma of the: (i) cervix (38 patients) and (ii) larynx (19 patients) were studied. Control group consisted of 9 healthy women. To assess individual radiosensitivity/chemoradiosensitivity alkaline version of comet assay was performed using isolated peripheral blood lymphocytes from cancer patients and healthy donors. The level of endogenous (0Gy), initial (immediately after 6Gy irradiation) and residual (after irradiation and 1h of repair) DNA damage was investigated. The mean value of endogenous damage was similar in control and cervical cancer (CCU) groups and significantly lower than in larynx cancer patients. Cancer patients showed slower DNA repair. For CCU and larynx patients, comet assay parameters were not helpful for unequivocal prediction of appearance of acute and late radiation reaction effects. Comet assay seems to be unable to predict normal tissue reaction after radiochemotherapy. Therefore, there is still need for developing predictive assays, however, due to complicated mechanism of chemoradiosensitivity, only assays assessing not one but many molecular pathways might gives us reliable score.

[Influence of intensity, localization and type of deposits in renal biopsy for disease symptoms and follow up in children with IgA nephropathy]. / Wplyw nasilenia, lokalizacji i rodzaju zlogów w biopsji nerki na objawy kliniczne i rokowanie u dzieci z nefropatia IgA.

IgA nephropathy is the most common glomerulonephritis in the world. For diagnosis kidney biopsy is necessary. AIM: The aim of the study was assessment the significance of IgA, C3 and IgG deposits intensity and location in kidney childhood IgA nephropathy (IgAN) for the symptoms of the disease and the follow up. MATERIALS AND METHODS: Study population consisted of 81 children, average 11,45±3,99 years. IgAN was recognized based on renal biopsy, performed 1,2±1,84, median 0,5 years after the onset. We used Oxford classification (OC) to assess the severity of histopatological lesions. In renal biopsy IgA and C3 deposits were found in immunofluorescence in mesangium or in vessels of glomeruli or both, and intensity was defined 0 to +4. We analyzed: proteinuria (mg/kg/day), hematuria, creatinine, GFR (according to Schwartz formula) two times, at the onset of the disease (OOD) and at the follow up (FU). Patients were treated with: ACEI/ARB or steroids alone or with imunossupresion drugs: azathioprine (AZA), cyclophosphamide (CYC), cyclosporine A (CsA), mycopnenolate mophetil (MMF). The follow up was 3,31±2,88 years. We divided the patients into two groups, depending on the intensity of IgA deposits: G1 n=29 (+1/+2), G2 n=52 (+3/+4); depending on the localizations of these deposits, we analyzed 3 groups: A n= 39 (mesangium), B n= 15 (glomeruli vessels), C n=27 (both) and depending on the kind of deposits we analyzed 4 groups: gr. a - n=30 (only IgA), gr. b - n=37 (IgA+C3), gr. c - n=5 (IgA+IgG) gr. d - n= 9 (IgA+IgG+C3). RESULTS: At OOD and FU we not found any differences in G1 vs G2 for: age, proteinuria, GFR and OC in renal biopsy; at FU GFR<90 ml/ min/1,73 m2 FU was observed more frequently in G2 vs G1 (p=0,02). The differences in groups A,B,C and groups a,b,c,d were not found. CONCLUSIONS: Poor prognosis in childhood IgAN may also depend on the intensity of the deposits, irrespective of their location.

What has changed in the prevalence of hypertension in dialyzed children during the last decade?

BACKGROUND: Hypertension very often accompanies progression of chronic kidney disease (CKD) in children. A cross-sectional analysis of hypertension prevalence in dialyzed children in Poland was designed with a comparison with the data previously recorded 10 years earlier. METHODS: Two cohorts of children were analyzed: 59 subjects dialyzed in 2013, and 134 children from the previous study performed in 2003 that were reevaluated according to the current methodology. The incidence of hypertension (defined by SDS of sBP or dBP >1.64), clinical data, medical history, dialysis modalities and selected biochemical parameters of dialysis adequacy were analyzed. RESULTS: The prevalence of hypertension increased from 64% in 2003 to 78% in 2013. The efficacy of antihypertensive treatment remained unsatisfactory (61% proper BP control). Preservation of residual urine output and strict fluid balance may prevent development of hypertension in children on dialysis. CONCLUSIONS: Despite the higher awareness of hypertension and its complications in dialyzed children, the incidence of this entity has increased during the last decade, with the percentage of undertreated patients comparable to that observed 10 years ago. Thus, more attention should be paid to therapy efficacy in this population to prevent further damage to the cardiovascular system and to decrease morbidity.

Gender-related prognostic significance of clinical and biological tumor features in rectal cancer patients receiving short-course preoperative radiotherapy.

AIM: To study the prognostic value of clinical and biological features of rectal cancer and potential gender differences in patients' overall survival (OS), local recurrence-free survival (RFS) and metastasis-free survival (MFS) after short-course preoperative radiotherapy (SCRT) with short or long interval between RT and surgery (break). BACKGROUND: The length of the interval between RT and surgery in SCRT is debatable and gender-related differences in patients survival are not established yet. MATERIALS AND METHODS: 126 patients received SCRT with 5 Gy dose per fraction during 5 days, followed by radical surgery after short break ≤17 days, and a long break >17 days. Pretreatment tumor proliferation (bromodeoxyuridine labeling index, BrdUrdLI and S-phase fraction) was evaluated by flow cytometry and proteins: CD34, Ki-67, GLUT-1, Ku70, BCL-2, P53 expression was studied immunohistochemically. RESULTS: The studied group included 84 men and 42 women. There were 33, 76, and 17 cTNM (AJCC) tumor stages I, II, III, respectively. The median follow-up time was 53.3 months (range 2-142 months). For the whole group Cox multivariate analysis revealed that tumor grade (G > 1), interval between RT and surgery >17 days, pTNM stage >1 and P53 positivity + BrdUrdLI > 7.9% were negative prognostic factors for OS. Tumor aneuploidy and MVD > 140.8 vessels/mm2 were important for RFS. pTNM stage > 1 and P53 positivity combined with BrdUrdLI > 7.9% were risk predictors for MFS. Based on tumor biological features, gender-related difference in OS, RFS, and MFS were observed. In multivariate analysis, male patients age > 62 years and break >17 days only appeared to be significant for OS. CONCLUSIONS: In male rectal patients treated with SCRT, breaks between RT and surgery >17 days should be avoided because they negatively influence patients' survival.

The tumour border on contrast-enhanced spectral mammography and its relation to histological characteristics of invasive breast cancer.

Contrast-enhanced spectral mammography (CESM) is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: (1) their diagnostic usefulness, and (2) the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular). Therefore, we studied the relationship between the tumour margin assessed on CESM and (1) tumour borders defined on the basis of macroscopic and microscopic examination, (2) pT, (3) pN, and (4) tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1) macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004), (2) pT (p = 0.016), and (3) pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045). Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM), both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.

Gender-related significance of time interval between radiotherapy and surgery in hypofractionated preoperative radiotherapy for rectal cancer patients' survival.

AIM AND BACKGROUND: An optimal break between radiotherapy (RT) and surgery in short-course of RT (SCRT) for locally advanced rectal cancer is not clearly established. The aim of the study was to investigate the influence of the break in the preoperative SCRT and overall treatment time (OTT) for locally advanced rectal cancer patients (whole group and male/female subgroups) on patients overall survival (OS), recurrence-free survival (RFS), metastasis-free survival (MFS). MATERIALS AND METHODS: 131 patients were treated with SCRT (5 Gy/5 days), followed by surgery 3-53 days later. Break was calculated as the time interval between the end of irradiation to surgery and OTT as time interval from the beginning of RT to surgery. RESULTS: Mean break was 21.5 (range 3-53.0) days and mean OTT was 26.5 (range 7-58.0) days. In univariate analysis, a break longer than 15 days and OTT >23 days were negative prognostic factors for OS for all patients, and particularly for the male patients' subgroup. RFS was non-significantly higher (P = 0.066) for patients treated with a break ≤15 days and OTT ≤23 days (P = 0.099), irrespectively of patients' sex. Patients treated with a break longer than 15 days and OTT >23 days had non-significantly lower level of MFS than those treated with a shorter break (P = 0.269) and OTT ≤23 days (P = 0.498). CONCLUSION: In SCRT, a break in the treatment longer than 15 days, especially in the male patients subgroup, should be avoided, because it negatively affects patients' survival.

Comparison of eight commercially available kits for DNA extraction from formalin-fixed paraffin-embedded tissues.

A proper extraction method from formalin-fixed paraffin-embedded (FFPE) blocks is essential to obtain DNA of satisfactory quality/quantity. We compared the effectiveness of eight commercially available kits for DNA extraction based on 10 FFPE tissues. Kits differed significantly in terms of DNA yield, purity, and quality. Using the QIAamp DNA FFPE Tissue Kit (Qiagen) and the ReliaPrep FFPE gDNA Miniprep System (Promega), we obtained DNA of the highest quality and acceptable quantity. We also demonstrated that overnight digestion of samples usually improved DNA yield and/or purity. For precious or limited material, double elution is recommended for obtaining up to 42% higher amount of DNA.

Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy.

BACKGROUND: The aim of this study was to evaluate the usefulness of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio for predicting histological severity of kidney lesions in children with IgA nephropathy (IgAN) based on World Health Organization (WHO) and the Oxford classification (OC). METHODS: We studied 89 children with IgAN with a mean age of 11.38 ± 4.1 years (range 2-18 years). Based on available medical records, we retrospectively evaluated clinical data, IgA/C3 ratio, and kidney biopsy findings using the five-grade WHO classification and the OC The mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy/interstitial fibrosis (T) (MEST) score (absent = 0, present = 1) calculated as the sum of M+E+S+T ranging from 0 to 4. RESULTS: Mean IgA/C3 ratio values were significantly higher (P < 0.05) in patients with M1, S1, and T1 compared with M0, S0, and T0, respectively (P < 0.05); there were no differences in the WHO classification. We found a significant positive correlation between the IgA/C3 ratio and proteinuria (r = 0.24) and determined optimal cutoff values of the IgA/C3 ratio, with a corresponding confidence interval for specific MEST scores. CONCLUSIONS: The IgA/C3 ratio in children with IgAN may be a useful marker of the severity of lesions found in kidney biopsy as evaluated using the OC.

Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

UNLABELLED: Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. CONCLUSIONS: 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting.

Resistance to trastuzumab in patients with HER2-overexpressing breast cancer is associated with higher risk of progression or cancer death, and might be related to activation of PI3K/AKT/mTOR and Ras/Raf/MAPK signaling cascades and a decreased level of their inhibitor (PTEN). HER2-overexpressing breast cancer patients (n=75) treated with radical local therapy and trastuzumab in adjuvant setting were included into the study. Deoxyribonucleic acid isolated from paraffin sections was used to assess mutational status of the PIK3CA gene (p.H1047R and p.E545K mutations) by the quantitative polymerase chain reaction technique. Expression of selected proteins (ER, PgR, AR, Ki-67, EGFR) was assessed using immunohistochemistry. In the studied group we found significantly higher Ki-67LI in EGFR-positive carcinomas (p=0.048). Moreover, EGFR immunonegativity was observed more frequently in low-grade (G1/G2) carcinomas as well as in estrogen/progesterone and androgen receptor immunopositive tumors (p=0.042, p=0.016, p=0.044, respectively). Favorable metastasis-free survival was observed in patients with pN0 and pN1 (vs. pN2+3) stage (p=0.040) and with tumors characterized by low Ki-67LI (≤50% vs. >50%) (p=0.014). Patients with tumor androgen receptor immunonegativity (weak or lack of expression) or strong PTEN expression survived 3 years without metastases (p=0.007). The results of our study suggest that androgen receptor and PTEN status might be considered as indicators of trastuzumab sensitivity.

Distribution of podoplanin-positive tumor vessels predicts disease-specific survival of node-positive breast cancer patients treated with anthracyclines and/or taxanes.

We analyzed survival of 102 invasive ductal, node positive breast cancer patients, treated with surgery and adjuvant chemotherapy (anthracyclines and/or taxanes) with relation to: (a) well-known clinicopathological parameters, (b) MIB-1 labeling index (LI), (c) the distribution of podoplanin-positive vessels (DPV), expression of: (d) basal markers, and (e) fascin. Lower progression risk was found for patients with tumors characterized by (i) pN1 + pN2, (ii) MIB-1LI ≤ 28%, (iii) lack of lymphatic vessels or high tumor DPV than for patients with pN3, MIB-1LI > 28%, low DPV, respectively. Cox multivariate analysis revealed that both pN3 and low DPV were negative prognostic indicators.