Search

Listeria monocytogenes is a foodborne pathogen well known for its adaptability to diverse environment and host niches and its high fatality rate among infected immunocompromised populations. Infection in the immunocompetent host occurs but risk factors for the disease primarily points to abnormalities in cell-mediated and innate immunity as major predispositions to listeriosis. After ingestion of contaminated food, this pathogen is able to cross the intestinal, blood-brain and placental barrier and leads to gastroenteritis, meningitis and maternofetal infections which may result in abortion and spontaneous stillbirth. Despite the extensive use of this bacterium in the study of cell-mediated immunity and intracellular growth, our understanding of the host, pathogen and environmental factors that impact the pathogenesis of listeriosis is still incomplete. This review will summarize current knowledge, including our own efforts, about pathogen, host and environmental factors that influence, and contribute to the pathogenesis of Listeria monocytogenes infection.

Abstract Primary angiosarcoma of the breast is a rare tumour that account for fewer than 0.05% of all malignant mammary tumours. Angiosarcoma may have an perfidious clinical onset. Radiologic findings are often nonspecific and may appear completely normal in one-third of cases with primary angiosarcoma. The prognosis is usually poor because of the high rates of local recurrence and early development of metastases. Aggressive surgical resection is the mainstay of treatment. The role of adjuvant therapy has not yet been well established. Here we present a case of a 53 year old, postmenopausal women with primary angiosarcoma arising in fibroadenoma. To our knowledge, this is the first case described in the literature to date.

Background: Triple-negative breast cancer (TNBC) has the worst prognosis and the highest immunogenic potential of all breast cancer subtypes. It is characterized by a lack of estrogen and progesterone receptors as well as HER2. A major component of the tumor microenvironment (TME) of TNBC is tumor-infiltrating lymphocytes (TILs). A chaperone heat shock protein 70 (HSP70) is involved in several pathways that enable tumour growth and progression, as well as in immune modulation., Methods: Immunohistochemical analysis of HSP70 expression in immune cells, as well as expression of immunosuppressive markers CTLA4 and PD-L1 and major TILs components: CD8, CD4 and Tregs were analyzed in the superficial and deep tumor layer of primary TNBC and compared with established clinicopathological parameters. Clinical data and surgical tissue samples from 68 TNBC patients who underwent initial surgery were included in the analysis and 36 control samples from benign breast tissue biopsies., Results: A higher expression of TILs, CD4, CD8 and PD-L1 was found in the invasive tumor front (ITF), as compared to the tumor center (TC) (p < 0001). HSP70 positive immune cells (HSP70(+) IC) in TC were associated with adverse clinical and pathological markers: higher stage of disease (P = 0.013), higher grade (P = 0.05) and a higher pN status (P < 0.001). In addition, higher expression of HSP70(+) IC from TC was correlated with the higher expression of FOXP3(+)T cells both in ITF (N = 61, rho=0.42, p < 0.001) and in metastatic tissue from the draining lymph nodes (N = 13, rho=0.61, P = 0.026)., Conclusion: Correlations between HSP70 immune cells expression and individual TILs components support the hypothesis of its active role in inducing immunosuppression and tumor progression. Routine determination of HSP70 expression, in immune cells of TC, may be of added value in the clinical decision-making process concerning axillary surgery., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Purpose: To explore the relationship between histologic chorioamnionitis (HCA) and decidual macrophage (DM) polarization and their influence on outcomes of neonates born before the 32nd gestational week., Materials and Methods: Eighty-four neonates and their placentas were included in this retrospective case-control study and divided into two groups: with and without HCA present (HCA + and HCA-). Neonatal, maternal, and placental risk factors were explored and their influence on neonatal outcomes was examined. We used CD68 and iNOS as markers for polarized DMs type 1 (M1) and CD163, CD206 and arginase (Arg-1) for polarized DMs type 2 (M2)., Results: HCA was present in 47 (56%) cases, and 37 (44%) cases were without the present HCA. There was no statistically significant difference in neonatal risk factors between the two groups (HCA + and HCA-). Higher rates of HCA ( p  = .042) were observed in mothers who received antepartum corticosteroid therapy. The frequency of vaginal deliveries in HCA + pregnancies was significantly higher than in HCA- pregnancies where deliveries by cesarean section were more frequently observed ( p  < .001). M2 DM were more abundant in the HCA + group ( p  = .035). Multiple regression model assessed the association between the presence of HCA, M1, and M2 DM with ROP stages. It has been observed that HCA is a risk factor for ROP stages ( β coefficient = 0.34, r partial  = 0.246, p  = .024). With the logistic regression model, the association between the presence of HCA, M1, and M2 DM with neonatal nCPAP respiratory support and necrotizing enterocolitis (NEC) was assessed. The presence of M2 macrophages in decidua is an independent risk factor for neonatal nCPAP respiratory support (coefficient -0.07, OR = 0.928, 95% CI 0.87-0.99, p  = .024) and the presence of M1 macrophages in decidua increases the risk for NEC (coefficient 0.010, OR = 1.0108, 95% CI 1.00-1.02, p  = .032)., Conclusions: The significantly more abundant presence of M2 DM was detected in HCA + placentas and their association with the increased risk for neonatal nCPAP respiratory support was observed. On the contrary, the presence of M1 DM increases the risk for NEC. The presence of HCA is a risk factor for ROP stages.

Breast cancer is a heterogeneous disease with different biological outcome and ability to acquire resistance to therapy. The calpain family of proteases and androgen receptor (AR) are implicated in breast cancer pathogenesis and progression and are potential targets for novel treatment regimens. The aim of this study was to investigate the expression of calpain-1 and AR in breast cancer and to correlate their expression with clinicopathological variables and prognosis of patients. In this study we enrolled 219 breast cancer patients with long term follow-up information available. Immunohistochemical methods on a tissue microarray were used to investigate expression of calpain-1 and AR in tumor cells. The expression of calpain-1 and AR both differed significantly between the tumor subtypes of patients (p = 0.002 and p = 0.042 respectively). High calpain-1 expression was associated with patient's age over 50 years (p = 0.005) and positive ER status (p = 0.009), but not with other clinicopathological variables. Women with AR negative breast cancers were more likely to be older (p = 0.016), to have bigger tumors (p = 0.032), higher stage of the disease (p = 0.026), presence of exulceration (p = 0.017), negative ER status (p = 0.007) and higher Ki-67 proliferative index (p = 0.027). Calpain-1 expression was not associated with breast cancer specific overall survival in the total cohort of patients, however low calpain-1 expression was associated with adverse survival (p = 0.018) in triple negative subgroup of patients. Low calpain-1 expression was also associated with significantly shorter 5-year disease-free survival in total cohort of patients (p = 0.03). AR status was not associated with overall and disease-free survival of patients. This study has demonstrated that the expression of calpain-1 and androgen receptors are associated with important clinicopathological variables. The expression of calpain-1 was associated with improved disease-free survival of all analyzed patients and with improved overall survival of triple negative breast cancer patients., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Introduction : Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. The aim was to investigate paths of assumed causality leading from foetal inflammatory response syndrome (FIRS) to asthma symptoms in preterms. Methods : Demographic, antenatal, delivery and outcome data were collected from 262 infants with less than 32 completed weeks of gestational age over a 10-year period in a prospective cohort study. The presence of symptoms of asthma beyond the age of 5 years was the primary outcome measure. The causal effect of FIRS on childhood asthma was tested with three different logistic regression models and two structural equation models (SEM). Results : FIRS (OR = 4.7) and subsequent chronic lung disease of prematurity (OR = 7.7) and early childhood wheezing (OR = 9.5) are the most important risk factors for development of asthma symptoms in children born with less than 32 weeks of gestational age. The path analysis showed that FIRS has a large direct (0.59), medium indirect (0.11) and large overall (0.70) effect on CLD; large negative direct effect on ECW (-0.34) and a large positive indirect effect (0.74), mediated by CLD. On the occurrence of asthma symptoms, FIRS has a medium negative direct effect (-0.18) and a medium positive indirect effect (0.26), mediated by CLD and ECW. Conclusion : Prenatal inflammation plays an important role in the development of chronic respiratory disturbances in preterm infants. This influence is mainly related to structural and developmental lung abnormalities initiated in utero as consequences of FIRS, resulting in CLD of prematurity, and overcoming the protective mechanisms of chorioamnionitis.

Accurate assessment of HER-2 status is essential for identifying patients who will benefit from HER-2 targeted therapy. The aim of the present study was to show results on the concordance between local and central laboratory testing results in HER-2 positive breast cancer patients. In cases with discordant findings, the immunohistochemical (IHC) and/or in situ hybridization (FISH/SISH) analysis was performed in central laboratories. A total of 104 out of 143 (72.72%) breast carcinoma cases were HER-2 positive (score 3+), while nearly 14% of tumors (20/43) showed weak (score 2+) and 12% (19/143) negative IHC staining (score 0 and 1+). After repeated IHC and ISH, 88% (126/143) were classified as HER-2 positive and 12% (17/143) as HER-2 negative cases. The results obtained are in agreement with many studies that confirmed similar discordance in HER-2 testing by IHC and/or FISH between local and central laboratory. Thus, our findings as well as those from other studies support the importance of regular quality assessment of the staining procedures performed and consistency of interpretation of HER-2 test results.

Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia.

Background: Long-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children., Aims: We aimed to investigate the perinatal and maternal risk factors involved in the development of chronic respiratory morbidity in preterm infants, with an emphasis on the importance of Foetal Inflammatory Response Syndrome (FIRS)., Study Design: Prospective cohort study., Subjects: Demographic, antenatal, delivery and outcomes data were collected from 262 infants with less than 32 completed weeks of gestational age, over a 10-year period., Outcome Measures: Presence of chronic lung disease of prematurity and early childhood wheezing., Results: In multivariate logistic regression analysis the presence of FIRS appears to be the most important risk factor for both, chronic lung disease of prematurity (OR 31.05, 95% CI 10.7-87.75, p<0.001) and early childhood wheezing (OR 5.63, 95% CI 2.42-13.05, p=0.01). In the alternative regression model for early childhood wheezing, with chronic lung disease included as a variable, the statistical significance of FIRS completely vanished (OR 1.15, 95% CI 0.39-3.34, p=0.79), whilst chronic lung disease became the most important risk factor (OR 23.45, 95% CI 8.5-63.25, p<0.001)., Conclusions: Prenatal and early neonatal events are of utmost importance in the development of chronic respiratory symptoms in children. The influence of FIRS on the development of chronic respiratory symptoms goes far beyond its impact on gestational age and may be related to direct inflammation-mediated lung tissue damage. CLD appears to be an intermittent step on the way from FIRS to ECW., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Breast cancer shows extensive clinical and molecular heterogeneity. Prognostic factors are very important for outcome estimation in individual patients. Nuclear factor κB (NF-κB) and hypoxia-inducible factor 1α (HIF-1α) are transcriptional factors involved in cancerogenesis and in the metastatic spread of tumor cells. The aim of this study was to evaluate the expression of NF-κB and HIF-1α and to correlate the immunohistochemical expression of these markers with the breast cancer subtype and the patient outcome. The retrospective study included 208 cases of ductal invasive breast cancers stratified by the molecular subtype according to the St. Gallen 2011 classification. The Kaplan-Meier survival curve showed that an increased mortality risk was associated with tumors belonging not to the luminal A subtypes but to the Her-2-enriched and luminal B-Her-2-positive subtypes instead (P<0.001). Activation of NF-κB was associated with estrogen-negative tumors (P=0.005). We found a better overall survival in NF-κB-positive tumors in the luminal A subtype (P=0.021). This may be explained as a consequence of a possible tumor-suppressing effect of NF-κB. HIF-1α was related to the overall survival as a poor prognostic factor (P=0.036). In our opinion, the practical relevance of NF-κB and HIF-1α expression as prognostic indicators and potential targets for specific therapies deserve further investigation.

The aim of this study was to evaluate the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in prostate cancer in the main tumor mass and tumor cells at the positive margin as well as the influence of these biomarkers on the biochemical recurrence of the disease in prostatectomy patients. Tissue microarrays of 120 archival prostate carcinoma samples were immunohistochemically evaluated for MMP-2 and MMP-9 expression and compared with clinicopathological parameters. Tumors with positive surgical margins showed significantly higher overall expression of MMP-9 versus tumors with negative resection margins (P = 0.0121). MMP-9 expression was significantly elevated in tumors from patients who had biochemical recurrence (P = 0.0207). In the group of patients with negative margins, MMP-9 expression above the cut-off value was significantly associated with recurrence (P = 0.0065). Multivariate analysis indicated that MMP-9 is a good predictor of biochemical recurrence (odds ratio = 10.29; P = 0.0052). Expression of MMP-2 in tumor cells was significantly higher at the positive margins than in the main tumor mass (P = 0.0301). The present results highlight the potential value of MMP-2 and MMP-9 expression for predicting the behavior of prostate tumors after prostatectomy with both positive and negative surgical margins.

Sentinel lymph node (SLN) biopsy is an accurate method for the detection of axillary metastases in early breast cancer patients and is of value as a replacement for axillary dissection. However, variations in the methods and protocols used for the pathological evaluation of SLN exist in everyday practice. Therefore, standardization how to detect, dissect, process, stain, assess and report SNL is required in order to stratify patients into adequate prognostic groups. The aim of this study was to present our experience in SLN analysis in patients with early breast cancer and clinical stage T1-2 and N0. In the period between 2003 and 2011, 1071 consecutive patients or 1915 SLN were analyzed. The protocol included intraoperative analysis of histological frozen sections and cytological imprint, followed by analysis of paraffin sections according to the protocol that included sections of whole SLN with the interval of 250 prm. According to the accepted protocol 75% of SLN were negative. The obtained results were correlated with literature data.

Current evidence suggests that additional pathogenetic factors could play a role in the development of chronic lung disease of prematurity, other than mechanical ventilation and free radical injury. The introduction of the concept of "fetal inflammatory response syndrome" offers a new perspective on the pathogenesis of chronic lung disease of prematurity. New statistical approaches could be useful tools in evaluating causal relationships in the development of chronic morbidity in preterm infants. The aim of this study was to test a new statistical framework incorporating path analysis to evaluate causality between exposure to chorioamnionitis and fetal inflammatory response syndrome and the development of chronic lung disease of prematurity. We designed a prospective cohort study that included consecutively born premature infants less than 32 weeks of gestation whose placentas were collected for histological analysis. Histological chorioamnionitis, clinical data, and neonatal outcomes were related to chronic lung disease. Along with standard statistical methods, a path analysis was performed to test the relationship between histological chorioamnionitis, gestational age, mechanical ventilation, and development of chronic lung disease of prematurity. Among the newborns enrolled in the study, 69/189 (36%) had histological chorioamnionitis. Of those with histological chorioamnionitis, 28/69 (37%) were classified as having fetal inflammatory response syndrome, according to the presence of severe chorioamnionitis and funisitis. Histological chorioamnionitis was associated with a lower birth weight, shorter gestation, higher frequency of patent ductus arteriosus, greater use of surfactant, and higher frequency of chronic lung disease of prematurity. Severe chorioamnionitis and funisitis were significantly associated with lower birth weight, lower gestational age, lower Apgar score at 5 minutes, more frequent use of mechanical ventilatory support and surfactant, as well as higher frequency of patent ductus arteriosus and chronic lung disease. The results of the path analysis showed that fetal inflammatory response syndrome has a significant direct (0.66), indirect (0.11), and overall (0.77) effect on chronic lung disease. This study demonstrated a strong positive correlation between exposure of the fetus to a severe inflammatory response and the development of chronic lung disease of prematurity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer.

The "round block" surgical technique in the treatment of a female patient with multiple, multicentric fibroadenomas in both breasts is presented. The advantages of this technique for patients with multicentric benign breast lesions are minimal postoperative scar and a favourable aesthetic result. Breast dimensions and the areolar diameter were measured in 203 subjects of Primorsko-Goranska county during examination in the Out-Patient Hospital for Breast Diseases, including the operated patient. Smaller breast dimensions and a larger areolar diameter provide an easier access to any part of the breast due to a smaller distance between the incision and a fibroadenoma and a larger circumference of circular periareolar incision, thus facilitating the surgery. The analysis of average, maximum and minimum values measured shows that the "round block" technique can be performed in all cases of multiple and multicentric fibroadenomas regardless of breast size, areolar diameter and the location of fibroadenoma in the breast.

The epidermal growth factor receptor (EGFR)-family and cyclin-D1 have been extensively studied in breast cancer; however systematic studies that examine protein expression and gene status in the same cohort of patients are lacking. Also emerging evidences suggest existence of a direct EGFR-signaling pathway, which involves cellular transport of EGFR from cell membrane to the nucleus, and transcriptional regulation of the target genes. Thus, we examined the protein expression of membrane EGFR, nuclear EGFR, cyclin-D1 and the corresponding gene status in 113 breast carcinomas by immunohistochemistry and fluorescence in situ hybridization using tissue microarrays. Membrane EGFR overexpression and EGFR gene amplification were detected in 2% cases, while nuclear EGFR was detected in 40% of cases, with 12% having high nuclear EGFR staining. Nuclear EGFR correlated with tumor size (P=0.0005), lymph node metastasis (P=0.0288), Nottingham prognostic index (P=0.0011) and estrogen receptor (ER) expression (P=0.0258) but the letter correlation was observed only in premenopausal group of patients. Strong cyclin-D1 expression and cyclin-D1 gene (CCND1) amplification were found in 64 and 13% of the cases, respectively. Cyclin-D1 expression showed positive correlation with ER (P=0.0113) and inverse correlation with Nottingham prognostic index (P=0.0309) and membrane EGFR (P=0.0201). CCND1 amplification also showed inverse correlation with membrane EGFR (P=0.0420). A strong correlation between membrane EGFR expression and gene amplification (P=0.0035), as well as cyclin-D1 overexpression and gene amplification (P=0.0362), was demonstrated. On univariate analysis cyclin-D1 expression showed a correlation with longer overall survival in the premenopausal group and nuclear EGFR correlated with shorter overall survival in whole cohort as well in the premenopausal group of patients. Multivariate analysis revealed nuclear EGFR to be an independent prognostic factor and showed 3.4 times greater mortality risk for nuclear EGFR+++ patients as compared with nuclear EGFR negative patients (hazard ratio =3.402; P=0.0026).

Axillary lymph node dissection (ALND) is an important procedure in the staging of breast cancer patients. However, it is associated with a significant morbidity rate. In addition, using early diagnosis a high number of cases with negative lymph nodes can be identified. A lymph node defined as sentinel lymph node (SLN) would be the first to receive tumoral drainage. A less morbid but accurate staining procedure using mapping and SLN biopsy has been introduced. The aim of this study was to estimate the likelihood of additional disease in the axilla after SLN analysis. A total of 259 breast carcinomas and SLN biopsies followed by ALND were examined. The patient median age was 59 years, approximately 75% of them postmenopausal. Tumor size was 1.4 +/- 0.8 cm (almost 80% in pT1). SLNs were positive in 59 of 259 (22.8%) carcinomas, 30 (11.6%) with micrometastases (<2.0 mm) and 29 (11.2%) with metastases. Tumor size ( P = .004) and presence of lymphovascular invasion (LVI; P = .034) were found to be significant predictors of pathologically positive SLN. Following ALND, positive non-SLNs were present mostly in patients with metastasis >2 mm in SLN (P = .003), in carcinoma with higher nuclear grade ( P = .044), decreased estrogen receptor (ER; P = .042), and progesterone receptor (PR; P = .042). Finally, lymph node status (pN) following SLN and ALND was found to be significantly associated with tumor size ( P = .006), LVI (P = .037), PR (P = .023), and Her-2 status (P < .001). These results point to detailed analysis of primary tumor and SLN that may increase the precision of patient selection for further axillary surgery or radiotherapy.

The aim of this study was to analyse breast carcinomas with discordant receptor status, probably hormonal dependent (estrogen receptor (ER) positive, progesterone receptor (PR) negative or ER-PR + subgroup profile) infiltrating ductal breast carcinomas not otherwise specified (IDC NOS). Specimens from 90 IDC NOS were grouped into three categories according to hormonal status: dependent (D) (ER +PR +), probably dependent (PD) (ER +PR- or ER-PR +) and non-dependent (ND) (ER-PR-); they were evaluated considering some established prognostic parameters in breast carcinomas. Statistically significant difference was found between tumor receptor status distribution and menopausal status (p = 0.0235), age of the patients (p = 0.000467), histological grade (p = 0.000003), vascular invasion (p = 0.006), HER-2 status (p = 0.0039) and Ki-67 proliferation rate (p = 0.000311). D tumors were found exclusively in post-menopausal patients (average age 68.9 years), most of which had intermediate (II) grade, without vascular invasion, with HER-2 status score predominantly 0 or 1 + and lower Ki-67 proliferation rate. PD tumors were found predominantly in younger post-menopausal patients (average age 57.5 years), with vascular invasion found in 23% of the cases. ND tumors mostly had higher histological grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases. We conclude that the patients with PD breast carcinomas were younger post-menopausal women with the tumors moderately differentiated, HER-2 score 0 or 1+ and with lower Ki-67 proliferation rate.

This communication presents the first case of complete trisomy 19q, prenatally detected by ultrasound investigation. Real-time high-resolution ultrasound examination was performed at 19 weeks of gestation. After termination of the pregnancy, autopsy investigation was done. GTG-banding, fluorescence in situ hybridization m-(FISH) analysis, and FISH analysis with a 19q subtelomeric specific probe were used for identification of the fetal karyotype. Sonographic examination revealed an enlarged cisterna magna, cerebellar hypoplasia and aplasia of the inferior part of the vermis, combined and bilateral kidney malformations, significant nuchal fold, absence of fetal nasal bones, and intracardial calcifications. Autopsy confirmed ultrasound findings, but also revealed situs viscerum inversus of the lungs. Fetal karyotype was defined as: 46,XY,der(21)t(19;21)(q11;p13)mat. Our ultrasound and autopsy findings will certainly contribute to better knowledge of phenotype characterization of this rare chromosomal disorder.

The aim of this study was to analyze the association between vascular endothelial growth factor (VEGF) expression on tumor cells and other clinicopathologic parameters in breast cancer that could give additional information on its prognostic significance. Immunohistochemical analysis of expression of VEGF, estrogen (ER) and progesterone receptor (PR), HER-2/neu, and Ki67 was performed in 233 breast cancers. VEGF expression estimated semiquantitatively was correlated with all the above-mentioned parameters as well as with clinicopathologic characteristics of breast cancer such as menopausal status of patients, tumor size, histologic and nuclear grade, vascular invasion, and lymph node status. Most of the tumor cells and some stromal components expressed VEGF. A higher percentage of VEGF-positive tumor cells was present in premenopausal patients and in ER-negative tumors. In postmenopausal patients tumors with a higher expression of VEGF were associated not only with ER-negative but also with HER-2/neu-positive tumor cells. These ER-negative tumors were characterized by a higher proliferative activity. Angiogenic switch as well as proliferative activity of breast cancer cells probably are unfavorably dependent on estrogen activity. This negative correlation between VEGF expression and ER status may not only shed more light on tumor biology but may also have future therapeutic implications., (Int J Surg Pathol 14(1):49-55, 2006.)

Aim: To analyze the expression of bone morphogenetic proteins (BMPs) in prostate and breast cancers with established metastasis in bone, where prostate cancer causes osteoblastic metastases, and breast cancer osteolytic metastases., Methods: Primary tumor specimens from 20 patients with prostate cancer and 15 with breast cancer were studied for BMP-2/4, -3, -5, -6 and -7 immunohistochemistry. All patients had multiple bone metastases proven by bone scan. We also examined BMPs expression in normal prostate and breast tissues. BMPs expression was compared with clinicopathological and biochemical parameters., Results: Cytoplasmic BMPs immunostaining was observed in both prostate cancer and normal prostate tissue. Expression of BMP-2/4, -5, -6, and -7 proteins was detected in all normal prostate samples, with the predominance of BMP-2/4 (87.8-/+11.4% positive cells) and BMP-7 (94.6-/+0.9% positive cells). In prostate cancer tissues, we found variable expression of all BMPs. BMP-2/4 (83-/+11.6% positive cells) was predominantly expressed in prostate carcinoma, whereas the expression of BMP-7 (24.3-/+19.2% positive cells) was significantly lower than in the normal prostate. In all breast cancers tissues, we found nuclear staining only for BMP-7. In normal breast tissue, the BMP expression was not detectable. The percent of BMP-7 positive cells in breast cancer (86.4-/+7.3%) was higher than in prostatic cancer. Comparing BMP expression levels and clinicopathological parameters, we did not find statistical difference, except for serum alkaline phosphatase, which was significantly higher in patients with prostate cancer., Conclusion: The expression of BMPs differs between prostate and breast cancer cells. Identifying the BMP proteins in cancers may be useful for monitoring the tumor status with reference to metastases.

Urinary bladder cancers can be grouped into three general categories: superficial, invasive and metastatic. Approximately 90% of malignant tumors of the urinary bladder are of epithelial origin and the majority of them are transitional cell carcinomas (TCC). Metastatic spread of urinary bladder cancers usually includes regional lymph nodes, the lung, the liver and the bones. The presence of metastasis tends to correlate with muscular wall invasion as often demonstrated at the initial diagnosis; consequently clinical bladder cancer represents a late phase of the disease. Although skeletal metastases of bladder cancers are rather common, they have been rarely described to occur in distal bones. For that reason, we report metatarsal metastasis from transitional cell cancer of the urinary bladder in a 59-year-old woman.

Neovascularization, the growth and formation of capillary blood vessels, is an essential component of solid tumor growth and a critical step in metastasis. Tumor associated macrophages (TAMs) have several functions related to tumor biology including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define the TAM and microvessel density (MD) in human invasive breast carcinoma NOS and to correlate their values with lymph node status, tumor size, tumor grade and mitotic activity index (MAI), and, finally, to determine whether MD is connected with TAMs. A total number of 57 invasive breast carcinomas NOS were processed for immunohistochemical analysis using mAb to F-VIII to visualize endothelial cells and mAb to CD68 antigens for macrophages. Statistical analysis showed only a positive correlation between TAMs and MAI (p = 0.004). These results support the notion that intensity of tumor angiogenesis does not provide additional prognostic significance, while TAMs may play a positive role in breast cancer micro system since they regulate tumor proliferation.

Histologic and nuclear grading (NG) have been widely used to predict the prognosis in patients with advanced breast cancer. However, NG has been criticized as a non-standard (several grading schemes used) and subjective (significant interobserver variability) method for predicting the biologic behavior of this tumor. Our results on 106 invasive ductal breast carcinomas demonstrate that NG correlates with morphometric prognostic index (MPI) (p < 0.007) (lower value of MPI is connected with lower NG of 1-2 and better prognosis), with estrogen receptor (p < 0.0002) and progesteron receptor status (p < 0.04) (hormonal receptor positive tumors having lower NG). NG correlates with s-phase fraction (SPF), p < 0.04, values lower than 9.6% corresponding to lower NG. We consider NG to give important information about the biologic behavior of the tumors under observation, demonstrating a good correlation with more established parameters such as MPI and SPF.

The integrins are transmembrane alfabeta heterodimers mediating cell-cell as well as cell-extracellular matrix interactions. The present study was designed to analyse the expression of beta-1 integrins on cryostat sections of invasive ductal carcinomas not otherwise specified by avidin-biotin complex immunoperoxidase technique, and to compare it with the morphometric prognostic index (MPI). The results show that the expression of beta-1 integrins is heterogeneous in the tumors. This heterogeneity was observed in quantitative and qualitative staining pattern. There was an absent expression of beta-1 integrins in 22 out of 55 tumors while 33 showed staining, weak on 23 cases and strong on 10 infiltrative ductal carcinomas. Statistical analysis pointed to some correlation of beta-1 integrins with some morphometric parameters. Low or absent expression of beta-1 integrins correlated significantly with tumors exceeding 2 cm (p < 0.0245). Moreover, a larger proportion of tumors with positive lymph nodes showed absence of beta-1 expression compared with negative lymph node, and this was also statistically significant (p < 0.0076). Correlation between mitotic activity index and staining intensity for beta-1 integrins was not found (p < 0.372). When tumors with different beta-1 expression were subdivided according to MPI values into two groups, one group with a low-risk, < 0.6, and second with a high risk, > 0.6, concordance in prognostic value was shown between MPI and beta-1 expression (p < 0.0193). These results support the idea that loss of beta-1 integrins correlates with the invasive and metastatic potential of tumor cells.