Corelation of lymphocytic infiltrates with the prognosis of recurrent colo-rectal cancer.

BACKGROUND: Recent studies are focusing on complementary prognostic and predictive markers that could complete the predictive TNM staging and one of the most promising directions is the study of tumor immune infiltrates. MATERIALS AND METHODS: Our 2-year retrospective study includes resection specimens from the primary tumors of 23 patients presenting to our clinic for a local or a distant relapse after colon or rectal cancer. From every primary tumor specimen we obtained immunohistochemically stained slides in order to assess cd3, cd4, cd8, cd45ro and cd68 infiltrates. Digital analysis assessed the density and percentage of positively stained cells in the normal peritumoral tissue, invasive margin and center of the tumor. RESULTS: A small density of cd8 positive cells in the peritumoral region was strongly correlated with a longer disease-free interval (p=0.009) and the Kaplan-Meier survival analysis showed that the percentage of cd8+ T cells could be used to stratify patients in terms of relapse risk (p=0.006). We found no correlation between invasion front infiltrates and intra tumoral infiltrates and the disease-free interval. CONCLUSION: Our study concludes that cytotoxic T-cell infiltrates in the normal peritumoral tissue could be used to predict a more aggressive tumor in terms of the relapse risk.

Laser microdissection--a novel approach for accessing the molecular basis of cancer.

BACKGROUND AND AIM: It has been known for quite a lot of time that tumours are cellular aggregates of different cells, mainly malignant cells but also immune cells--of which the most well-known are the tumour infiltrating lymphocytes (TIL) and the tumour associated macrophages (TAM). By observing hematoxylin--eosin stained or immunohistochemical stained slides belonging to different areas of the tumour it is clear that there are clusters of malignant cells within the tumour itself that seem to behave differently from the rest of the tumour. Another fact is that different areas of the tumour contain different inflammatory cells which may promote carcinogenesis or may help to confine it. Whereas different immune cells can be recognised by using immunohistochemistry, a satisfactory characterization of the molecular characteristics of the malignant clusters of the tumour cannot be made without further use of different molecular techniques such as different PCR techniques or microarray methods. Laser microdissection thus comes as a valuable aid in choosing exactly which cells will be analyzed further on. PRINCIPLE OF THE METHOD: Laser microdissection is based on using the energy of a focused laser beam to cut through the thickness of the tissue that is placed on a microscope slide in order to obtain cell samples previously selected by the pathologist through special software. CONCLUSIONS: To be able to cut the cells that you want and analyze them further without having them contaminated with other cells means that you can get more insight into the progression of the mutations that occur in these malignant cells, mutations that cause them to become more aggressive or multidrug-resistant. This could in time lead to the discovery of new molecular targets for cancer therapy.

Optimization of culture conditions for bone marrow stromal cells in RPMI-1640 medium.

UNLABELLED: Bone marrow mesenchymal stem cells are important for both research and clinical purpose. A number of culture methods for these cells are available on the market, many of them consisting of specialized growing media in combination with growth factors. Our goal was to optimize a less expensive culture method for bone marrow mesenchymal cells. MATERIAL AND METHODS: Eight samples of bone marrow aspirates from patients were used. Out these 8 samples 2 were from healthy people, 3 from chronic granulocytic leukemia patients, 2 from multiple myeloma patients and 2 from patients with myelodysplastic syndrome. Bone aspirates from healthy people were used to optimize the culture method and the rest were used for testing the optimized method. Two methods were tried: 1. Cell culture starting from whole bone marrow, 2) cell culture after bone marrow separation in density gradient with Histopaque. RESULTS: Cell culture starting from whole bone marrow gives better yields for mesenchymal stem cells than methods which include gradient density separation of mononuclear cells with Ficoll-Histopaque. CONCLUSIONS: We have optimised a less expensive cell culture method for bone marrow mesenchymal cells.

Thapsigargin-induced endoplasmic reticulum stress is not accompanied by mitochondrial membrane potential dissipation in murine pro-B cells.

UNLABELLED: There are almost no data concerning the involvement of endoplasmic reticulum stress (Ca2+ fluxes) in the apoptosis of the pro-B cell type Ba/F3. Thus, we aimed the characterization of thapsigargin-induced effects on Ba/F3 cells in vitro. MATERIAL AND METHOD: For some experiments Ba/F3 cells were treated with 1 microM thapsigargin for 24 hours. To compare, we used as positive control the effects of valinomycin 10 microM. The negative control Ba/F3 cells received no treatment for 24 hours. After that, all batches of Ba/F3 cells were incubated in the presence of 1 mimcroM JC-1 (Sigma-Aldrich) at 37 degrees C for 30 minutes. RESULTS: From the normal Ba/F3 JC-1-control cells (20.000 events gated by flow cytometry) 77.61 +/- 2.90% are associating high and 22.39 = 2.90% lower mitochondrial membrane potential. In the case of thapsigargin, 75.49 +/- 1.78% of the Ba/F3 cells are associating high and 24.51 +/- 1.78% lower mitochondrial membrane potential. CONCLUSIONS: While mitochondrial permeability transition pore (MPTP) opening necessarily correlates with a loss of mitochondrial membrane potential (Psi(mt)), a decrease in Psi(mt) does not necessarily indicate MPTP opening. Also, endoplasmic reticulum stress regulation of high cytosolic calcium levels by thapsigargin may prompt the opening of the MPTP without necessarily triggering irreversible pore activation or subsequent apoptogenic factors in Ba/F3 cells.

Neoangiogenesis in cervical cancer: focus on CD34 assessment.

UNLABELLED: Despite recent advances in understanding the immune mechanisms of cervical cancer (CC), relapse remains still an actual issue and recognition of new predictive biomarkers is essential. AIM: The purpose of this retrospective study was to investigate neo-angiogenesis in CC and its possible utility as prognostic biomarker. MATERIAL AND METHODS: Paraffin-embedded tissue samples from 61 consecutive women with CC were immunostained for CD34 and E-cadherin. Statistical analysis was performed in SPSS-12 software, p<0.05. RESULTS: Statistically significant differences between CD34 distribution among three interest tumor regions: micro-vessels density increase from central to peripheral area (chi(2), p<0.05); statistically significant correlation between CD34 expression, particularly in stromal and peripheral sites, E-cadherin (Spearman r1=-0.321) and lymphatic invasion (Spearman r2=0.455) (p<0.05) were reported. Overall five-year survival is clearly dependent on level and distribution of tumor angiogenesis among defined area of interest as suggested by Kaplan-Meier analysis. CONCLUSIONS: Angiogenesis is essential for guiding CC evolution and prognosis, particularly in squamous invasive types.

Immunohistochemical study of colorectal cancer liver metastases: the immune/inflammatory infiltrate.

Our study is focused on the investigation of the immune/inflammatory infiltrate in liver metastases secondary to colorectal cancer. Twenty cases of colorectal liver metastases have been studied, including eight with recurrent metastases occurred after a previous treatment by thermonecrosis (group 1) and 12 with primary metastases treated exclusively by surgery (group 2). The cases were investigated by routine histopathological exam and by immunohistochemistry, using CD3, CD20 and CD68 antibodies. The design of the study envisages a comparative qualitative and quantitative evaluation of the B- and T-lymphocytes and macrophages inside the tumor and at the interface between liver parenchyma and tumor. Student's t-test was used for all statistical comparisons. The qualitative exam revealed, for both groups, the presence of an important T-lymphocyte, and respectively B-lymphocyte cell population at the interface between the tumor and the liver parenchyma, the number of intratumoral cells being extremely reduced. The statistical analysis showed significant differences (p<0.05 for groups 1 and 2, T- and B-lymphocytes, intratumoral vs. peritumoral). However, the comparison of group 1 with group 2 revealed no statistically significant differences between the mean value of intratumoral and peritumoral T- and B-lymphocytes, respectively. The qualitative exam revealed the presence of a well represented macrophage cell population, with a heterogenous distribution from case to case. This finding was confirmed by numerical information, with a lack of a statistically significant difference between the mean number of macrophages quantified intra and peritumoral, for both study groups. However, statistically significant differences were noticed between intratumoral and peritumoral mean value, respectively, for group 1 vs. group 2 (p<0.05). T-lymphocytes are the most numerous, their peritumoral location being the landmark for the histoarchitecture of the immune/inflammatory infiltrate and conducting the immune response developed at the interface between the tumor and liver parenchyma. The quantitative assessment of the immune infiltrate shows similar features in surgically resected metastases and recurrent metastatic disease after thermonecrosis. On the contrary, the quantitative evaluation of the macrophage population indicates a functional association rather with the primary metastasis process than with the recurrent metastatic disorder.

Predictive value of cellular immune response in cervical cancer.

UNLABELLED: Despite recent advances in the immune mechanisms of cervical cancer (CC), the relapse still remains an actual issue and recognition of new predictive biomarkers is essential. AIM: The purpose of this retrospective study was to investigate possible differences in the primary, in situ, cellular immune response between cervical carcinoma with and without relapse. MATERIAL AND METHODS: Paraffin-embedded tissue samples from 61 consecutive women with CC (34 with and 27 without relapse) were immunostained for CD3, CD20 and CD45 cells. Immune cell profile densities were further assessed, assigning scores between 0 and 3: "0" meaning the absence of inflammatory infiltrate, "1+" low, "2+" intense and "3+" intense infiltrate with lymphoid follicles. Statistical analysis was performed in SPSS-13 software, p<0.05. RESULTS: Statistically significant intra- and peri-tumoral low numbers of several immune cell subtypes are strongly associated with relapse of disease within three and five years in patients with CC (p<0.05); moreover, statistical significant correlations between immune cells and both free survival (CD3: r=0.382; CD20: r=0.404; CD45: r=0.376) and relapse (CD3: r=-0.408; CD20: r=-0.355; CD45: r=-0.354) have been demonstrated. Only CD3 was reported as predictive biomarker of relapse in CC (ANOVA, t-Student, p<0.05). CONCLUSIONS: Major differences in the cellular immune response among patients with cervical cancer with and without relapse within three and five years have been demonstrated. CD3 may be used as potential prognostic biomarkers, whereas the results are promising for adjuvant immunotherapy.

Tumor biomarkers in cervical cancer: focus on Ki-67 proliferation factor and E-cadherin expression.

UNLABELLED: Despite recent advances in the immune mechanisms of cervical cancer (CC) and complex management opportunities, relapse remains still an actual issue. While predictive factors are required, current research is directed towards proliferation and tumor aggressiveness biomarkers as potential negative factors in CC. The main objectives were to assess tumor proliferation and invasiveness biomarkers (Ki-67, E-cadherin) and to identify potential correlation between biomarkers and classic prognostic factors in CC. Radical hysterectomy specimens from 61 consecutive CC were immunohistochemically investigated for Ki-67 and E-cadherin. Nuclear immunostaining for Ki-67 proliferation index was assigned scores 1 to 3, "+" meaning low (10-30%), "++" moderate (30-50%), "+++" high-proliferation rate (>50%); cell membrane E-cadherin staining was either negative or positive. Statistical analysis was performed in SPSS-13 software, p<0.05. RESULTS: no significant correlation between Ki-67 and classical prognostic factors (p>0.05) was reported; however, in relapsed CC, Ki-67 correlates with tumor grading (r=0.386, p<0.05). Significant correlation between E-cadherin and tumor size (r=-0.280, p=0.029), relapse (r=-0.386, p=0.002) and disease free survival (r=0.374, p=0.003) were demonstrated. Indirect statistically significant moderate correlation between Ki-67 and E-cadherin (r=-0.461, p<0.00001) was shown, mainly in invasive squamous CC (r=-0.549, p=0.0001), stage IB (r=-0.578, p=0.009), IIB (r=-0.585, p=0.003), relapsed CC (r=-0.525, p<0.01), HPV-infection (r=-0.504, p=0.033). CONCLUSIONS: CC aggressiveness, particularly in invasive squamous carcinoma, either 16 or 18 HPV-positive cases, FIGO stage IB and IIB, and cases with relapse, depends on two pivotal factors, tumor proliferation rate (Ki-67) and tumor invasiveness (E-cadherin).

[Expression of Ki-67 in bronchial asthma]. / Nivelul expresiei factorului de proliferare Ki-67 in astmul bronsic.

UNLABELLED: In this paper we want to study the changes in the expression of cell proliferation factor Ki67 in the respiratory epithelium of patients diagnosed with bronchial asthma. MATERIAL AND METHODS: Twenty one patients with bronchial asthma having different degrees of severity (according to GINA 2002) have been included in our study. Fragments of bronchial mucosa were obtained through fiberbronchoscopy, prepared for histologic examination in view of immune marking with anti-Ki67 antibodies. RESULTS: Microscopic examination revealed a progressive increase in the number of Ki-67 cells in the respiratory epithelium corresponding to the severity of asthma (following FEV1 parameters). CONCLUSION: The increase in the cell proliferation in the respiratory epithelium represents one of the mechanisms that can help in rebuilding the epithelial structure destroyed by the chronic irritation.

Using MLPA for large genomic rearrangements detection in breast cancer predisposition genes.

UNLABELLED: Breast and ovarian cancer are common pathologies in women, with increasing incidences worldwide. In hereditary breast and ovarian cancer (HBOC) families, a large percentage of cases are attributable to hereditary factors compatibles with dominant autosomal transmission of a major tumour suppressor gene with incomplete penetrance. Screening for BRCA1 mutations is now standard practice for HBOC cases in western world, and permits medical follow-up and genetic counselling. Over 300 BRCA1 germinal mutations are stored in the Breast Cancer Information Core (BIC) mutation database. MATERIAL AND METHODS: Estimates in different countries range from 5 to 15% the BRCA1 related cases of hereditary breast cancer due to copy number changes of one or more exons of this gene. Exon deletions and amplifications will usually not be detected by sequence analysis of the complete BRCA1 gene, therefore MLPA screening is needed. RESULTS: Here we describe Multiplex Ligation-dependent Probe Amplification technique (MLPA) implementation for BRCA1 large genomic rearrangements. CONCLUSIONS: We did not detect any BRCA1 mutation by analysis of 15 HBOC recruited patients.

[Prognostic significance of leukemia-associated phenotype in correlation with other biologic markers in acute myeloid leukemia patients]. / Identificarea semnificatiei prognostice a fenotipului asociat leucemiei in corelatie cu alti markeri biologici la pacientii cu leucemie acuta mieloblastica.

UNLABELLED: Leukemic cells have unique aberrant phenotypes, which permit identification of this cells at diagnose and in evolution of the disease. Signaling molecules with other cells and bone marrow stroma are part of the leukemic cells phenotype. Genetic and molecular abnormalities have the main prognostic significance and confer the leukemic cell status. The main aim of the current study is to identify correlation between recognized prognostic factors in acute myeloid leukemia (AML) patients and other phenotypic markers. MATERIAL AND METHOD: Imunophenotypic analysis (BDFACS CantoII, FACSDiva Software) was performed on peripheral blood/bone marrow aspirate samples of 56 patients diagnosed with AML (9 M0, 3 M1, 10 M2, 4 M3, 28 M4/M5, 1 M6, 1 M7) between 2007-2009 in Hematology Department of "Sf. Spiridon" Hospital Iasi. We used an extended panel of monoclonal antibodies and we determined the level of expression of cytokines receptors (IL3Ra, IL7R) and chemokines (CXCR4, CKR5). RESULTS: In our study, IL7R expression on AML blasts was significant correlate with low WBC count at diagnosis (p = 0.04) and with multilinear displasia (p = 0.01), high CXCR4 expression was correlate (p = 0.05) with lack of response at first induction therapy and CD123 (IL3Ra) expression was correlate with M4 FAB phenotype. Survival was negative influenced by presence of IL3R on AML blasts, but flt3 mutations, CXCR4, IL7R expression on leukemic cells, other phenotypic aberrancies did not influenced treatment response and survival in our patients population. CONCLUSION: Complete investigation of leukemic cells phenotype extended with cytokines/chemokines receptors at diagnostic is useful for correct characterization of the disease, for discover new prognostic categories and for better identification of minimal residual disease.

[Specifics of individual risks in a group of women with genital neoplasms]. / Particularitati privind riscurile individuale la un lot de femei cu neoplazii genitale.

UNLABELLED: Genital cancers represent an important issue regarding women health, as they produce a large number of cases, invalidities and deaths. AIM: The evaluation of individual risks for a group of women with genital neoplasia. MATERIAL AND METHODS: We conducted a pilot case-control study to validate the questionnaire for the evaluation of risk factors in genital cancers, in a number of 40 female subjects (20 cases and 20 controls). We have realized the data processing using the SPSS 16 and EpiInfo 3.5.1. soft wares. RESULTS: For questionnaire validation we have evaluated the reproducibility, the validity, the acceptability and the practicability of the questionnaire. In order to establish the test reproducibility, we have calculated k factors for inter-investigator (k = 0.34) and intra-investigator (k = 0.72) variation. To evaluate the questionnaire validity we calculated the sensitivity (cases = 94%; controls = 97%), specificity (cases = 67%, controls = 75%), positive predictive value (cases = 94%; controls = 94%), negative predictive value (cases = 67%; controls = 86%). The risk factors most frequently identified were genital infectious in clinical records (75% comparing to 52.5% - p = 0.036), and also the presence of other pathological records in genital area (65% comparing to 22.5% - p = 0.0001). CONCLUSIONS: For an accurate identification of individual risk at women with genital cancers subsequently studies on greater number of subjects is necessary.

[Structural changes of tumor microenvironment in liver metastases of colorectal carcinoma]. / Modificari structurale de micromediu tumoral în metastazele hepatice ale carcinomului colorectal.

UNLABELLED: The immunohistochemistry represents a very effective tool for describing the biological phenomena that characterize the primary or secondary neoplastic development. By using a complex immuno-morphologic approach, our study aims to develop a characterization of the metastatic liver microenvironment, based on the following features: similarities and differences in the proliferation activity, particular aspects of vascularity and immune response, the cellular dialogue generated at the level of the parenchyma - neoplastic tissue interface, the structure of the associated stroma. MATERIAL AND METHODS: Ten cases of liver metastases have been studied, including five treated exclusively by surgery (group 1) and five with recurrent metastases occurred after a previous treatment by thermonecrosis (group 2). The cases were investigated by routine histopathological exam and by immunohistochemistry. The choice of the antibodies was motivated by the follow-up of the parameter classes presented below: (i) proliferation/apoptosis; (ii) structure; (iii) angiogenesis and lymphangiogenesis; (iv) immunological reactivity; (v) cytokines. RESULTS: The elements defining the histopathologic and immunohistochemical patterns allowed a comparative evaluation of the metastasis models considered for the two groups of studied cases. The analysis of proliferation / apoptosis parameters proved a high aggressiveness in tumor proliferation for both types of metastases. Recurrent metastases showed an increased angiogenesis and a moderate lymphangiogenesis, as well as a massive matrix reshaping. The evaluation of the inflammatory infiltrate suggested that the development of the liver metastases is not accompanied by significant immunologic rejection, but it rather induces the tissue remodeling at the invasion border level. The recurrence corresponds to a typical interval of 6 months or longer, and is associated with intense fibrogenesis, angiogenesis, and inconsistent inflammatory infiltrate. CONCLUSIONS: Therefore, the efficiency of the thermonecrosis procedure with water vapors seems to drastically depend on the complete necrosis of the target tumor, plus the adjacent cells of the parenchyma in a neighborhood of some millimeters. Moreover, the therapy must include anti-angiogenic resources as well as inflammation modulators, since the vascular supply and the leukocytic activity support the metastasis development.

[The management of unexplained recurrent abortions. Is immunotherapy an option?]. / Managementul avorturilor recurente de cauza neprecizata. Este imunoterapia o optiune?

Recurrent abortions, defined as more than three consecutive pregnancy losses, are associated with genetic, anatomic and endocrine causes. Whenever investigations fail to detect a cause, immunological dysfunctions are incriminated. The paper shortly reviews the main causes, investigation protocols and immune therapeutic attempts that have been made. Active immunization with allogenic leukocytes or trophoblastic membranes, passive immunization with intravenous immunoglobulins and immunomodulation with glucocorticoids in unexplained recurrent abortions generated contradictory results and was banned by reproductive immunology scientists as empirical, risky for the mother and harmful for the fetus. Confronted with desperate couples, clinicians use the immunotherapy with paternal lymphocytes or intravenous immunoglobulins in healthy women with unexplained recurrent abortions or in cases where accepted therapies failed.

Adipokines involvement in lung function.

The last two decades brings many data about white adipose tissue capacity to secrete hormones, named adipokines, which could mediate the relationship between obesity and lung diseases. In this paper we presented some data about adipokines involvement on pulmonary function, with special emphasis on leptin, adiponectin, tumor necrosis factor alpha, vascular endothelial growth factor, resistin, hepatocyte growth factor, interleukin-6, angiotensinogen and apelin.

Th1 and Th2 cytokine response in patients with pulmonary tuberculosis and health care workers occupationally exposed to M. tuberculosis.

UNLABELLED: Aiming to detect reliable markers indicating protection from or susceptibility to tuberculosis infection, we investigated both Th1/Th2 cytokines and total IgE plasma levels in health care workers occupationally exposed to M. tuberculosis, in patients with pulmonary tuberculosis and in healthy persons. MATERIAL AND METHOD: The study groups have included 15 health care workers in close contact with TB patients, patients with active pulmonary tuberculosis at diagnosis and after treatment (12 advanced and 10 moderate TB, of which 6 had also pleurisy) and 20 healthy volunteers. Peripheral blood mononuclear cells (PBMC) were stimulated with PPD for 7 days and the release of six cytokines (IL-2, IFN-gamma, TNFalpha, IL-4, IL-5, IL-10) was simultaneously quantified by cytometric bead array (CBA) in culture supernatants. The same method was used to determine the cytokine level in plasma and pleural effusions from TB patients. Six neoplastic pleurisies were included in this investigation as a control group. Total plasma IgE level was measured by chemiluminescence technique. RESULTS: Plasma and pleural fluid cytokine analysis at the outset of tuberculosis disease reflect the same Th1 response dominated by IFN-gamma. In opposition, very low IFN-gamma levels were recorded in neoplastic pleural fluids. Both types of cytokines (Th1 and Th2) were secreted in response to in vitro PPD stimulation of PBMCs and had different evolution in moderate and advanced TB. Thus, IFN-gamma, TNFalpha, IL-4, and IL5 production after 6 months-treatment decreased in moderate TB and increased in severe disease (p < 0.05). Moreover, total IgE plasma levels were higher than the normal value (87 IU/ml) in health care workers and significant amounts were recorded in patients, especially in advanced TB after 6 months of treatment (p = 0.00). CONCLUSIONS: Our results confirm that the quantification of IFNa could be a good marker for the diagnosis of TB pleural effusions but raised the question whether plasma IgE levels might be a reliable marker indicating the transition to disease. Further studies are needed to understand the complex interaction between pro- and anti-inflammatory cytokines that might play an Key words: TUBERCULOSIS, CYTOKINES,

T cell cytokine patterns in active tuberculosis patients in a northeastern area of Romania.

Developing countries like Romania have a high incidence of tuberculosis. Literature data suggest that people in these countries have an important Th2-type immune background which prevents a protective Th1 response of the host against Mycobacterium tuberculosis. Our study is the first attempt in Romania to identify cytokine patterns in active tuberculosis. The study included 15 patients with active pulmonary tuberculosis and 11 healthy volunteers. Peripheral blood mononuclear cells (PBMC), stained with carboxyfluoresceine-diacetate-succinimidylester (CFSE), were incubated for 7 days with purified protein derivate (PPD) or with medium alone. Intracellular synthesis of IFNgamma and IL-4 in proliferated (CFSE(low)) T cells was detected by flowcytometry. The results showed that both Th1 (IFNgamma) and Th2 (IL-4) cytokines are produced in response to in vitro PPD-stimulation of PBMC from pulmonary tuberculosis patients and healthy controls. Moreover, the proportion between IFNgamma and IL-4 is tilted in favour of IL-4 in PPD-activated (CD3+ CFSE(low)) cells from healthy persons, who did not develop active tuberculosis during the two-year study time interval. This predominance of Th2 effectors points to the need to further investigate the role of IL-4 in the M. tuberculosis infection.

[Bilateral breast cancer (BBC). Considerations on a series of 20 cases]. / Cancerul mamar bilateral consideratii pe un lot de 20 de observatii.

The aim of this study was to assess breast cancer incidence, diagnostic possibilities in clinical treatable stages and the prognosis in a series of breast cancer patients repeatedly treated in the same unit, by the same team. Diagnostic difficulties in the early stage of the contralateral cancer constitute a proven reality even in our cases. The detection of the second metachronous breast tumor was done and evaluated mostly in an more advanced stage than the initial tumours. This might be explained by the delayed visit to the doctor. Most BBC were lobular carcinoma. Adjuvant therapy--chemotherapy, antiestrogens, ovariectomy--do not prevent the appearance of the second tumoral site.

[Vascular molecular markers for determination of disease free survival (DFS) of breast cancer]. / Markeri moleculari vasculari în determinismul intervalului liber de boala a cancerului mamar.

The heterogeneity of the evolution of breast cancer complicates patient management. The use of vascular markers as prognostic factors is a new and promising tool in medical oncology. Research data of the current decade demonstrate that angiogenesis plays substantial role in growth and spread of malignant tumor. At present, immunohistochemical determination of intratumoral microvascular density represents one of the more promising new prognostic indicators in breast cancer that needs to be further investigated to identify and standardize the method of choice to be tested in prospective clinical studies. Consequently markers of angiogenic activity have receiving increasing attention. By analyzing the evolution of 209 cases of breast cancer enrolled in a prospective study reaching the 5th year of follow up, we provide herein data supporting that Factor VIII and CD34 could be reliable markers for prognosis of DFS. Tumors with lower expression of Factor VIII and CD34 have a better prognostic and lower potential metastatic. The Factor VIII comparative with CD34 represents a more faithful prognostic marker. Angiogenesis markers have also become a putative therapeutic target.

[High values of soluble cytokeratin 18 in breast carcinomas may have different meanings]. / Valorile crescute ale citokeratinei 18 serice in neoplasmele mamare pot avea semnificatii diferite.

We have investigated the cellular and serum CK18 in 26 non-treated primary ductal invasive breast carcinomas. The soluble CK18 (TPS) was detected by chemiluminescent assay, and the cellular CK18 and PCNA expression by immunocytochemistry. Flow-cytometry was used to estimate the amount of DNA in malignant cells. There was a significant correlation between soluble CK18 and the pre-menopausal status (p < 0.05), characterized in our group by a PCNA estimated low proliferation index. We have also found a significant correlation between soluble CK18 and the DNA index (p < 0.01). The intracellular CK18 has correlated with the PCNA expression (p < 0.05), while no correlation could be found between cellular and serum CK18. The values of soluble CK18 may offer information about the treatment-induced cell death, if monitored, while isolated measurements should be interpreted cautiously. Elevated levels of serum CK18 in non-treated carcinomas may rather reflect a high tumor turn-over or perhaps a more intensive tumor cell killing.