Low p27(Kip1)expression is associated with poor prognostic factors in breast carcinomas.

PURPOSE: This study was designed to detect the presence of the p27(Kip1) protein expression in breast carcinomas and corresponding axillary lymph node metastases, as well as any potential correlation of p27(Kip1) with factors of tumor progression and prognosis (estrogen receptors-ER, progesterone receptors-PR, c-erbB-2, p53). PATIENTS AND METHODS: 44 primary breast cancers and positive axillary lymph nodes from 24 cases were examined by immunohistochemistry. RESULTS: 19 out of 44 (43.18%) tumor specimens expressed the p27 protein, whereas 25 (56.82%) specimens expressed it only at low levels or were negative. Absence of p27 correlated significantly (p < 0.05) with a negative status for ER and PR receptors. The presence of p27 protein in primary tumors was always associated with positive expression in the corresponding nodal metastases. CONCLUSION: Our results indicate a correlation between lack or low levels of p27 protein expression and the absence of hormone receptors. The p27 phenotype is preserved from the primary breast tumors to the corresponding axillary lymph node metastases.

Sequential phenotype changes in progressive lesions of breast carcinoma.

Malignant transformation is the result of genetic events, translated into sequential acquisitions of multiple abnormalities in the control of cellular growth and cell cycle regulation. We determined the expression of the estrogen receptor (ER), progesterone receptor (PR), c-erbB-2 and p53 gene products in a patient with mixed (ductal and lobular) invasive breast carcinoma bearing different coexisting lesions. The purpose of the study was to establish a possible correlation between the expression pattern for these molecules and the histological appearance of the breast tumor. Our results showed no positivity for ER. PR expression was restricted to normal epithelium, simple hyperplasia and in situ carcinoma. c-erbB-2 was detected in all lesions with the exception of normal epithelium and immunostaining for p53 was found positive only in in situ and invasive carcinoma. These findings support the hypothesis of tumorigenesis as a multistep process and as a sum of changes, each representing an advantageous acquisition for the malignant cells' behavior. The loss of hormone receptors' expression occurred as an early event in this case, while the p53 mutations were found only in more advanced neoplastic lesions.

[Lymphocyte traffic in the events that follow lymphocytes activation in the germinal centre]. / Traficul limfocitar si evenimentele ulterioare activarii limfocitelor în centrul germinal.

After their maturation, lymphocytes migrate from the primary lymphoid organs to the secondary lymphoid organs and tissues. Once in the secondary tissues the lymphocytes do not simply remain there; many move from one lymphoid organ to another via the blood and lymph. This process allows a large number of antigen-specific lymphocytes to come in contact with their appropriate antigen in the microenvironment of the peripheral lymphoid organs and this is important since lymphocytes are monospecific and only a limited number of cells are able to recognize and interact with a particular antigen. When B cells are activated by antigen, with the help from the T cells, they mature either into AFCs (Antibody-Forming Cells), or they develop into memory cells. The germinal centers in various lymphoid tissues represent the sites of the immune response development and memory B cells generation. At these sites, the B cells undergo active hypermutation of the variable genes, a process that can lead to death by apoptosis for some cells.

[The reflection of the dynamics of the serum markers CA l5.3 and CEA in breast cancer]. / Reflexia dinamicii markerilor serici CA 15.3 si CEA în cancerul mamar.

The aim ao this study was to evaluate the significance of the usual analysis of CA 15.3 test in breast cancer, the efficiency of different therapies (by observing the CA 15.3 dynamics) and to find out the possible connection between CA 15.3 serum level, CEA and the cancer course. By the study of 23 patients diagnosed with breast cancer in various stages, we managed to determine the serum concentration of CA 15.3 and CEA using DELFIA, namely ELISA method, before and after individual therapy. Before therapy, we found pathological CA 15.3 levels in 13 patients (56.5%) and after treatment in 16 patients (69.56%). After individual therapy, we also measured the seric level of CEA, within normal ranges in 3 patients with advanced metastatic disease, who also presented pathological values for CA 15.3. Based on the clinical and experimental data we noticed the connection between pathological values of CA 15.3 and IIA, IIB stages (at significant recurrence risk). The significantly increased levels of CA 15.3 and CEA could be correlated with the locally advanced and metastatic forms.

[NK cells in the physiology of the fetomaternal relationships]. / Celulele NK în fiziologia relatiilor materno-fetale.

The NK cells are large granular lymphocytes that are found as approximately 2-15% of the global peripheral lymphocytes. As endometrial granulocytes, they represent 70% of the decidual leukocytes during the first trimester of pregnancy, with a progressive decreasing until term. The complex actions of these numerous and active cells, consist in: 1) placental regulation and control, based on the receptors for the HLA--G and HL--C antigens, that are trophoblast specific and act as universal inhibitors of the NK cells; 2) secretion of a large range of cytokines as IL-1, TNF alpha, IL-8, TGF, IFN gamma, GM-CSF, CSF1 which regulate the trophoblastic proliferation, differentiation and invasion; 3) removal of abnormal trophoblastic cells, which may appear in such a proliferating cell population; 4) infectious protection of the placental unit, due to their unspecific cytotoxic effect. In conclusion, the NK lymphocytes have important implications in the formation of the decidua, as the maternal side of the fetomaternal interface and they are deeply involved in the evolution of normal pregnancy concerning the nutritional, hormonal and immunologic aspects.

[The correlation between the clinical stage and multimodal treatment in breast cancer expressed in the 5-year survival rate]. / Corelatia dintre stadiul clinic si tratamentul multimodal în cancerul mamar, exprimata în rata de supravietuire la 5 ani.

The survival rate in 143 patients with breast cancer followed up for 60 months has been evaluated by the regression Cox method and life table method, a number of representative variables for tumor and/or host being taken into account. The Cox model coefficients pointed out the following factors to positively influence the survival: age, premenopausal status, surgery, radiotherapy and complete chemotherapy (6-12 cycles). Negative and highly negative values recorded within variables: tumor over 5 cm, the presence of metastases, Karnofsky index less than 80 and the postmenopausal status generally correlated with the disease in advanced clinical stages. An apparently better survival in patients who underwent radiotherapy as compared to those who underwent an associated radiochemotherapy could be the result of the preferential associated treatment in advanced stages. The optimal intensity of chemotherapy positively influences the survival, except in late stages, suggesting the necessity of chemotherapy in initial stages.

[The evolution of the natural-killer-dependent cytotoxic activity during normal pregnancy]. / Dinamica citotoxicitatii natural--killer (NK) dependente în evolutia sarcinii fiziologice.

The fetus was compared to an allograft because paternal antigens are also expressed. Even the analogy is not a real one, the main steps of the rejection phenomenon are relevant for the understanding of the complex materno-fetal interactions as the large granular lymphocytes are the first immune cells which invade the graft. Due to the important role of NK cells in the cell mediated immune response, the purpose of this paper was to assess the NK cell dependent cytotoxicity during normal pregnancy. The study was performed on a test group of 52 normal gravidas, in the Ist, IInd and IIIrd trimester and a control group of 20 healthy nonpregnant women with similar age and parity averages. The cytotoxic activity of the NK cells was measured in a 51Cr release assay against K 562 cell line. The results were expressed as the cytotoxicity index (%) and showed a statistically significant decrease for all gravidas compared to controls, mostly for the IInd trimester. The trend of the NK cytotoxic activity during normal pregnancy suggests the deep involvement of the NK cells in the mechanisms acting at the fetomaternal interface.