Heat shock protein gp96 and CD4+ and CD8+ T-lymphocytes expression as prognostic factors in various molecular types of invasive breast carcinoma.

Breast carcinoma shows extensive clinical and molecular heterogenicity. Glycoprotein gp96 is considered a negative prognostic and predictive factor. Controversy exists over the prognostic role of tumor lymphocytic infiltrates. The goal of this study is to illustrate differences in gp96 and CD4+ and CD8+ T-lymphocytes expression among all immunohistochemical groups of breast carcinoma in relation to the clinical course and outcome of the disease. A retrospective observational study was conducted through processing and analysis of 152 female patient tissue samples previously classified by immunohistochemistry. After immunohistochemical processing, the samples were microscopically analyzed and positive cells were manually calculated in the entire biopsy sample for each patient. In the group of patients with triple negative carcinoma, a significantly higher number of CD4 positive cells in patients with no local recurrence were proven, as well as a significant correlation between a smaller number of CD4 positive cells with a lethal outcome. In the group of patients with Luminal B HER2+ carcinoma, a significantly higher proportion of CD8+ cells in patients with local recurrence were demonstrated. The highest glycoprotein gp96 expression was demonstrated in the group of patients with triple negative carcinoma, while the lowest in patients with Luminal A and Luminal B HER2- carcinoma. This study has shown significantly higher gp96 expression and higher extent of tumor lymphocytic infiltrate in more malignant types of breast carcinoma and represents a significant contribution in affirmation of the prognostic role of these variables.

Case Report of Patient with Relapse of B-cell Lymphoma in the Breast Parenchyma.

We present a patient with relapse of B-cell non-Hodgkin's lymphoma in the breast that was clinically presented as a primary breast cancer. A 72-year old female was treated with chemotherapy and monoclonal antibodies (anti-CD20) due to diffuse large B-cell non-Hodgkin's lymphoma. Complete remission was achieved. Three years later, she was presented with a palpable left breast lump in the perimammillar area of the left breast, dimensions up to 3 cm. Laboratory results were within normal range. Mammography re-vealed a solitary, bilobulated, non-calcified mass of the left breast. On ultrasound, the lesion was hypo-echoic with blurred edges, with posterior acoustic enhancement, measuring 2 × 3 × 7 × 2 cm. Histological findings of ultrasound-guided fine needle aspiration and core needle biopsy were corre-spondent to diffuse large B-cell lymphoma. Pathohistological report showed cells with CD20+/Bcl- 2+/Bcl-6-/MUM-1+/CD3- imunophenotype. The breast parenchyma was infiltrated with B-cell lym-phoma. After diagnosis was confirmed, radiotherapy was initiated. Repeat ultrasound studies showed complete regression of the left breast lesion as did positron emission tomography- computed tomography (PET/CT) scan three months after therapy. In conclusion, the relapse of lymphoma in the breast is very rare. In patients previously treated for lymphoma, differential diagnosis should always include relapse, although it clinically presents itself as a primary breast cancer.

Expression pattern of the endoplasmic reticulum stress protein gp96 in monophasic and chronic relapsing form of experimental autoimmune encephalomyelitis in rats.

Gp96 is the endoplasmic reticulum (ER)-resident molecular chaperone, which is involved in the correction of unfolded proteins, in the activation of proteasome-dependent ER-associated degradation of the misfolded proteins, and in activation of the protein translation that modulates polypeptide traffic into the ER. Furthermore, owing to its peptide chaperone capacity and ability to interact with professional antigen-presenting cells, as well as with growth factors, integrins and Toll-like receptors, it is also endowed with crucial immunological functions acting as a "danger signal" to the innate and adaptive immunity. Considering these properties, in the present study the tissue expression of gp96 was examined during the monophasic and chronic relapsing form of experimental autoimmune encephalomyelitis (CR-EAE), induced in genetically susceptible DA rats by subcutaneous injection of myelin basic protein (MBP) or bovine brain homogenate in complete Freund's adjuvant (CFA). Immunohistochemical analyses were done in periods of attacks and remissions of EAE, and the results were compared with findings in intact rats and those treated only with CFA. The data revealed that the constitutive gp96 expression, found in several neurons and glial cells in the brain and spinal cord of intact animals, significantly diminished during the attacks of CR-EAE. On the contrary, the remission of disease was followed by high upregulation of gp96, mainly in the oligodendrocytes within the white matter, in the neurons of the hippocampal area, as well as in the motoneurons of lumbar spinal cord, suggesting that gp96 might be involved in proteostasis and immune-related pathways linked with the reparative processes in the CNS.

Short-term exposure of mice to gasoline vapor increases the metallothionein expression in the brain, lungs and kidney.

Environmental airborne pollution has been repeatedly shown to affect multiple aspects of brain and cardiopulmonary function, leading to cognitive and behavioral changes and to the pronounced inflammatory response in the respiratory airways. Since in the cellular defense system the important role might have stress proteins-metallothionein (MT)-I and MT-II, which are involved in sequestration and dispersal of metal ions, regulation of the biosynthesis and activities of zinc-dependent transcription factors, as well as in cellular protection from reactive oxygen species, genotoxicity and apoptosis, in this study we investigated their expression in the brain, lungs and kidney, following intermittent exposure of mice to gasoline vapor. Control groups consisted of intact mice and of those closed in the metabolic chamber and ventilated with fresh air. The data obtained by immunohistochemistry showed that gasoline inhalation markedly upregulated the MTs expression in tissues which were directly or indirectly exposed to toxic components, significantly increasing the number of MT I+II positive cells in CNS (the entorhinal cortex, ependymal cells, astroglial cells in subventricular zone and inside the brain parenchyma, subgranular and CA1-CA3 zone of the dentate gyrus in hippocampus and macrophages-like cells in perivascular spaces), in the lungs (pneumocytes type I and type II) and in the kidneys (parietal wall of Bowman capsule, proximal and distal tubules). The data point to the protective and growth-regulatory effects of MT I + II on places of injuries, induced by inhalation of gasoline vapor.