Mira Krstulja

EXPRESSION OF MONOCYTE CHEMOTACTIC PROTEIN-1 IN HUMAN INVASIVE DUCTAL BREAST CANCER

Monocyte chemotactic protein-1 (MCP-1) is a chemokine involved in the macrophage infiltration of tumor tissue. Tumor associated macrophages (TAMs) are a population of mononuclear-phagocytic cells, which can express complex functions related to tumor biology. The present study was designed to analyse the expression of MCP-1 in parenchymal and stromal elements on frozen sections of 27 breast invasive ductal carcinomas not otherwise specified (NOS) by immunohistochemistry. The expression of MCP-1 in tumor parenchyma and the degree of tumor differentiation were assessed. MCP-1 was detected in the parenchyma in 15 of 27 ductal carcinomas. Positive immunoreactivity manifested as diffuse, homogeneous, moderate or strong, cytoplasmic staining, confined to tumor epithelium. Generally, MCP-1-negative tumors tended to be well differentiated, while chemokine-positive tumors exhibited a low level of differentiation. MCP-1 immunoreactivity was also present in TAMs (CD68 positive cells) in 23 of 27 tumors, and in endothelial cells in 11 of 27 tumors. These results indicate that parenchymal and, more variably, stromal elements of human invasive ductal carcinomas NOS can express MCP-1 in vivo. Additionally, these findings suggest that MCP-1 expression in tumor parenchyma is correlated with the histological grade of ductal invasive breast carcinoma.

VEGF Expression is Associated with Negative Estrogen Receptor Status in Patients with Breast Cancer

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.

Expression of Beta-1 Integrins on Tumor Cells of Invasive Ductal Breast Carcinoma

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.

Cytoplasmic EGFR staining and gene amplification in glottic cancer - a better indicator of EGFR-driven signaling?

Although enhanced epidermal growth factor receptor (EGFR) signaling has been connected with glottic cancerogenesis, the precise mechanisms of its activation still remain unclear. The aim of the present study was to examine EGFR on protein level, confronting cellular pattern of expression and EGFR gene amplification in glottic carcinomas. Tissue microarray technology was applied for uniformity of results. Biopsy specimens of patients with glottic squamous cell carcinoma and simple hyperplasia (control samples) were immunostained for EGFR. Immunohistochemical EGFR reaction was analyzed as membrane and cytoplasm positive and compared with the presence of gene amplification obtained by fluorescent in situ hybridization (FISH) analysis, obtained previously on a large group of patients. The cytoplasmic distribution of the EGFR staining appeared as a primary property of some squamous carcinoma cells; different from the membranous reaction, the reactions were mutually exclusive. Significantly higher scores of cytoplasmic EGFR staining were found in carcinomas with gene amplification when the cell reaction was examined in the basal and suprabasal layer. Our results suggest that EGFR expression in squamous cell carcinoma is different with regard to tumor cell position in carcinoma with ERGF gene amplification, which could be a new indicator of differently driven EGFR signaling in glottic cancer. Such results with cellular pattern distribution of EGFR protein are worthy of further research.

Merkel Cell Carcinoma Arising in the Ear Canal

A case of rare tumor, Merkel cell carcinoma, located in the ear canal of a 25-year-old woman is presented. A polypoid tumor mass was extirpated, and tympanoplasty was done at the first operation, whereas at the second operation, all the bones of the ear canal were removed. Epitympanum and cavum were filled with tumor, and the tumor mass was removed in toto. The histopathology and immunohistochemical staining characteristics of tumor confirmed the presence of Merkel cell tumor. Postoperatively, radiation therapy to the tumor bed was completed. There was no clinical or radiographic evidence of recurrence or metastasis of Merkel cell tumor for 3 years.

Thoracic aortic aneurysm rupture into the esophagus.

A 73-year-old female with a history of mild hematemesis was transported to the hospital emergency department. Although she was under the influence of alcohol, the patient remained alert. She had hypotension (100/60 mmHg) and anemia (red cell count 2.80 9 10/L; hemoglobin 86 g/L; hematocrit 0.265 L/L). A digital rectal examination performed after admission revealed black, formed stool. She had medical comorbidities of choleithiasis and a history of alcohol abuse. An emergency upper digestive endoscopy was performed immediately, which showed blood clots and fresh blood in the stomach. There was a protrusion near the gastro-esophageal junction but, despite intensive examination, the immediate place of bleeding could not be identified. As the exact site of bleeding was undeterminable diluted adrenaline was injected into the suspected area of hemorrhage at the fundus of the stomach. The patient was transferred to the intensive care unit where intravenous fluids and a blood transfusion were administered. The patient became stable upon aggressive fluid administration and a surgeon was requested for consultation. The surgeon advised the hospital staff caring for the patient to continue with the conservative therapy course (that included frequent monitoring of hemodynamic parameters) until the exact bleeding site could be identified. However, a few hours after admission the patient started to vomit blood vigorously and became hypotensive. A diagnosis of thoracic aortic aneurysm (TAA) with esophageal fistula was made. Emergency surgical treatment was ordered. The patient was transferred to the operating room, where she collapsed and became unconscious and asystolic. She died one hour later despite critical life support measures. Although a complaint of medical negligence was not raised in this case, an autopsy was performed in accordance with Croatian law, which requires that all patients who die within 24 h of hospital admission have to be examined by a certified pathologist. The autopsy revealed a large spherical aneurysm, 5 cm in diameter, of the descending thoracic aorta; 1.5 cm below the tracheal bifurcation (Fig. 1). Rupture into the esophagus was observed, with an aorto-esophageal fistula (AEF) around 2 cm in diameter (Fig. 1). On the aortic side of the fistula, the opening was covered with laminated thrombus that was firm on palpation. The rest of the intima of the thoracic and abdominal aorta did not exhibit severe atherosclerotic changes. The stomach was completely filled with blood and clots (about 800 mL); with bloody and tarry contents in the intestines. Tissue histology around the fistula (the aortic and esophageal wall) showed hemorrhage, inflammation and fibrosis. The aortic wall was severely infiltrated with neutrophils around the rupture site (Fig. 2). The laminated thrombus appeared to have acted as a lid covering the fistula opening. There was no histological evidence of cystic medial degeneration in the aortic wall. No significant pathology was observed in any other organs.

Deskriptivna i funkcionalna definicija jezgrice – put prema terapiji raka

Modern tumour therapy should be target specific and comprehensive. Recent clinical trials test small molecular inhibitors of transcription of ribosomal genes and activators of apoptosis. We treatise on models of activation of the suppressors of tumour growth acting in the nucleolar domain. Tumour cells demonstrate a disordered protein regulation and mutation of P53 gene which codes for a suppressor of growth. Therapy is guided by pathogenesis. Modern disease definition is based on etiopathogenesis of cell stress, wherein participate numerous organelles, including the nucleolus. Nucleus and nucleolus are forms seen on light microscopy. This presentation focuses on the description of the visible correlate of the notion of “nucleolus”. Further to this, acid non-histone proteins which gather around the transcriptional machinery of RNA polymerase I are described, and the significance of their visualisation towards the alteration of the definition of nucleolus is pointed out. Besides being a particle within the nucleoplasm and a subnuclear organelle, the nucleolus is visualized through its functional structures – the AgNORs. The AgNOR proteins have a role in nucleolar stress. The aim of this article is to discuss the nucleolar stress.

Proliferation of endothelial cells in neoangiogenesis of human cortical glioblastoma

In 1982 Vilanova et al. quantitatively described the neovessel area in glioblastoma and suggested zonal differences in vessel surface area. In this study we investigated specific cell proliferation and angiogenic patterns in the vessel compartment of cortical glioblastoma. We used Ki67, CD34 and SMA double immunohistochemical staining to quantitate vascular patterns and cell specific proliferation and presented glioblastoma with several parameters of angiogenesis. Endothelial cell proliferation was higher in complex and bizzare neovessels than in the simple and sprouting glioblastoma neovessels. There was a higher frequency of sprouting simple vessels in close proximity to the palisade and a higher frequency of bizzare vessels in the microzone distant to the palisade. Quantitatively presented for the first time, the neovessel proliferation patterns support cortical glioblastoma compartmentalization. The data obtained are relevant to medical doctors using neoangiogenesis in diagnosis, prognosis and therapy of neoplasia. The results obtained in 15 patients call for further investigation of endothelial cell/pericyte relationships and glioblastoma compartmentalization.