Correlation of folate receptor alpha expression with clinicopathological parameters and outcome in triple negative breast cancer.

Folate receptor alpha (FRα) is a membrane-bound protein with a high affinity for folate, which is necessary for the biosynthesis of amino acids and nucleotide bases. It has been shown to be a potential prognostic and therapeutic target, primarily in lung and ovarian cancer, as well as in breast cancer. The aim of this study was to examine FRα expression in a cohort of patients with triple negative breast cancer (TNBC), in correlation with clinicopathological parameters and prognostic factors. By using polyclonal FRα antibody on archival paraffin blocks immunohistochemistry was performed. To evaluate the expression of FRα, H-score was used, which marks both the proportion of stained cells and the intensity of staining. Statistical analysis correlating FRα expression with clinicopathologic parameters and clinical outcome were performed. FRα was expressed in most of the patients (85%). Significant correlation of expression and histologic grade (Mann Whitney U test, P = 0,03) and type of tumor (P = 0,02), was found. It was noticed that with higher Ki-67 proliferation index values, H-score has lower values (r = -0,284, P = 0,006). Multivariant regression analysis (Cox regression, Stepwise method) showed H-score as a significant predictor for the risk of disease recurrence (OR = 1,005, P = 0,04). No correlation between FRα expression and overall survival (OS) and disease-free survival (DFS) was found. In conclusion, FRα is highly expressed in TNBC, and, given the correlation with clinicopathological parameters, subpopulation of patients could be identified that could be potential targets for new therapeutic perspectives in the treatment of this breast cancer subtype.

Current organisation of clinical cytology in Croatia.

Current cytological service in Croatia is organised in 46 cytological organisational units in 23 towns with total of 350 employees: 101 specialists of clinical cytology, 20 residents in clinical cytology, 141 cytotechnologists (cytoscreeners), 45 health technicians, and 25 administrators and 18 auxiliary personnel. In spite of employment of significant number of cytotechnologists in the last ten years, there is still an unacceptable ratio of number of cytologists and cytotechnologists (1:1.4) which is the result of unresolved education of cytotechnologists which should be permanent, complete and acknowledged. Education and scientific promotion of cytologists is continuous and today our profession has 31 masters of science and 9 doctors of science, one of which is the assistant professor, and four of them are associate or full professors at medical schools in Zagreb and Osijek. Croatian cytology, in average, is in its "best years", i.e. an average cytologist is 46-years-old and cytotechnologist is averagely 43-years-old, but "suffers" from personnel deficit. With regard to the type of activity, the most numerous are units dealing the entire diagnostic cytology (72%), 13% general cytology without gynaecological cytology, while 15% are engaged in one diagnostic field (gynaecological, pulmological or thyroid cytology). According to accessible data, total of 770996 cytological examinations were done in Croatia in 2008. The increasing application of additional methods (cytochemical, immunocytochemical, molecular, cytogenetics and computer-assisted image analysis) has become a trend in numerous cytological units. Exclusively morphological analysis of standard stained samples is performed in 37% of units, morphological and cytochemical staining methods are used in 17% of units, and additional immunocytochemical methods in 30% of units. According to the long tradition of cytology in Croatia, that has progressed thanks to the enthusiasm and great effort of our teachers, we believe that the following generations of cytologists will continue working on its improvement and will be able to concord the basic cytomorphology and sophisticated diagnostic procedures with other diagnostics, to stay the field of optimal results in the shortest time with the reasonable price.

Fine needle aspiration biopsy of follicular thyroid tumors.

US-guided fine needle aspiration cytology is currently the best diagnostic tool for thyroid nodules. The aim of this research was to make a detailed and objective determination of the morphological characteristics of cells in cytological smears in an attempt to distinguish benign from malignant follicular tumors. The research included 62 patients with cytologically diagnosed follicular or oncocytic tumors, and 15 patients with nodular hyperplasia. Echographic findings were divided into three groups: isoechogenic, hypoechogenic and hyperechogenic nodules. We analyzed the cellularity of the smear, cohesion between follicular cells, acinar formations, bare nuclei, characteristics of the nucleus and the cytoplasm, and the presence of colloid. The statistical analysis of cytological parameters has indicated that none of the cytological parameters alone is discriminating enough between non-tumor and tumor changes, or benign and malignant follicular thyroid nodules. The analysis of age, sex, nodule size and ultrasound findings has not shown the correlation between any of these parameters with the malignant or benign follicular tumors. The cytological analysis of the smears for patients with follicular tumors, in combination with clinical data and other diagnostic methods, contributes to more precise diagnostics, but is not sufficient for the differentiation between benign and malignant follicular tumors.

Granular cell tumor--clinically presented as lymphadenopathy.

Granular cell tumors are relatively uncommon benign lesions occurring in almost any part of the body. We report the cytological diagnosis of granular cell tumor in 25-year-old male patient who presented with an inguinal mass clinically suspected to be a lymphadenopathy. Fine needle aspiration revealed polygonal cells with abundant, granular cytoplasm and eccentrically located vesicular nuclei and inconspicuous nucleoli. The histopathological examination of the surgical excision confirmed the diagnosis. If resection is complete, local surgical excision is curative for benign granular cell tumors. Granular cell tumor has a characteristic cytological appearance, and fine-needle aspiration cytology has been suggested to be diagnostic modality of choice.

A model of dual circulation in liver acini with hypoxia regulated adenosine secretion.

It was postulated by W.W. Lautt that the hepatic artery flow compensation for changes in portal vein flow (the 'hepatic arterial buffer response') is regulated through the portal blood washout of adenosine from the small fluid compartment that surrounds the hepatic arterial resistance vessels. It is presumed that the adenosine secretion there is constant and independent of oxygen supply or liver demand. It was reported by others that liver secretes variable quantities of adenosine and that secretion is related to the level of liver hypoxia. This paper is an attempt to describe a model of acinar circulation without sources of constant adenosine secretion. The presented model is based on the fact that portal blood enters acinar space near the vascular stalk in the zone 1, while most of the arterial branches empty one-third from the interlobular septa, at the beginning of the zone 2, just downstream from the zone 1. Another important characteristic of liver architecture is that near 5/9 of lobular volume is in the zone 1. Liver cells in zone 1 are well oxygenated by the portal blood and they have low adenosine secretion that might seem almost constant. Since most arterial branches empty more peripherally, the zone 1 normally does not depend on the arterial circuit and most of arterial branches are governed by the adenosine secretion from the upstream zone 1. Low portal flow, would increase adenosine secretion from the zone 1 and thus dilate numerous downstream arterial resistance vessels. An increased flow from these arterial vessels would compensate any decrease in the portal flow. Zones 2 and 3 probably have higher adenosine secretion rates since the oxygenation depends on the amount of added arterial blood and on the liver cell metabolism. Some of the arterial branches in those zones are probably open all the time, preserving them zones from hypoxic injury. Since the main point for arterial inflow is concentrated downstream from the zone 1, in cases of low portal pressures, or elevated upstream resistance, some of the arterial blood might leave the acinus in retrograde direction via the portal branch and enter some other acinus as a part of portal blood. These arterio-portal communications might be important in cases of low or none portal flow when zone 1 is in hypoxia. In the 3D liver space with tightly packed acini, very complex and ever-changing patterns of combined antegrade and retrograde flows can be expected.

[Dominant form of Diamond-Blackfan anemia]. / Dominantno nasljedni oblik Diamond-Blackfanove anemije.

Diamond-Blackfan anaemia (congenital hypoplastic anaemia) is a rare hereditary disease with isolated congenital hypoplasia of red blood cells precursors in bone marrow, and its important characteristic is successful treatment. Most of the patients become symptomatic in the first year of life and it lasts lifelong. In 25% of patients with Diamond-Blackfan anaemia 19q13 gene mutation was detected, and recent findings suggest another gene located on 8p23.3-p22 chromosome. Two sisters with mild clinical manifestations of Diamond-Blackfan anaemia were studied at the Department of Paediatrics in the Osijek University Hospital. First symptoms in both of these patients were noticed at the age of 5 months. Bone marrow puncture showed isolated hypoplasia of morphologically normal red blood cells precursors. Patients responded well to corticosteroid therapy. All members of patients' family were genetically tested for known loci for this disease, but tests showed no genetical abnormalities. Diagnosis was made by clinical symptoms, cytological findings and ex iuvantibus. We believe that patients are in the group with good outlook, since minimal steroid therapy stabilized their symptoms, and they developed no addiction either to high-dosed steroids, or to transfusions.