2nd Dept of Pathology

Precise and standardized response evaluation enables clinicians to tailor primary systemic therapy (PST). Breast cancer patients underwent (18)F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) before and after PST. Response was assessed by maximal Standardized Uptake Value (SUVmax); morphological changes and Ki-67 labeling index (LI). In parallel response assessment was performed by European Organization for Research and Treatment of Cancer (EORTC); PET Response Criteria in Solid Tumors (PERCIST); World Health Organization (WHO); Response Evaluation Criteria in Solid Tumors (RECIST); Chevallier and Sataloff classifications, and by a novel Ki-67 score. Accuracy of different scoring systems was evaluated. In the 42 enrolled patients, SUVmax, size, and Ki-67 LI decreased significantly on PST. Significant differences between patients with versus those without pathological complete response were observed for pre-treatment Ki-67 LI and SUVmax and...

Whether a breast carcinoma is HER2-positive or -negative has a significant impact on its treatment. The most common method of evaluating the HER2 status of breast tumors is immunohistochemistry. Preliminary data suggest that the proportion of HER2-positive tumors in Hungary shows a wide range from laboratory to laboratory, and overall it just reaches the bottom levels of the incidence reported in the literature (12% 3+ and 11% 2+ cases). A 3-round quality-control test was implemented on a voluntary and anonymous basis. Participating laboratories had to immunostain and evaluate 4 tumor samples per circulation, according to their daily routine. The authors of the present article gave an expert opinion in all cases, and this was compared with the individual laboratories' evaluation and the real FISH-controlled HER2 status of the samples. On the basis of the participants' and experts' evaluation 22/218 and 21/218 HER2 3+ cases were underscored, corresponding to an underevalu...

The expression and the distribution of tenascin as well as the extent of blood vessel formation (angiogenesis) were investigated in 70 invasive human breast carcinomas. Formalin-fixed, paraffin-embedded specimens were stained with monoclonal antibody against tenascin-C (DAKO and Biogenex). Anti-CD31 antibody (Biogenex), an acknowledged marker of stromal angiogenesis, was used to detect endothelial cells. Tenascin immunostaining was positive in the tumours around the persisting normal ducts, around tumour-cell nests, in the neostroma, in some tumour cells, and it was found in or around vascular channels. Tumour vascularity was assessed by quantitative vascular grading (Chalkley point count) and was related to the localization and intensity of tenascin immunoreactivity. 19 tumours (27.1%) were scored as low, 35 (50%) as medium, and 16 (22.9%) as having a high vascular grade. The positive correlation between the vascular grade and the tenascin immunopositivity in tumour stroma was observed. Our results suggest that tenascin expression may be associated with endothelial cell activation and may play an important role in tumour angiogenesis.

Osteopontin, a non-collagen, Ca-binding phosphoprotein, plays roles in both physiological and pathological mineralisation processes. Its expression may be severely altered in malignant tumours. To investigate the presence of this protein in breast tumours showing mammographic microcalcifications. In this study the authors investigated immunohistochemically the osteopontin expression in 26 breast tumours. The elemental composition of the microcalcifications of the same tumours was also examined with energy dispersive spectrometer linked to a scanning electron microscope. Osteopontin expression was found within the tumours in the tumour cells, in vascular smooth muscle cells, in the myoepithelial cells of the normal ducts, and in macrophages. Extracellular osteopontin positivity was seen around calcified foci. There was no correlation between osteopontin positivity and the examined prognostic factors: grade, type and size of the tumour, axillary lymph nodes status, or age. Two types o...

In our recent investigation, angiogenesis was evaluated and quantified by immunohistochemical evaluation of microvessel density (MVD) using claudin-5 (CLDN-5) as a marker for vascular endothelium in 67 canine mammary gland tumours. Computer image analysis was used to measure the intratumoural MVD. Higher intratumoural MVD was detected in malignant simple neoplasms compared with benign tumours. Furthermore, the results of MVD were correlated with histological grade, higher grades being accompanied by higher MVD. In simple adenomas and grade I tubular-tubulopapillary simple carcinomas the intratumoural microvessels were wide and regular in shape with evident erythrocytes in their lumen. In grade III solid carcinomas the microvessels were smaller, less regular and had irregular shape, often without a distinct lumen, and isolated endothelial cells were frequently present. In the complex carcinomas MVD was low and the intratumoural microvessels were mostly irregular in shape without a distinct lumen. The evaluation of MVD by CLDN-5 immunohistochemistry may give useful additional information on the angiogenic potential of breast cancers in dogs.

Claudins are tight junction proteins expressed by epithelial and endothelial cells. The present study has evaluated the expression of claudin-1, -2, -3, -4, -5 and -7 in 115 hyperplastic and neoplastic lesions of the canine mammary gland and compared this expression with that of normal mammary epithelium. The lesions studied included lobular hyperplasia (n=15), simple adenoma (n=20), non-infiltrating carcinoma in situ (n=20) and infiltrating carcinomas of histological grades I, II and III (n=20 of each). There was strong expression of claudin-1, -3, -4, -5 and -7 by epithelia within examples of lobular hyperplasia and simple adenoma, and strong expression of claudin-3 and -4 by non-infiltrating carcinomas and all three grades of infiltrating carcinoma. By contrast, there was reduced expression of claudin-5 and -7 by non-infiltrating and infiltrating carcinomas and the expression of these two molecules was inversely correlated with histological grade. Claudin-1 was expressed focally within carcinoma in situ, but this molecule was not detected in any invasive carcinoma. Claudin-2 was weakly expressed within areas of lobular hyperplasia and by simple adenomas, but was not expressed by any carcinoma cells. These results suggest that loss or reduction of expression of claudin-1, -2, -5 and -7 may lead to cellular disorientation, detachment and invasion in canine mammary neoplasia.

The evaluation of the role of claudins (CLDNs) in breast carcinogenesis has recently begun. We investigated the expression of CLDNs 1, 2, 3, 4, and 7 in pT1pN0 and pT1pN1 invasive ductal breast carcinomas. Tissue arrays of 30-30 pT1pN0 and pT1pN1 invasive ductal breast carcinomas of different grades were constructed, and the expression of CLDN 1, 2, 3, 4, and 7 proteins was analyzed using standard and immunofluorescent immunohistochemistry. The results were evaluated by light and confocal microscopy. Regarding CLDN 1, 4, and 7 expressions, differences were noted between normal and tumor cells and also between tumors of different grades, while no remarkable differences were noted between pT1pN0 and pT1pN1 tumors. CLDNs 1 and 7 were found to be downregulated in tumor cells compared to the normal epithelium, while CLDN 4 expression was decreased in grade 1 tumors. CLDN 7 protein was abundant in normal epithelia, and the staining decreased in grade 3 tumors. There were no differences between normal and neoplastic cells regarding CLDN 2 and 3 expressions. As a preliminary result, our observations suggest that the analyzed CLDNs do not promote tumor metastasis. On the basis of our findings, it seems that CLDN 1, CLDN 4, and CLDN 7 may rather have an important role in tumorigenesis or in cell-to-cell adhesion.

A malignant process interferes with the normal 'programme' of extracellular matrix biosynthesis and can modify extensively the structure and composition of the matrix. This effect appears to be attributable to several processes such as direct production of some selected matrix macromolecules by malignant cells or indirectly by the production of factors by malignant cells interfering with the regulation of normal matrix production. Other possibilities may also exist, such as the direct action of an environmental carcinogen on otherwise normal mesenchymal cells. The result is a more or less profound modification of tissue structure and composition with possible feedback effects on the malignant process. Some examples will be discussed such as elastin production by some tumours as well as the biosynthesis of some other selected matrix macromolecules as tenascin and osteopontin by breast tumours. Although the detailed mechanisms of these specific matrix productions is not yet completely elucidated, the rapidly increasing knowledge on the regulation of specific matrix production process and deranged matrix production might represent a new area of crosstalk between cancer research and matrix biology.

The present work is a chapter in an investigation directed by the World Health Organization on the Pathobiological Determinants of Atherosclerosis In Youth (WHO-PBDAY). Our aim was to study the development of atherosclerotic lesions in a young population. Samples of left anterior descending coronary artery (LDC) and thoracic (TA) and abdominal aorta (AA) from five Collaborating Centres (Budapest/Hungary, Havana/Cuba, Heidelberg/Germany, Mexico City/Mexico, Peradeniya/Sri Lanka) of 214 subjects who died aged 15 and 34 were analysed at the Budapest Reference Centre. Slides stained with haematoxylin-eosin and with stains for extracellular matrix were quantitatively and qualitatively evaluated. Mean intima/media (I/M) ratio and the prevalence of type III-IV lesions (preatheroma; atheroma; calcified and fibrous atheroma) were determined and compared in different risk factor (high blood pressure, smoking) groups. High I/M ratio was found in the LDC and type III-IV lesions were frequently ...

This report describes a case of a canine cutaneous grade I mast cell tumour which developed within a lipoma in the right axillar region of an 8-year-old male Boxer. Immunohistologically, the neoplastic mast cells were positive for serotonin, CD45 vimentin and p53, and negative for lysozyme, CD3 and CD79a expression. The proliferation index of the mast cell tumour based on the Ki-67 antigen was 6.1%. Between the benign neoplastic lipocytes and mastocytoma tumour cells intratumoural microvessels were detected by immunohistochemical staining using CD31 and claudin-5 as markers for vascular endothelium.