VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis

Endocrine Gland-Derived Vascular Endothelial Growth Factor/Prokineticin-1 in Cancer Development and Tumor Angiogenesis

A lot of data suggests endocrine gland-derived vascular endothelial growth factor (EG-VEGF) to be restricted to endocrine glands and to some endocrine-dependent organs. Many evidences show that EG-VEGF stimulates angiogenesis and cell proliferation, although it is not a member of the VEGF family. At the time, a lot of data regarding the role of this growth factor in normal development are available. However, controversial results have been published in the case of pathological conditions and particularly in malignant tumors. Thus, our present paper has been focused on the role of EG-VEGF in normal tissues and various malignant tumors and their angiogenic processes

High Ki-67 expression is associated with prolactin secreting pituitary adenomas

Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenomas. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method. Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin (STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by counting approximately 1000 nuclei of the tumor cells at ×400 magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting adenomas)

C CA AS SE E R RE EP PO OR RT T Neural granular cell tumor. A case report

Abstract It is presented the case of an old female with a solitary tumor at the level of the thorax. The specimen was processed using the routine histological technique and slides were stained with conventional morphologic, histochemical and immunohistochemical methods. On Hematoxylin-Eosin stained slides were noticed large cells with acidophilic cytoplasm, with granular pattern. S100 protein was intensely expressed in all tumor cells and neuron specific enolase was moderate positive. CD68 positive reaction was considered the expression of lysosomes accumulation in the cytoplasm of tumor cells. Histological and immunohistochemical findings are consistent with the diagnosis of neural granular cell tumor

Triple negative breast cancer: The kiss of death

One of the most controversial women malignancies, triple negative breast cancers (TNBCs) are critically overviewed here, being focused on data useful in clinical practice or to improve the therapy and patients survival. TNBCs "choose" young women and its "kiss" is, unfortunately deadly in most cases. Currently, few sparse data are available in literature concerning the origins of TNBC. Vasculogenic mimicry detected in TNBCs, seems to be determined by a population of CD133+ cells and may be stimulated by different pharmacological agents such sunitinib. Despite the fact that TNBCs do not usually metastasize through the lymphatic pathways, TNBCs may be characterized by lymphatic invasion and by an increased lymphatic microvascular density. If TNBCs treatment depends on the molecular profile of the tumor, the same statement may be postulated for TNBCs metastasis. Whether metastases have a similar phenotype as the primary tumor remains an enigma. Therefore, the question: 'Could TNBC be subject to a standardized, unanimously accepted therapeutic strategy or is it strictly subclass-dependent?' remains to be further investigated

HETEROGENEITY OF C ERB B FAMILY MEMBERS EXPRESSION IS RELATED TO CELL MORPHOLOGY AND IMMUNOPROFILE IN PITUITARY ADENOMAS

Purpose. Epidermal growth factor receptor (EGFR, HER1) and human epidermal receptor 2 (HER2) assessement in pituitary adenomas related to hormone profile. Design and methods. For 60 retrospective cases of pituitary adenomas, we established the histopathologic diagnosis by using morphological stains, followed by case selection for immunoprofile and EGFR and HER 2 assessement. Results. More than one third of the studied pituitary adenomas (33,33%) were positive for HER2, with membranar pattern in basophilic cells and with predominantly cytoplasmic, granular pattern for acidophils cells. HER2 immuno-expression characterized PRL secreting adenomas (p=0.005) and associations between FSH-LH (p< 0.001) TSH-FSH (p=0,024) and TSH-LH (p=0.028). In situ hybridization confirmed HER2 gene amplification in 33,34% out of all positive cases for HER2 by immunohistochemistry. EGFR positivity was found significantly for GH-prolactin (p=0.000) and prolactin-ACTH (p=0.045) co-expressing pituitary adenomas, peritumoral macrophages and folliculostellate cells. Conclusions. Differential HER2 and EGFR expression related to hormone profile heterogeneity can define different subclasses of pituitary adenomas and could explain clinical, prognostic and therapeutic heterogeneity which are observed in clinical practice. Our results support re-classification of pituitary adenomas based on molecular approach which should include markers with well certified prognostic and therapeutic impact

EXPRESSION OF CK5 BASAL CYTOKERATIN DURING METASTATIC DEVELOPMENT OF BREAST CARCINOMA

Objective. Breast cancer is a one of the most common cancers in females worldwide. Basal cytokeratin CK5 represent the marker of progenitors for glandular and myoepithelial lineages of mammary epithelium. During epithelial differentiation there is a gradual decrease of CK5 expression. The purpose of this study was to compare the expression of basal cytokeratin CK5 vs hormone receptors, HER2, Ki67 and molecular subtypes immunohistochemically defined in the primary breast carcinoma of NST type and axillar lymph node metastasis. Material and Methods. We processed immunohistochemically 91 invasive breast carcinomas of NST type and their ipsilateral axillar lymph node metastasis (LNM). Results. The majority of primary tumors were evaluated as CK5 negative (78 cases/85.7%). The majority of cases were evaluated as Luminal B (50 cases/54.9%) and Luminal A (28 cases/30.8%) tumors. The HER2 subtype was confirmed in 8 cases/8.8%, 5NP in 3 cases/3.3% and Basal-like in 2 cases/2.2%. The parallel comparison of CK5 expression at both sites, primary and metastatic, revealed that this marker is not stable during metastatic progression. The molecular subtypes were not stable during metastatic process in 21 cases/23.1%. Conclusions. The majority of NST invasive ductal breast carcinomas are CK5 negative. The molecular subtypes and CK5 are not stable during metastatic process. Cancerous cells prefer to lose this marker in the lymph node environment. The presence of cases with simultaneous expression of CK5 and hormone receptors is an open field to debate the existence of other, transient molecular subtypes. We expect a further confirmation in larger study groups

O OR RI IG GI IN NA Involution of the thymus: a possible diagnostic pitfall

Abstract There were investigated 22 cases from which the thymic tissue was removed either during surgery for cardiovascular malformations (n = 14), or for myasthenia gravis (n = 8). Histological sections were stained with routine morphologic methods, and immunohistochemistry was performed for cytokeratin, CD20, CD3, and S100 protein. Aspects characteristic for thymus involution were found in 11 cases without myasthenia gravis and in all cases with myasthenia gravis. Morphological changes of the thymus of involution are age-dependent. There were characterized stages of involution, with special reference to cortical -medulla inversion, lymphocyte depletion and sequestration. In advanced-stage of involution, epithelial cells are arranged in cords or compact islands, and could mimic a thymoma or a metastatic carcinoma. The immunohistochemical profile is similar but not identical to the active thymus. We noticed a decreased expression of cytokeratin, and a reduced number of CD3, CD20, and S100 positive cells. Morphologic and immunohistochemical peculiarities of the thymus of involution are discussed in relation with the specific pathology of the organ