Immunohistochemical expression of MTA1 and MTA3 in placental tissue of normal and preeclamptic pregnancies.

PURPOSE: The aim of this preliminary study was to evaluate and compare MTAI andMTA3 antigens expression in normal and preeclamptic placentas in order to demonstrate their possible functional relationship during pathogenesis of preeclampsia. MATERIALS AND METHODS: A series including 20 paraffin-embedded placentas, ten of which originated from normal patients and ten from preeclamptic patients, that were examined by immunohistochemistry using the polyclonal antibodies MTAI and MTA3. RESULTS: The results of this study showed a positive nuclear staining reaction against MTAI and MTA3 in both normal and preeclamptic placentas. However, in preeclamptic chorionic villi, cytotrophoblast and syncytiotrophoblast cells demonstrated increased expression of MTAI and MTA3 than in normal ones. CONCLUSION: The present observations indicate a potential role for MTAI and MTA3 for normal human placental function, playing an essential role in the pathogenesis of preeclampsia. Nevertheless, the precise relationship between these antigens' expression and pathological pregnancies remains to be elucidated.

A comparative immunohistochemical investigation of the consequences of chorioamnionitis on the developing human fetal spleen.

INTRODUCTION: The objective of this study was to determine the effects of chorioamnionitis on the extracellular matrix (ECM) structural glycoproteins of the developing human fetal spleen, and their influence on the haematopoiesis and spleen immune system compared to controls. MATERIALS AND METHODS: After elective induced pregnancy termination due to chorioamnionitis or voluntary abortion, paraffin-embedded specimens from the spleen and respective fetal membranes of 90 fetuses were investigated by immunohistochemistry for presence of ECM structural glycoproteins, haematopoietic, and lymphoid cells. Conventional histological examination of the relative fetal membranes was performed. RESULTS: The present results showed no quantitative variations in the expression of the ECM glycoproteins and haematopoietic lineages of the fetal spleen parenchyma at the end of first trimester (in both groups). At the second and third trimesters, acute chorioamnionitis showed a decreased number of the aforementioned proteins, with an increase of granulopoiesis and CD34 progenitor/stem haematopoietic cells. The immune system of the spleen during the third trimester demonstrated a decrease of both B and T lymphocytes, in comparison with controls. CONCLUSIONS: These results suggest that toxins and cytokines generated during chorioamnionitis, seem to influence ECM structural glycoproteins synthesis and release in fetal splenic parenchyma by reducing them, and probably cause further disorders of haematopoiesis and lymphopoiesis.

Thyroid transcription factor-1 expression in invasive and non-invasive urothelial carcinomas.

BACKGROUND: Thyroid transcription factor-1 (TTF-1) has been considered a sensitive marker for thyroid and lung tumors. Recent data have shown that a wide range of neoplasms may express TTF-1. CASE SERIES: We performed an immunohistochemical study in a case series of 42 urothelial carcinomas (UCs) on tissue microarrays sections, in order to investigate how often UCs express the TTF-1 protein and the diagnostic utility of this marker. In addition, we sought to determine by immunohistochemistry if there is an association between TTF-1 expression and the expression of specific basal-like or luminal markers. Five out of the 42 cases (11.9 %) were positive for TTF-1. Three positive tumors concerned non-invasive papillary UCs. There was no association between TTF-1 expression and tumor grade (χ2, p =0.419), stage (χ2, p =0.550) or cytokeratin 5/6 (χ2, p =0.330), cytokeratin 20 (χ2, p =0.995) and estrogen receptors expression (χ2, p =0.268). CONCLUSIONS: UCs may show TTF-1 expression and pathologists should be aware of this phenomenon in order to avoid misdiagnosis, notably in metastatic disease. HIPPOKRATIA 2017, 21(3): 154-157.

Increased B7H4 tissue expression correlates with high CA19.9 serum levels and a worse prognosis of pancreatic adenocarcinoma.

Pancreatic cancer (PC) is a leading cause of cancer death worldwide, especially in Western societies. Its aggressive nature and poor prognosis increase the need for identifying new and more accurate diagnostic and prognostic tools. We studied 41 patients who had undergone radical surgical resection for PC, investigated B7H4 protein expression in the PC tissue specimens of these patients by immunohistochemistry and analyzed several clinical and pathological features. The positive expression of the B7H4 antigen was associated with a negative impact of chemotherapy with gemcitabine on patient survival and also correlated with high CA19.9 serum levels and poorly differentiated tumors. Moreover, patients that overexpressed B7H4 antigen had worse prognosis compared to the ones that did not overexpress B7H4. B7H4 antigen is a negative prognostic marker for PC patients and also seems to express resistance of PC patients to chemotherapy with gemcitabine.

Immature malignant sacrococcygeal teratoma: case report and review of the literature.

Immature malignant sacrococcygeal teratoma (SCT) is a rare tumor, deriving from the three germinal layers and is found in the sacrococcygeal region. It is the most frequent site of teratomas in the fetus. A nut-brown, solid tumor with cystic areas with a ten-cm diameter is reported in the sacrococcygeal region of a female fetus of 23 weeks and with a weight of 308 g. The ultrasound and pathology evaluations revealed characteristics of an immature malignant SCT. The incidence of this tumor type is one in 35,000 to 40,000 live births and females are four times more likely to be affected than males. Sacrococcygeal and cervical teratomas can be diagnosed by prenatal ultrasound and magnetic resonance imaging (MRI). Teratomas are considered an interesting field for research.

B7H4, HSP27 and DJ-1 molecular markers as prognostic factors in pancreatic cancer.

OBJECTIVES: Pancreatic cancer (PC) is one of the most lethal tumors of the gastrointestinal tract. The ability to predict which patients would benefit most from surgical intervention and chemotherapy would be a great clinical tool. A large number of potential markers have been identified lately in pancreatic cancer and their clinical utilities as prognostic tools are under investigation. METHODS: We recruited 41 patients who had undergone radical surgical resection for PC between 2003 and 2010. To investigate the prognostic factors, we evaluated 3 possible markers: B7H4, HSP27 and DJ-1 protein expressions in the tissue specimens of these 41 patients by immunohistochemistry and analyzed the clinical and pathological features of these specimens. RESULTS: The expression of the three antigens was independently associated with a negative impact of chemotherapy with gemcitabine on patient's survival. Moreover, patients who overexpressed B7H4 had worse prognosis than the ones who did not. CONCLUSIONS: B7H4, DJ-1 and HSP27 may be used in the future as prognostic markers that express resistance of pancreatic cancer patients to chemotherapy with gemcitabine.

A case of diffuse bilateral scrotal neurofibroma in a rabbit.

This report details a rare case of diffuse bilateral scrotal neurofibroma complicated by hindlimb paralysis in a rabbit. The animal was evaluated for unusual bilateral scrotal enlargement. After physical examination, ultrasound scan, radiography, computed tomography and laparoscopy, surgical exploration of the scrotum was undertaken. A homogeneous rubbery firm mass was revealed in contact with the subcutaneous tissue expanding to the entire scrotum without involving the testicles. The mass was excised and diagnosed as diffuse scrotal neurofibroma based on histological and immunohistochemical findings (S-100 antibody positive). Over the following month, progressive neurological signs (faecal incontinence, flaccid bladder and hindlimb paralysis) were observed. After excluding central nervous system infection with Encephalitozoon cuniculi, expansion of the neurofibroma to the vertebral canal causing compression of the spinal cord was suspected, although not histopathologically verified.

The challenging trisomy 16: a case report.

BACKGROUND: Trisomy 16 is a very frequent autosomal anomaly accounting for about 2% of first trimester abortions. In most pregnancies the chromosomal genome found in the fetus is also present in the placenta. Confined placental mosaicism is frequently detected in the placental region along with a structurally normal fetus. CASE: We present the case of a 39-year-old primigravida with confined placental mosaicism diagnosed with chorionic villus sampling. Amniocentesis showed a normal karyotype (46, XX). Detailed scanning revealed no structural fetal anomalies, but severe oligohydramnios. CONCLUSION: Diagnosis of trisomy 16 does not necessarily mean that the newborn has anatomical abnormalities.

Molecular diagnosis of CMV infection in fetal aborted tissues in the region of Thrace.

PURPOSE: To detect the incidence of CMV infection in spontaneous abortion in Thrace. METHODS: Genetic material from 143 fetuses aged from 11 to 39 weeks was examined. The material originated from various regions of Thrace. All fetuses and the respective placentas underwent routine histopathology. DNA was isolated from sections of paraffinized tissues. Detection of CMV in the DNA genomic samples was performed using a commercial PCR-based detection kit. RESULTS: From the 143 fetuses that were examined, two were found to be CMV positive. Pathological findings related to inflammatory corruptions were observed in the placentas of 97 embryos, including the CMV infected ones. CONCLUSIONS: This study indicates CMV-DNA infection in 1.4% of aborted fetuses. CMV infection incidence in aborted fetuses is similar to this reported in other European regions. The molecular technique of PCR applied on paraffin-embedded biopsy material is proven to be an accurate, valid and fast method for investigating the CMV infection in aborted fetuses.

Distinct distribution of corticotropin releasing factor receptors in human breast cancer.

The hypothalamic neuropeptide corticotropin releasing factor (CRF) has been found in several types of human cancer, where its biological role is not clarified. In experimental models of breast cancer CRF has been shown to exert anti-proliferative and other actions. Aim of the present study was to describe the expression of the two types of CRF receptors CRF(1) and CRF(2) in human breast tumors. Receptor expression was studied in breast biopsies from patients diagnosed for primary breast adenocarcinoma, obtained from the tumor and the adjacent benign tissue. Gene expression levels were evaluated by real-time PCR following reverse transcription of total RNA extracts. CRF(1) transcripts were found in 23.1% of benign and in 23.1% of malignant biopsies. CRF(2(a)) was found in 22.2% of benign and 36.0% of malignant biopsies. Transcript levels of both receptors did not differ significantly between cancer and benign biopsies from the same tumor. No correlation was found between CRF receptor expression and patient histo/clinicopathological characteristics. Histological mapping using immunohistochemistry revealed positive CRF(1) immunostaining in the cancerous implants and breast ducts, whereas CRF(2) immunoreactivity was localized mainly in the perineural invasions. In conclusion, both CRF receptors were found in breast cancer and the respective benign adjacent tissue. The two CRF receptor proteins presented distinct distribution and subcellular localization, pointing into differing biological roles. CRF receptors could serve as targets of endogenous ligands expressed in the tumor microenvironment, regulating cancer growth.

Intraoperative estimation of sentinel lymph nodes in breast cancer by imprint cytology.

BACKGROUND: Frozen section biopsy has been widely used for intraoperative diagnosis and evaluation of sentinel lymph nodes, so a decision can be made regarding whether to perform axillary clearance during primary surgery. This study aims to discuss the reliability of a simpler and faster method - touch imprint cytology - in the interpretation of metastasis from breast cancer. METHODS: A retrospective review of 41 sentinel lymph node biopsies from patients with breast cancer were examined by intraoperative imprint cytology using rapid Diff-Quick staining. Paraffin-embedded permanent sections were examined using hematoxylin and eosin stained sections from the sentinel lymph nodes in collaboration with the employment of an anti-cytokeratin antibody. RESULTS: Sixteen of all sentinel nodes harbored metastases in the paraffin sections, of which all 16 were identified by imprint cytology (sensitivity 93%). CONCLUSION: Touch imprint cytology is a fast and reliable alternative for intraoperative evaluation of sentinel lymph nodes in breast cancer patients.

High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease.

We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.

Induction of hepatic haematopoiesis with fibronectin expression by EMT stromal cells during the second trimester of development.

In an initial period of vertebrate phylogeny (bone marrow-less vertebrates), lymphohaematopoiesis takes place in numerous organs containing a suitable microenvironment. Among other organs (i.e., gonads, kidney and spleen), the liver is apparently the most appropriate site for homing and differentiation of haematopoietic cell precursors. Interaction between haematopoietic cells and stromal cells is important for regulation of haematopoiesis. Numerous soluble and membrane-bound factors directly regulating haematopoiesis have been documented, but little is known about the effect of the foetal hepatic epithelial-to-mesenchymal transition (EMT) stromal cells' activity and their product-fibronectin, on foetal hepatic haematopoiesis. The binding of late-stage erythroid cells to FN has been well characterised and is believed to be critical for the terminal stages of erythroid differentiation. The intention of this article is to provide a quantitative overview of FN, produced by hepatic EMT stromal cells, in foetal hepatic haematopoiesis during the first and second trimester of development. Paraffin-embedded specimens from the liver of 30 human embryos in the first and second trimesters of gestation were investigated by conventional histology and immunohistology for the presence of FN and specific haematopoietic cell types. The staining intensity, and localisation of FN and haematopoietic markers in sequential sections were examined. Furthermore, double immunohistochemical staining was performed to assess simultaneous detection of FN and haematopoietic markers. FN was expressed in the EMT stromal cells of the hepatic portal triads more strongly during the second trimester than the first. Furthermore, an intense immunostaining for haematopoietic lineages, and especially for erythropoiesis, was observed in the second trimester compared to the first. The results of the double immunostaining disclosed an intimate co-expression of the FN and CD haematopoietic markers. Foetal hepatic EMT stromal cells provide a unique microenvironment that supports the emergence, expansion and maintenance of human foetal haematopoietic development during the mid-gestational stage. FN produced by the EMT stromal cells follows a time course parallel to that of haematopoiesis. We suggest that in foetal liver, phenotypic modifications of EMT stromal cells expressing FN concerning the cell adhesion capacity of the protein are associated with proliferation and differentiation of specific haematopoietic cell lineages during the second trimester of gestation, probably reflecting the increasing demand of the growing foetus for mature erythroid and myeloid cells.

Oral complaints caused from metastases to the mandible and maxilla.

Jaw bone disorders causing oral complaints are common in primary care settings. Most of these conditions are of a chronic and benign nature. However they also may be the symptoms of a primary or secondary malignant process in the bone. The most common malignant bone tumor is metastatic carcinoma, and tumors arising in the breast, prostate, thyroid, lung and kidney have a special propensity to spread to bone. Yet metastases to the bones are rare; less than one per cent of all neoplasms metastases to the maxillofacial area. We describe four cases of metastatic tumours to the jaws. Two cases originated from the thyroid gland while the rest were from the oesophagus and the liver respectively. Three lesions occurred in the mandible and one in the maxilla. Patients presented with oral discomforts disregarding the primary tumor. Physicians who frequently advise patients with oral complaints should keep in mind that whereas these symptoms are mostly of a chronic and benign nature, metastases from a malignant tumor must be included in the differential diagnosis.

Primary MALT lymphomas of the stomach: a pathological study of 18 cases.

AIM: It is doubtful that whoever is suffering from gastric malt lymphoma will escape from the disease, if treated with medication against helicobacter pylori. MATERIAL AND METHODS: A cohort of 18 patients was analysed. Ten hosts had primary gastric malt lymphoma and were treated with gastric resection as the initial therapy. Eight hosts received antibiotics against Helicobacter pylori as the initial treatment. In all 18 patients Helicobacter pylori status, endoscopic findings and pathology features were evaluated. Immunohistochemistry was performed to assess the bcl-2 and p53 status. RESULTS: Patients with low grade malt lymphoma: a) were Helicobacter pylori positive (5 of 5); b) had a superficial lesion (5 of 5); c) had no lymph node involvement (5 of 5); and d) were downstaged by comparison to patients with high grade tumor. Bcl-2 was positive in 4 of 5 low grade tumors, and p53 was positive in 12 of 13 high grade ones. Investigation of patients with 5-year follow up (n = 18) revealed that all but one low-grade tumors remained superficial with no progression. These tumors were bcl-2+/p53-, and the one with a bcl-2+/p53+ immunophenotype progressed to an ulcerated low-grade tumor after disappearance of Helicobacter pylori. Complete regression was found in 6 of 8 patients from the non surgically treated group (n = 8) after Helicobacter pylori eradication. These tumors were superficial/low grade/node negative/bcl-2+/p53 inconclusive (n = 2), superficial/low grade/node negative/bcl-2+/p53- (n = 2), and ulcerative/high grade/node negative/bcl-2+/p53- (n = 2). The two persistent tumors were ulcerative/high grade/node negative/bcl-2+/p53+. CONCLUSION: Gastric malt lymphoma Helicobacter pylori+/superficial/low grade/bcl-2+/p53- will disappear after Helicobacter pylori eradication.

Primary combined carcinoid and adenocarcinoma of the ileum associated with transitional carcinoma of the bladder. Single case report.

Composite neoplasms, carcinoid and adenocarcinoma have been reported to occur in several parts of the body, including the stomach, ampulla of Vater, large bowel, lung, and urinary bladder. Here we report a case of a 74-year-old male with a composite carcinoid-adenocarcinoma of the ileum associated with a transitional cell carcinoma of the bladder. The microscopical examination of the composite tumor showed an admixture of typical carcinoid tumor and moderately a differentiated adenocarcinoma. Immunohistochemically, the two components showed clear-cut differentiations. A review of the literature revealed that this is the first reported case of composite carcinoid-adenocarcinoma of the ileum associated with transitional cell carcinoma of the urinary bladder.

Concurrent low grade B-cell non-Hodgkin's lymphoma of MALT type arising in the large intestine, small intestine and stomach.

Low-grade non-Hodgkin's lymphomas (NHL) of mucosa associated lymphoid tissue (MALT) are indolent neoplasms that, although tending to remain localized for many years, may spread to other mucosal sites. Despite increasing identification of concurrent gastric and intestinal lymphoma of MALT type, the clonal relationship between the tumors and their sequential development are poorly understood. It is also unknown whether the development of these concurrent tumors is closely associated with direct antigen stimulation, which is thought to play an important role in the clonal expansion of low grade MALT lymphomas. The most important function of B-cells is production of specific antibodies. This is largely achieved during B-cell development by recombination of the Ig heavy chain variable (V), diversity (D), and joining (J) segments and hypermutation of the rearranged gene. The rearranged Ig genes of a mature B-cell record much of its evolution history. We report a case of synchronous development of intestinal and gastric low grade MALT lymphomas in a 70 years old female and discuss their possible clonal relationship and sequential appearance.

A stromal myoid cell line provokes thymic T-cell immigration at the second and third gestational trimesters.

UNLABELLED: Once lymphoid precursors enter the thymus form the blood stream, they come into contact with thymic stromal cells that guide their maturation into functionally competent T cells. Thymic myoid cells are one such cell type. They have been described as a regular constituent of the thymus of embryonic and young vertebrates and express muscle proteins including myosin, desmin, acetylcholine receptor (AChR), C-protein, MyoD, troponin T, rapsyn, and utrophin. It has been emphasized recently that the thymic myoid cells play an important role in the protection of thymocytes from apoptosis, and in the process of T-cell differentiation and maturation. AIM: To provide a quantitative estimation of thymic myoid cells and T-cell population in different stages of development. A probable interaction between these two populations could explain an additional mechanism to the active T-cell migration from the thymus that is a direct contact to a specific myoid cell line. MATERIALS AND METHODS: Paraffin-embedded specimens from the thymus of forty five human embryos at the first, second and third trimester of gestation respectively, were investigated by conventional histology, and immunohistology for the presence in the stroma of the thymic medulla, of myosin in the myoid cells, and UCHL1 (pan T-cell) antigen in the medullary thymocytes. RESULTS: Our results demonstrated a quantitative difference in the second and third trimester of development concerning the expression of myosin in the stromal myoid cells of the thymic medulla over the equivalent expression of the protein in the first trimester. Similar changes in the above periods were found concerning the population of medullary thymocytes expressing UCHL1 antigen. CONCLUSIONS: Our results indicate that: (1) Thymic myoid cells play an important role in the thymic microenvironment as they are well conserved throughout species evolution. (2) The increased population of myoid cells in the medullary area during mid and late gestational age, in comparison with first trimester, probably reflects the increased demand of the growing fetus for mature T lymphocytes. Contractions of myoid cells mediated by their cytoplasmic structural proteins, including myosin which is well preserved during development, might aid the movement of thymocytes expressing UCHL1 antigen, across or out of the gland, suggesting a potential involvement of myoid cells in the thymic function. Further studies on larger series are needed to corroborate this.

Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner.

Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1 receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.