Phyto- and trichobezoars as foreign bodies of the gastrointestinal tract.
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Aged↗
Biomedical subjects
N J Agnantis
Publications and source records attributed to N J Agnantis.
Expression of dysadherin and E-cadherin in trophoblastic tissue in normal and abnormal pregnancies.
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Cadherins↗
The enigmatic nature of apocrine breast lesions.
Epithelial cells of fetal breast glandular structures, at the third trimester of pregnancy (28 weeks), produce GCDFP-15, in the absence of specific apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than a result of metaplasia, and it has been demonstrated that it is estrogen-receptor, progesterone-receptor and bcl-2 negative, but androgen-receptor (AR) positive. The significance of AR expression in apocrine epithelium is uncertain. Apocrine epithelium is seen in a wide spectrum of breast entities, ranging from benign lesions to invasive carcinoma. Breast cancer accounts 32% of all cancer cases among women and is the most common type of cancer in women. Little is known about breast carcinogenesis. Widely, it is accepted that breast cancer, like most other type of cancer, is being developed through the accumulation of genetic aberrations. Apocrine epithelium may reflect instability of the breast epithelium, creating an environment favouring further oncogenic alterations. In the last decade, several lines of evidence support the idea that some breast benign epithelial apocrine lesions are clonal lesions and may be considered as truly pre-malignant or precursors of breast carcinoma. Apocrine changes in many cases do not present any diagnostic difficulty; on the other hand, apocrine proliferations with cytologic atypia can be particularly difficult and challenging. The purpose of this study is to collect and highlight the areas of consensus in the literature as well as the controversial areas concerning the apocrine epithelium of the breast.
Animals↗
Clinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors.
Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which are expressed in normal cells during fetal and postnatal life but also in a variety of human neoplasms. MT expression in human tumors has been linked to resistance to anticancer drugs and differentiation and progression in some types of tumors. This study examined the immunohistochemical expression of MTs in benign, borderline and malignant tumors of ovarian surface epithelium and the possible correlations with clinicopathological parameters and survival. A total of 87 cases with diagnosis of ovarian surface epithelial tumors were included. Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14 borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off level > 10% of tumor cells) was clearly associated with malignancy. A statistically significant correlation was found between the expression of MT in cancer cases and benign tumors (p < 0.0001) and cancer cases and borderline tumors p = 0.003. In cancer cases a difference was observed between grade I and III (p = 0.002). There was no correlation of MT overexpression with survival in the small number of ovarian carcinoma patients where it was analysed. MT constitutes a marker that characterizes aggressiveness and a high malignant potential in ovarian epithelial tumors. In diagnostic problems MT may help distinguish between benign, borderline and malignant tumors.
Adolescent↗
Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions.
The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma.
Carcinoma in Situ↗
DCIS histopathology from a historical perspective.
Ductal carcinoma in situ (DCIS) represents a biologically and morphologically heterogeneous disease. It is characterized by a proliferation of presumably epithelial malignant cells confined within the lumens of the mammary ducts, without evidence of invasion beyond the basement membrane into the adjacent breast stroma. With the widespread use of screening mammography, a dramatic change has occurred in the frequency, management and types of DCIS detected. Historically, there has been some confusion regarding the definition of DCIS and the terminology associated with the histological types of DCIS. In this review, DCIS histopathology from a historical point of view is presented.
Breast Neoplasms↗
Involvement of dysadherin and E-cadherin in the development of testicular tumours.
Testicular neoplasms are comprised of a variety of histologically different forms, and their pathogenesis has not been elucidated. Dysadherin is a recently described cell membrane glycoprotein, which has an anticell-cell adhesion function and downregulates E-cadherin. In this study, we examined immunohistochemically the expression of E-cadherin and dysadherin in 120 testicular neoplasms (37 seminomas-26 classic, five spermatocytic and six anaplastic-, 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature and eight immature teratomas and eight non-Hodgkin B-cell lymphomas), clinical stage I. The intensity, the expression pattern and the percentage of neoplastic cell staining was recorded and correlated with the histologic type and vascular/lymphatic invasion. Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas. Dysadherin expression did not correlate with vascular invasion. Increased dysadherin expression was correlated with aberrant E-cadherin expression in most tumours. In 17% of embryonal carcinomas colocalisation of dysadherin and membranous E-cadherin staining was noted. This is the first report on dysadherin expression and its association with E-cadherin in testicular tumours. Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells. In testicular tumours, as in other neoplasms, dysadherin downregulates E-cadherin expression, at least in part.
Adolescent↗
hMSH2 is the most commonly mutated MMR gene in a cohort of Greek HNPCC patients.
Germline mutations in genes encoding proteins involved in DNA mismatch repair are responsible for the autosomal dominantly inherited cancer predisposition syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We describe here analysis of hMLH1 and hMSH2 in nine Greek families referred to our centre for HNPCC. A unique disease-causing mutation has been identified in seven out of nine (78%) families. The types of mutations identified are nonsense (five out of seven) (hMLH1: E557X, R226X; hMSH2: Q158X, R359X and R711X), a 2 bp deletion (hMSH2 1704_1705delAG) and a 2.2 kb Alu-mediated deletion encompassing exon 3 of the hMSH2 gene. The majority of mutations identified in this cohort are found in hMSH2 (77.7%). Furthermore, four of the mutations identified are novel. Finally, a number of novel benign variations were observed in both genes. This is the first report of HNPCC analysis in the Greek population, further underscoring the differences observed in the various geographic populations.
Adaptor Proteins, Signal Transducing↗
The MAPK-AP-1/-Runx2 signalling axes are implicated in chondrosarcoma pathobiology either independently or via up-regulation of VEGF.
AIMS: To investigate whether and how the JNK/ERK-AP-1/-Runx2 signalling pathways and vascular endothelial growth factor (VEGF) are engaged in the pathogenesis of cartilaginous tumours. Chondrosarcoma is the third most common primary skeletal malignancy. Nevertheless, the molecular events underlying its pathogenesis remain elusive. JNK/ERK MAPKs and their downstream effectors, c-Jun and c-Fos (AP-1), are involved in chondroblastic differention/proliferation. These proteins interact with the Runx2 transcription factor, which is also implicated in chondroblast biology. VEGF, a key angiogenic factor, is up-regulated in human chondrosarcomas. METHODS AND RESULTS: Normal cartilage and neoplastic cells from 45 chondrosarcomas and 21 enchondromas were investigated immunohistochemically. We evaluated the cellular levels of JNK2, p-JNK2 (phosphorylated/activated JNK2), its main substrate, c-Jun, pc-Jun (phosphorylated/activated c-Jun) and c-Fos. Moreover, the levels of p-ERK (phosphorylated/activated ERK), Runx2 and VEGF were assessed. Positive immunostaining for all proteins was observed in the majority of the examined chondrosarcomas and in a small fraction of enchondromas. The expression levels of all proteins were positively and significantly correlated with each other. These levels were substantially augmented in high-grade compared with low-grade chondrosarcomas and in low-grade tumours compared with benign enchondromas, implying a potential use as molecular markers for prediction of high-grade neoplasms. CONCLUSIONS: The JNK/ERK-AP-1/-Runx2 signal transduction 'network' is associated with chondroblastic malignant transformation and chondrosarcoma development, either separately or through coordinated induction of VEGF.
Adult↗
Immunohistochemical study of angiogenesis and proliferative activity in epiretinal membranes.
Formation of epiretinal membranes (ERMs) is a serious complication of retinal diseases, the most important being proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In this study, our goal was to (i) calculate the microvessel density (MVD), (ii) evaluate vascular endothelial growth factor (VEGF) expression and (iii) correlate angiogenesis with the proliferative activity as expressed by the expression of Ki67 marker, in both membrane types. We performed immunohistochemistry in 14 PVR and eight PDR membranes, using antibodies against CD34, VEGF, Ki67 and glial fibrillary acidic protein. PDR membranes presented higher average count of microvessels compared with PVR membranes (p = 0.0015). No differences were observed concerning VEGF expression (p = 0.1). The expression of Ki67 was not correlated with microvessel number or VEGF expression. Our study confirms the presence of vascularisation in PDR membranes, as well as the presence of VEGF even in avascular PVR membranes, suggesting that immunoreactivity for VEGF may not be accompanied by angiogenesis.
Cell Proliferation↗
Clinical correlation of bone marrow microvessel density in essential thrombocythemia.
The aim of this study was to investigate the prognostic relevance of angiogenesis expressed as bone marrow microvessel density (MVD) in 40 patients with essential thrombocythemia (ET). Bone marrow MVD was visualized in paraffin tissue sections using immunohistochemical staining for CD34 protein. Increased MVD of bone marrow specimens was not significantly correlated with clinical (sex, age, microvascular disturbances, liver and spleen size, complications, treatment or no before biopsy), laboratory (peripheral blood count), bone marrow histopathological parameters (cellularity, megakaryocyte clumping and reticulin fibrosis) and overall survival. These preliminary findings suggest that angiogenesis has no prognostic value in patients with ET.
Adult↗
FNAC: its role, limitations and perspective in the preoperative diagnosis of breast cancer.
Fine-needle aspiration cytology (FNAC) was first described and performed in 1930. Thirty years later, it gained acceptance first in Europe and about a decade later in North America. The method is generally considered as a rapid, reliable, safe diagnostic tool to distinguish non-neoplastic from neoplastic breast lesions. In developed countries, in the last 20 years, mammographic screening programmes, which have been used extensively, are designed to detect the earliest possible breast cancer. The FNAC report is extremely important because it gives the necessary information for the management of patients, in order to proceed with more invasive diagnostic methods or surgical treatment, and to decide what kind of operation to perform. In the preoperative phase, FNAC has taken a fundamental role of both palpable and nonpalpable lesions, using ultrasound or stereotactic guidance. New developed techniques, breast biopsy instrumentation (ABBI) and mammotome have the advantage of complete removal of breast lesions, but this is not possible in all the examined cases. In developing countries, economical restrictions, low budget for health care and screening programmes put the patients at a disadvantage because of the high cost of sophisticated diagnostic methods, thus we recommend that FNAC be used as a routine diagnostic method because of its low cost compared with the others and this policy maximizes the availability of health care to women with breast cancer. We conclude that FNAC plays an important and essential role in the management of patients with breast lesions and also offers a great potential for prediction of patient outcome, disease response to therapy and assessment of risk of developing breast cancer. The reliability and efficiency of the method depends on the quality of the samples and the experience of the medical staff that performs the aspiration.
Biopsy, Fine-Needle↗
Cell cycle proteins in laryngeal cancer: role in proliferation and prognosis.
A study of laryngeal carcinomas was performed in order to analyze (a) the expression of p53/p21, cyclin D1/cyclin E, p21/p27 (b) the relation of normal and abnormal protein expression, with the proliferation status, as determined by the expression of Ki67 and PCNA and (c) the correlation of our findings with prognosis. We performed a retrospective analysis of 57 cases of squamous cell carcinomas of the larynx. We applied monoclonal antibodies against p53, p21, p27, cyclin D1, cyclin E, Ki67 and PCNA, using streptavidin-biotin method. Analysis of the p53/p21 proteins, revealed abnormalities in 25/37 cases (67.57%), while 12/37 (32.43%) cases displayed normal phenotype (p53-/p21-). Analysis of cyclins revealed overexpression in 17/48 cases (35.42), while the majority 31/48(64.58%) displayed normal phenotype (cyclin D1-/cyclin E-). Concerning CDKIs expression, the majority 30/50(60%) presented high levels of both inhibitors (p21+/p27+). Cases with simultaneous overexpression of CDKIs demonstrated significantly higher levels of Ki67 protein (p = 0.05). Analysis of p53/p21, cyclin D/cyclin E, p21/p27 patterns showed no association between the presence of one or two alterations and prognosis. In conclusion, we demonstrated that p53 tumor suppressor pathway is frequently disrupted in laryngeal cancer. Furthermore, levels of CDKIs, although they act as cell cycle activity blockers, are not reliable markers for the estimation of laryngeal neoplastic cells growth fraction.
Carcinoma, Squamous Cell↗
Immunohistochemical expression of vascular endothelial growth factor correlates with positive surgical margins and recurrence in T1 and T2 squamous cell carcinoma (SCC) of the lower lip.
Tumor angiogenesis is associated with tumor progression and aggressiveness in a number of malignancies, and vascular endothelial growth factor (VEGF) is considered as a leading candidate in this process. The aim of the present study was to investigate the role of VEGF immunohistochemical expression and tumor angiogenesis in predicting local recurrence in surgically treated lip SCC. We performed a retrospective analysis of 50 patients with lip SCC in order to investigate whether VEGF immunohistochemical expression and tumor angiogenesis correlate with clinicopathologic parameters and outcome. Tumor angiogenesis was estimated by determining microvessel density (MVD) with the use of CD34 antibody. Our results showed that VEGF was strongly correlated with tumor invasion towards the surgical margin. There was also a significant association of high VEGF expression with a higher incidence of local recurrence (p < 0.001). We suggest that VEGF expression may be used as an index to distinguish patients with higher risk of relapse.
Adult↗
Mucoepidermoid carcinoma of the thymus: a case presentation and a literature review.
Mucoepidermoid carcinoma of the thymus is an unusual, but well-recognized variant of thymic malignant tumors. Its biologic behavior generally depends on the degree of differentiation and the amount of cellular atypia. High grade tumors can be aggressive neoplasms with a tendency to invade and develop metastases. We report on a case of a 53-year-old man, who presented chest discomfort, dyspnea, and weakness. As heart function tests were normal, the patient underwent radiologic examination, which showed a well-demarcated mass in the anterior mediastinum. Histologic examination of the surgically resected mass showed features of a mucoepidermoid carcinoma with associated infiltration of the pleural tissue. Postoperative radiotherapy and chemotherapy were performed, and the patient died two months after initial diagnosis. In case of the absence of metastatic disease or other common primary neoplasms of the thymus, the diagnosis of a mucoepidermoid thymic carcinoma should be taken into consideration, although this tumor is rare.
Carcinoma, Mucoepidermoid↗
Angiogenesis in chronic myeloproliferative diseases detected by CD34 expression.
Increased bone marrow angiogenesis estimated as bone marrow microvessel density (MVD), or as serum angiogenic factor levels and/or immunohistochemical expression of these factors in bone marrow biopsy has been demonstrated in a variety of hematological disorders including chronic myeloproliferative diseases (MPDs). The aim of this study was to investigate the MVD in 25 cases of myelofibrosis with myeloid metaplasia (MMM). MVD was estimated by CD34 immunohistochemical expression in bone marrow biopsies. A control group of 27 patients without bone marrow disease, eight cases of polycythemia vera (PV), 41 cases of essential thrombocythemia (ET) and nine cases of chronic myeloid leukemia (CML) were also studied. Moreover, in cases with MMM, MVD was correlated with clinical, laboratory, histological parameters and the outcome of the patients. Our study confirmed a significantly higher degree of angiogenesis in MMM, PV, ET and CML compared with controls (P < 0.001, P = 0.0007, P < 0.001 and P = 0.0008, respectively). Angiogenesis was higher in MMM than PV, ET and CML cases (P < 0.001, P < 0.001 and P = 0.008). Increased angiogenesis was correlated with hypercatabolic symptoms in MMM patients (P = 0.009). No correlation with other clinicopathological parameters or clinical outcome was found. However, definitive conclusions regarding the prognostic value of increased angiogenesis may require additional follow-up and a larger group of patients.
Aged↗
Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27(Kip1) in urothelial carcinoma: correlation with other cell-cycle-related proteins (Rb, p53, Ki-67 and PCNA) and clinicopathological features.
INTRODUCTION: The expression pattern of cyclins D1 and E, as well as cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to tumour behaviour and patients' prognosis was examined in 142 urothelial cell carcinomas. The expression of these proteins was also analyzed along with other cell-cycle-related proteins such as: p53, pRb and the proliferation-associated indices Ki-67 and proliferating cell nuclear antigen (PCNA). PATIENTS AND METHODS: These molecule markers were localized immunochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. RESULTS: Focal positivity (<10% of tumour cells) or the absence of cyclin D1 immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1 expression was correlated with tumour grade and stage as well as with the existence of in situ component. In addition, cyclin D1 expression was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score. Focal positivity (<20% of tumour cells) or the absence of cyclin E immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E expression was correlated with tumour stage. A positive relationship between cyclin E expression and the two associated proliferating indices Ki-67 and PCNA, as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%) of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb expression was observed. Absence or focal immunostaining (<20% of tumour cells) of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression was correlated with tumour grade as well as with cyclins D1 and E. The prognostic significance of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression with both univariate (log rank test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. CONCLUSION: These findings suggest that the level of the cell cycle regulators studied does not seem to have a clinical value in terms of predicting the risk of early recurrence and progression. In addition the interrelationship probably means their contribution to the regulation of cell growth through different pathways in bladder carcinogenesis.
Adult↗
Expression of vascular endothelial growth factor (VEGF) and association with microvessel density in small-cell and non-small-cell lung carcinomas.
Recent studies have demonstrated that tumor angiogenesis is a prognostic factor for various malignant neoplasms. Specifically, in non-small-cell lung carcinomas (NSCLCs) most reports show an association between neovascularization and vascular endothelial growth factor (VEGF) expression as well as the presence of metastases and survival, although a few reports do not agree with these findings. Angiogenesis is not clearly characterized in small-cell lung carcinomas (SCLCs), since they are rarely treated by surgery, and thus the available tissue for biological characterization is sparse. The aim of the present study was to investigate angiogenesis and the expression of VEGF in lung tumors. We examined 88 non-small-cell and 39 small-cell lung carcinomas. Angiogenesis was estimated by determining microvessel counts, with the use of anti-CD31 and anti-factor VIII antibodies and expression of VEGF was also evaluated immunohistochemically. Our data showed that in NSCLCs angiogenesis was more prominent in poorly-differentiated neoplasms and correlated with VEGF expression, therefore it is at least in part mediated by the latter. Interestingly, in SCLCs a higher vascularization was noted. However, there was no strong association with VEGF expression. Thus, small-cell lung carcinoma may represent a suitable neoplasm for testing antiangiogenic drugs in combination with chemotherapy. Nevertheless, antiangiogenic therapy should not be targeted specifically to the VEGF pathway, since in SCLCs other mediators of angiogenesis may be important as well.
Aged↗