Prognostic Significance of p27, Ki-67, and Topoisomerase lla Expression in Clinically Nonfunctioning Pancreatic Endocrine Tumors

Nonfunctioning islet cell tumors or pancreatic endocrine tumors are the most common type of malignant islet cell tumor. Although previously detected usually at an advanced stage because of mass effect, the early detection rate of small localized disease has been increasing. To date it has been difficult to predict the clinical behavior in localized regional nonfunctioning tumors. To investigate potential markers predicting malignancy and poor prognosis in nonfunctioning pancreatic endocrine tumors, we analyzed the expression of Ki-67, topoisomerase IIα (Topollα), and p27, as well as a variety of clinicopathologic parameters in 76 cases of nonfunctioning islet cell tumors (23 benign cases and 53 malignant cases). Ki-67, Topollα, and p27 labeling indices were significantly different between benign and malignant tumors. Expression of Ki-67, Topollα, and p27 were associated with survival in patients with a malignant tumor in a univariate setting. However, only p27 and Topollα were jointly associated with survival in multivariate analysis. Immunohistochemical staining for p27, Topollα, and Ki-67 can be helpful in the diagnosis of nonfunctioning pancreatic endocrine tumor. Analysis of p27 and Topollα may also have potential utility as prognostic factors for malignant tumors.     

Age-associated endocrine dysfunctions and approaches to their correction

This review discusses age-specific functional changes in different components of the endocrine system (pituitary, epiphysis, adrenals, and gonads), their role in aging and age-specific diseases, and possible approaches to correction of endocrine disorders and prevention of accelerated aging.     

Construction of radiation-reduced hybrids and their use in mapping of microclones from chromosome 10p11.2-q11.2

Summary Radiation-reduced hybrids for mapping of DNA markers in the pericentromeric region of chromosome 10 were developed. A Chinese hamster/human somatic cell hybrid (762-8A) carrying chromosomes 10 and Y as the only human material were exposed to 40,000 rads of irradiation and then rescued by fusion with non-irradiated recipient Chinese hamster cells (GM459). Southern hybridization analyses revealed that 10 of 128 HAT-resistant clones contained human chromosomal fragments corresponding to at least one marker locus betweenFNRB (10p-11.2) andRBP3 (10q11.2). These hybrids were then used to map microdissection clones previously isolated and roughly mapped to this chromosomal region by fluorescencein situ hybridization (FISH). Two of the six microclones studied could be mapped to the proximity of the D10-S102 locus. These radiation hybrids are useful for the construction of refined genetic maps of the pericentromeric region of chromosome 10.     

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.     

Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure

BACKGROUND: There is broad human exposure to bisphenol A (BPA), an estrogenic endocrine-disrupting chemical widely used for the production of plastic products. BPA is reported to affect preimplantation embryos or fetuses and alter their postnatal development at doses typically found in the environment. We measured contamination of BPA in various kinds of human biological fluids by a novel enzyme-linked immunosorbent assay. METHODS: Blood samples were obtained from healthy premenopausal women, women with early and full-term pregnancy, and umbilical cord at full-term delivery. Ovarian follicular fluids obtained during IVF procedures and amniotic fluids obtained at mid-term and full-term pregnancy were also subject to BPA measurements. RESULTS: BPA was present in serum and follicular fluid at approximately 1-2 ng/ml, as well as in fetal serum and full-term amniotic fluid, confirming passage through the placenta. Surprisingly, an approximately 5-fold higher concentration, 8.3 +/- 8.7 ng/ml, was revealed in amniotic fluid at 15-18 weeks gestation, compared with other fluids. CONCLUSION: These results suggest accumulation of BPA in early fetuses and significant exposure during the prenatal period, which must be considered in evaluating the potential for human exposure to endocrine-disrupting chemicals.     

Localization of Hepatocyte Growth Factor and Its Receptor met in Endocrine Cells and Related Tumors of the Gut and Pancreas: An Immunohistochemical Study

Hepatocyte growth factor (HGF), a stimulator of angiogenesis and cell migration, regulates the growth of a wide variety of cells by binding to its high-affinity receptor met and is involved in the growth and aggressiveness of several tumors. In this study we investigated the expression of HGF and met in normal endocrine cells and related neoplasms of the gut and pancreas to verify their possible role in tumor pathogenesis, growth, and aggressiveness. Normal tissues and 60 different endocrine tumors were immunostained using specific antibodies directed against HGF, met, and various hormones. HGF immunoreactivity (IR) was found in antroduodenal G cells, rectal enterochromaffin (EC) cells, and pancreatic A and B cells, whereas met IR was detected in antral EC and G cells, and in pancreatic B cells; 46 of 60 tumors examined were positive for HGF, and they were mainly represented by ECL-, EC-, and L-cell neoplasms. met IR was identified in 50/60 tumors of various phenotypes. HGF and met coexpression was found in 42/60 cases, most of which were represented by EC-cell tumors. HGF/met coexpression was significantly more frequent in ileolonic EC-cell tumors, which in the majority of cases were malignant, than in appendiceal EC-cell tumors, which were all benign. Our results demonstrated, for the first time, that HGF and met are specifically distributed in normal gut and pancreatic endocrine cells and, in addition, suggest that HGF and met may be implicated as autocrine/paracrine factors regulating the growth of gastroenteropancreatic endocrine tumors, mainly of ileocolonic EC-cell carcinoids.     

A re-examination of variation associated with environmentally stressed organisms

Variation is an essential feature of biological systems. Populations adapt to dynamic environments, in part, because of this variation. In this review, we re-examine phenotypic variation, especially in organisms living in polluted environments. A recent goal of ecotoxicology is to understand the sublethal effects of exposure to pollutants, e.g. responses to endocrine-disrupting contaminants. While variation is an inherent quality of organisms, variance is a statistical measure of the variation of a trait. Increased variance has been associated with organisms living at the perimeter of a population's range, introduced into novel environments, or exposed to pollution. Some researchers have proposed increased phenotypic variance in exposed populations as an evolutionary mechanism, and others have suggested its use as a biomarker. While we agree that variance often increases in the exposed population, we also recognize that the opposite phenomenon occurs. That is, variance can decrease from exposure to pollution. Altered variance in the exposed population-leading to heteroscedasticity-could result in erroneous conclusions (Type II errors). We suggest that exposure to endocrine-disrupting contaminants could influence the health of populations in ways that are not always represented by measures of central tendency, and that variance and distribution should also be examined in environmentally stressed wildlife.     

Endocrine functions in hypertensive rats of the NISAG strain exposed to epinephrine

Endocrine functions were investigated in normotensive (Wistar) and hypertensive (NISAG) rats before and on days 3, 7, and 21 after subcutaneous epinephrine administration. Rats of the NISAG strain are characterized by elevated plasma levels of aldosterone and thyroxine and lowered plasma levels of immunoreactive insulin, and their endocrine system develops a much stronger response to a single epinephrine injection than does that of Wistar rats. This is manifested in a still higher aldosterone level, elevated corticosterone and insulin concentrations, and reduced thyroxine content in the plasma. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 495–498, May, 1996     

Small cell carcinoma of the gall-bladder with intestinal metaplastic epithelium

A case of small cell carcinoma of the gall-bladder Is described. lmmunohistochemically, the tumor cells were positive for chromogranin A, synaptophysin and neuronspecific enolase, which suggests that they derived from neuroendocrine cells. The overlying and surroundlng epithelium of the tumor showed intestinal metaplasia including goblet cells, pseudopyloric glands, Paneth's cells, and chromogranin A and synaptophysin-positive endocrine cells. Definite adenocarcinoma was absent. The endocrine cells in the epithellum were more numerous In the vicinity of the tumor. The present case supports the supposition that endocrine cell tumor (including small cell carcinoma) of the gall-bladder may develop from endocrine cells of the intestinal metaplastic lesion.