Immunolocalization of beta-catenin in pleomorphic adenomas and carcinomas ex-pleomorphic adenomas of salivary glands.

Beta-catenin plays a central role in cadherin/catenin cell-cell adhesion complex and is involved in cell signaling pathway. Change in beta-catenin distribution has been associated with several human cancers including salivary gland tumors. We studied the immunolocalization of beta-catenin in a series of pleomorphic adenomas (PA) and carcinomas ex-pleomorphic adenomas (Ca ex-PA). Ten samples of PA and ten of Ca ex-PA were evaluated by immunohistochemistry using streptavidin-biotin-peroxidase technique and a monoclonal antibody against beta-catenin (E-5). Cell membrane/cytoplasmic staining of beta-catenin was observed in normal gland parenchyma, PA, and in well-differentiated Ca ex-PA. Cytoplasmic/nuclear beta-catenin staining was observed in poorly differentiated carcinomas and, interestingly, in one case of PA. Our data showed decreased cell membrane beta-catenin expression in higher-grade tumors suggesting that beta-catenin may play an important role in histologic differentiation and transition to malignant phenotype of Ca ex-PA.

Beta-catenin mutations in craniopharyngiomas and pituitary adenomas.

Craniopharyngiomas and pituitary adenomas are both tumors of the hypothalamic and pituitary region, respectively that are frequently associated with endocrine defects either because of direct involvement of hormone producing cells (most pituitary tumors) or because of secondary defects due to disturbance of hypothalamic function (some pituitary tumors and craniopharyngiomas). Some studies suggest that mutant beta-catenin gene cells in craniopharyngiomas and pituitary adenomas contribute to their tumorigenesis. DNA was extracted from 73 cranial tumors and subjected to polymerase chain reaction (PCR) with previously described primers encompassing glycogen synthase kinase-3beta phosphorylation sites of the beta-catenin gene. Sequenced PCR products for possible beta-catenin gene mutations showed a total of 7/43 alterations in adamantinomatous craniopharyngioma-derived DNA samples. Two previously described beta-catenin mutations in codon 33 TCT(Ser) > TGT(Cys) and codon 37 TCT(Ser) > TTT(Phe), whereas three novel mutations in codon 41 ACC(Thr) > ATC(Ile), codon 33 TCT(Ser) > TAT(Tyr) and codon 32 GAC(Asp) > AAC(Asn) were observed. None of the 22 pituitary adenomas and the eight papillary craniopharyngiomas analyzed presented any sequence alterations. These findings demonstrate an association between beta-catenin gene alterations and craniopharyngiomas of the adamantinomatous type. Since this gene product is involved with development, these results suggest that beta-catenin mutations may contribute to the initiation and subsequent growth of congenital craniopharyngiomas.

Subarachnoid anaesthesia in caesarean delivery: effects on alertness.

AIM: Subjects in spinal anaesthesia have been reported to show a decrease in the level of alertness, even when they have not received any sedative drugs. THE AIM: of this study is to verify, in caesarean delivery if the bupivacaine subarachnoid anaesthesia, with or without intrathecal fentanyl dose, produces a sedative effect, to define the entity and to identify the mechanism that most likely causes it. METHODS: The clinical investigation is divided into Part I (non-randomized trial) and Part II (randomized trial) and is set in the University hospital's delivery-unit. Part I: 45 pregnant women were recruited and enrolled in 3 groups: women having natural delivery (n=15), women receiving caesarean delivery with subarachnoid anaesthesia (n=15) and with general anaesthesia (n=15). Self-rating depression scale (SDS), self-rating anxiety scale (SAS), state anxiety inventory (SAI) and trait anxiety inventory (TAI) psychometric tests were patient-completed for pre-delivery anxiety evaluation. Part II: 23 pregnant women undergoing caesarean delivery were single-blind randomized to receive subarachnoid anaesthesia with single 12.75 mg 0.5% hyperbaric bupivacaine (n=10) or with 12.75 microg 0.5% hyperbaric bupivacaine and 15 mg fentanyl (n=13). Bispectral index (BIS), observer's assessment of alertness/sedation (OAA/S) scale, self-sedation visual analogic scale (VAS) and mean arterial pressure (MAP) were perioperatively monitored. RESULTS: Part I: it was found, using SAI, a higher level of state anxiety in the pregnant women undergoing caesarean delivery than those having natural delivery (p<0.05). Part II: pregnant women receiving subarachnoid anaesthesia for caesarean delivery had a decrease of the level of alertness from 10 to 70 min after the execution of lumbar puncture (p<0.05), with a sedative peak from 35 to 45 min (p<0.01), as measured by OAA/S scale and self-sedation VAS but not by BIS. Women who received bupivacaine-fentanyl spinal anaesthesia had a more consistent sedative effect from 35 to 70 min (p<0.05). CONCLUSIONS: Pregnant women undergoing caesarean delivery had a more elevated level of state anxiety, assessed by SAI, as seen in Part I. Subarachnoid anaesthesia in caesarean delivery is associated with a reduction of alertness level. A double mechanism might cause a clinically valuable sedative effect, observed by OAA/S scale and self-sedation VAS: decrease of the afferent spinal inputs and an anxiolytic psychophysiologic effect, induced by good outcome of the birth and mother-baby contact. Intrathecal bupivacaine-fentanyl dose produces a larger alertness decrease than single bupivacaine, because the anaesthetic block density increases. BIS was not a sensitive measure to detect the light sedation occurring in Part II of this study.