ABSTRACT
A man aged 83 years with vague perirectal symptoms had a delayed diagnosis of Paget's disease of the anus. A lack of thorough digital rectal examination failed to diagnose a mixed adenonueroendocrine tumour of the rectum in a timely matter.
Subject(s)
Adenocarcinoma/pathology , Anus Neoplasms/pathology , Neoplasms, Complex and Mixed/pathology , Neoplasms, Multiple Primary/pathology , Neuroendocrine Tumors/pathology , Paget Disease, Extramammary/pathology , Rectal Neoplasms/pathology , Adenocarcinoma/diagnosis , Aged, 80 and over , Anus Neoplasms/diagnosis , Delayed Diagnosis , Humans , Male , Neoplasms, Complex and Mixed/diagnosis , Neoplasms, Multiple Primary/diagnosis , Neuroendocrine Tumors/diagnosis , Paget Disease, Extramammary/diagnosis , Rectal Neoplasms/diagnosisABSTRACT
Heparan sulfate proteoglycans (HSPGs) are glycosylated extracellular or membrane-associated proteins. Their unbranched heparan sulfate (HS) disaccharide chains interact with many growth factors and receptors, modifying their activity or diffusion. The pattern of HS sulfation can be altered by the enzymes Sulf1 and Sulf2, secreted extracellular 6-O endosulfatases, which remove specific sulfate groups from HS. Modification by Sulf enzymes changes the binding affinity of HS for protein such as ligands and receptors, affecting growth factor gradients and activities. The precise expression of these sulfatases are thought to be necessary for normal development. We have examined the role of the sulf1 gene in trunk development of zebrafish embryos. sulf1 is expressed in the developing trunk musculature and as well as in midline structures such as the notochord, floorplate and hypochord. Knockdown of sulf1 with antisense morpholinos results in poor differentiation of the somitic trunk muscle, loss of the horizontal myoseptum, lack of pigmentation along the mediolateral stripe, and improper migration of the lateral line primordium. sulf1 knockdown results in a decrease in the number of Pax7-expressing dermomyotome cells, particularly along the midline where the horizontal myoseptum develops. It also leads to decreased sdf1/cxcl12 expression along the mediolateral trunk musculature. Both the Pax7 and cxcl12 expression can be restored by inhibition pharmacological inhibition of BMP signaling, which also restores formation of the myoseptum, fast muscle development, and pigmentation patterning. Lateral line migration and neuromast deposition depend on sdf1/cxcl12 and FGF signaling respectively, both of which are disrupted in sulf1 morphants. Pharmacological activation of FGF signaling can rescue the spacing of neuromast deposition in these fish. Together this data indicate that sulf1 plays a crucial role in modulating both BMP and FGF signaling along the developing myoseptum to coordinate the morphogenesis of trunk musculature, associated pigment cells, and lateral line neuromasts.
Subject(s)
Bone Morphogenetic Proteins/metabolism , Signal Transduction , Somites/metabolism , Sulfatases/metabolism , Sulfotransferases/metabolism , Zebrafish Proteins/metabolism , Animals , Animals, Genetically Modified , Body Patterning/genetics , Embryo, Nonmammalian/embryology , Embryo, Nonmammalian/metabolism , Fibroblast Growth Factors/metabolism , Gene Expression Regulation, Developmental , Gene Knockdown Techniques , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Immunohistochemistry , In Situ Hybridization , Microscopy, Confocal , Morphogenesis/genetics , Muscle, Skeletal/embryology , Muscle, Skeletal/metabolism , Somites/embryology , Sulfatases/genetics , Sulfotransferases/genetics , Time-Lapse Imaging , Zebrafish/embryology , Zebrafish/metabolism , Zebrafish Proteins/geneticsABSTRACT
BACKGROUND: Although involvement of the nipple-areola complex (NAC) occurs in a minority of patients with breast cancer, standard skin-sparing mastectomy requires its removal. To assist in patient selection for NAC preservation we evaluated NAC involvement and correlated this with preoperatively available clinical data. METHODS: Patients with invasive breast cancer or ductal carcinoma in situ undergoing mastectomy from 1998 to 2005 were reviewed retrospectively. The NAC had been evaluated with multiple thin sections. Pathologic data including NAC involvement were analyzed. The mammographic tumor distance from the nipple was measured in 2 standard views. RESULTS: There were 302 patients enrolled, of which 10% were noted to have NAC involvement. This correlated negatively with tumor distance from the nipple (P < .05). A logistic regression equation was derived from the data, with NAC involvement as the dependent variable and distance from the nipple as the independent variable. The equation predicted involvement of the NAC when the distance was less than 4.96 cm with a sensitivity of 82% and a negative predictive value of 97%. CONCLUSIONS: A majority of patients are candidates for NAC preservation. The mammographic distance between the tumor and the nipple is independently predictive of NAC involvement and is useful as an equation variable.
