Histology and histopathology Vol.25, nº3 (2010)
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- PublicationOpen AccessSurvivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin(Murcia : F. Hernández, 2010) Peroukides, Stavros; Bravou, Vasiliki; Alexopoulos, Alexandros; Varakis, John; Kalofonos, Haralabos; Papadaki, HelenSurvivin, a member of the family of inhibitorof apoptosis proteins, functions as a key regulator ofapoptosis and cell proliferation. Overexpression ofsurvivin has been implicated in several human cancers,including human hepatocellular carcinoma (HCC).Although several factors have been shown in vitrotoupregulate survivin expression in cancer cells, the invivoregulators of survivin in human hepato-carcinogenesis are largely unknown. We studied byimmunohistochemistry the protein expression ofsurvivin in relation to cyclin D1, phosphorylated signaltransducer and activator of transcription 3 (p-STAT3), ß-catenin, E-cadherin and phosphorylated-Akt (p-Akt) in69 cases of HCC and adjacent liver cirrhosis. Survivinwas expressed in 63/69 (91.3%) cases of HCC and in40/47 (85.1%) cases of liver cirrhosis. Survivinlocalization in HCC was exclusively nuclear, whileintense cytoplasmic and low nuclear expression ofsurvivin was observed in cases of cirrhosis. Survivinexpression in HCC correlated significantly with lowgrade tumors, expression of cyclin D1 and p-STAT3.Expression of survivin in liver cirrhosis correlated withdownregulation of E-cadherin expression. There was nosignificant correlation of survivin with ß-catenin or p-Akt in HCC or liver cirrhosis. In conclusion, we showedan association of nuclear survivin with welldifferentiated HCC, as well as with the expression of thecell cycle regulator cyclin D1. Activation of STAT3 andloss of E-cadherin but not ß-catenin or Akt pathwaysseem to be implicated in survivin upregulation in HCCand liver cirrhosis.
- PublicationOpen AccessMCM proteins as diagnostic and prognostic tumor markers in the clinical setting(Murcia : F. Hernández, 2010) Giaginis, constantinos; Vgenopoulou, Stephanie; Vielh, Philippe; Theocharis, StamatiosMinichromosome maintenance (MCM)proteins are essential for the process of DNA replication,functioning as license components for the S-phase ofcell-cycle initiation and further exerting weak helicaseactivity to unwind DNA from its supercoiled state atreplication forks. The requirement for MCM proteins incycling cells and their absence in quiescent onessupports evidence for their potential clinical applicationas cell proliferation markers. In the last few years, asidefrom their utility as cell proliferation markers, theassessment of MCM expression levels in diverse humanmalignancies has been the focus of extensive research inan aim to facilitate tumor diagnosis and prognosis inclinical settings. The present article aims to review theavailable data so far concerning the clinical significanceof MCM protein expression in human neoplasia incomparison to conventional proliferative markers. Areview of the literature revealed that MCM expression isassociated with important clinicopathological parametersfor patient management and also exhibits significantdiagnostic and prognostic value in several malignancies.MCMs are characterized by higher specificity andsensitivity than the conventional proliferative markers,such as Ki-67 and PCNA, and are thus considered asdiagnostic and prognostic tools of greater clinicalsignificance in several types of human malignancy.
- PublicationOpen AccessClinicopathological variables, immunophenotype, chromosome 1p36 loss and tumour recurrence of 247 meningiomas grade I and II(Murcia : F. Hernández, 2010) Ruiz, Juan; Martínez, Armando; Hernández, Susana; Zimman, Horacio; Ferrer, Milagros; Fernández, Cristina; Sáez, Mamen; López-Asenjo, José A.; Sanz Ortega, JuliánThe WHO grading scheme distinguishesbenign (grade I), atypical (grade II) and anaplastic(grade III) meningiomas. Both atypical and anaplasticmeningiomas exhibited an overall increased rate ofrecurrence, but between 15-20% benign meningiomaswill also exhibit an unfavourable clinical course withrecurrence before 10 years despite aggressive surgery.We investigated 247 cases of meningiomas grade I andII. The immunohistochemical expression of 30 differentmolecular biomarkers of cell adhesion molecules, cell-cycle and apoptosis regulators and checkpoints wasanalyzed. We also determined apoptosis by in-situhybridization (APOPDETEK™) and loss ofchromosome 1p36 by FISH. The study revealed astatistically significant co-variation (p<0.05) betweenmeningiomas grade II associated with severalclinicopathological features (Simpson grade of clinicalresection, necrosis, nuclear atypia, macronucleoli,transition to small cell, sheet-like growth, highcellularity), increased expression of several biomarkersof tumour proliferation (Cyclin A, Cyclin E, MIB-1 orMDM2), proteases (Cathepsin D) or cell-adhesion(CD44) and lower expression of progesterone receptorsthan meningiomas grade I. The presence of Psammomabodies or the location at convexity were protectiveprognostic factors for tumour recurrence while highcellularity and early age of onset (<57 year-old) wereindicators of increased recurrence risk. The expressionof COX-2, γ-catenin, Topoisomerase IIa, VEGF andMIB-1 was significantly higher in the cohort of recurrentmeningiomas. Meningiomas with chromosome 1p36 lossshowed a higher recurrence rate (33.3%) than meningiomas with normal chromosome 1p36 (18%).Increased COX-2 expression in recurrent meningiomamay also suggest a putative role of COX-2 inhibitors asa chemopreventive treatment for recurrence.
- PublicationOpen AccessExpression of p53 family members and CD44 in oral squamous cell carcinoma (OSCC) in relation to tumorigenesis(Murcia : F. Hernández, 2010) Bidaud, Pauline; Chasle, Jacques; Sichel, François; Rousseau, Stéphane; Petit, Pascal; Pottier, Didier; Picquenot, Jean Michel; Louis, Marie-Yolande; Lechevrel, MathildeOral squamous cell carcinomas (OSCCs) aredescribed as the result of a multistep tumorigenesisprocess. In order to develop useful diagnosis of pre-malignant lesions, expression of p53 family membersand the cancer stem cell (CSCs) marker, CD44v6, werestudied in histologically normal oral epithelium,precancerous lesions and succeeding invasive OSCCs.p53 was expressed focally in normal epithelium adjacentto tumors, while expression was high in intra-epithelialneoplasia and moderate in OSCC. p63 nuclear stainingwas important in basal and suprabasal layers ofhistologically normal oral mucosa and in immaturecompartments of premalignant lesions and cancer. Inepithelium without neoplasia, intense p73 staining wasobserved in the basal layer, while focal expression waspresent in suprabasal layers. Most immature dysplasticareas showed either high or moderate staining, whereasthose in OSCCs expressed low and moderate p73 levelexpression. CD44v6 was only expressed in poorlydifferentiated areas of epithelium, altered or not. p53,p63 and p73 positive stainings were statistically relatedin intra-epithelial neoplasia to tumours. Analysis ofTP53 mutations in 17% of tumours principally revealedG>A and A>G transitions. No relation was observedbetween this mutational profile and differentimmunostainings. In conclusion, our results support thatimmunostaining of p53 family members might behelpful in diagnosis and monitoring of high-risk pre-malignant lesions of oral epithelium. The combination ofstaining patterns of p63, p73αand CD44v6 enabled us to isolate phenotypic undifferentiated or transientamplifying areas, reflecting the immaturity of the tumourcell lineage. While CD44v6 expression is an interestingmarker of such epithelial cells, it is not specific enoughto be useful alone and other phenotypic markers areneeded.
- PublicationOpen AccessHistological scoring of articular cartilage alone provides an incomplete picture of osteoarthritic disease progression(Murcia : F. Hernández, 2010) Barley, R.D.C.; Bagnal, K.M.; Jomha, N.M.Purpose: To ascertain whether molecularsubcategories of disease progression exist withinestablished histological grades of articular cartilage(AC). Methods: Based on H&E and safranin-O stainingof AC sections obtained from 18 knee arthroplastysurgeries, 30 samples ranging from Mankin ScoringSystem grade 1 through 5 were identified. Immuno-histochemical (IHC) analysis for collagen type II andaggrecan was performed on serial sections of theparaffin-embedded AC samples. Six AC samples fromeach of the five Mankin Scoring System grades wereexamined. Results: Significant IHC differences incollagen type II and aggrecan deposition were seenwithin AC samples from all five histological grades. Therange of IHC differences in collagen type II andaggrecan increased with increasing histological grade. Achange in the pattern of collagen type II deposition wasobserved in MG-3 AC that was consistent with a switchin collagen type II metabolism. Conclusions: IHCstaining of collagen type II and aggrecan can identifydifferences within histological grades of AC that areconsistent with the existence of molecular subcategories.These differences were detectable even within the lowesthistological grades; therefore the use of IHC staining canfurther enhance and refine the scoring of ACdeterioration in early osteoarthritis (OA). Furthermore,the changes seen in the deposition pattern for bothaggrecan and collagen type II suggest that they could beused to monitor key molecular events in OAprogression. These findings also underscore the need forthe development of IHC scoring criteria.
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