Histology and histopathology Vol.27, nº 4 (2012)
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- PublicationOpen AccessExpression of the carbohydrate tumour marker Sialyl Lewis A, Sialyl Lewis X, Lewis Y and Thomsen-Friedenreich Antigen in normal squamous epithelium of the uterine cervix, cervical dysplasia and cervical cancer(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Engelstaedter, V.; Fluegel, B.; Kunze, S.; Mayr, D.; Friese, K.; Jeschke, U.; Bergauer, F.The carbohydrate molecules Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA), Lewis Y (LeY) and Thomsen-Friedenreich antigen (TF) are known to mediate the adhesion between tumor cells and endothelium. They are used as serum markers in diagnosis and treatment in a broad spectrum of human carcinomas, but their expression profile and role in the development of cervical cancer remains unclear. The aim of this study was to investigate the expression of SLeX, SLeA, LeY and TF in normal cervical squamous epithelium, cervical dysplasia and cervical cancer. Slides of paraffin-embedded tissue were fixed and incubated with monoclonal antibodies against SLeX, SLeA, LeY and TF. Immunohistochemical staining was evaluated by using a semi-quantitative score (IRS Score). We found a significant difference of SLeA expression in invasive cervical cancer compared to normal epithelium (p=0.006) and all grades of dysplasia (p=0.002). The expression of SLeX in normal epithelium was less intense than in carcinoma in situ (p=0.036). Staining for LeY showed the weakest results of the investigated markers. Significant differences were found when normal epithelium was compared to CIN I (p=0.011), to CIN II (p=0.013) and to invasive cervical cancer (p=0.005). For TF, significant differences were found in normal epithelium compared to CIN I (p=0.011), CIN II (p=0.013) and compared to invasive cervical cancer (p=0.005). This is the first study on the expression of SLeA, SLeX, LeY and TF in normal cervical endothelium, cervical dysplasia, carcinoma in situ and invasive cervical cancer. Further studies and higher numbers are desirable
- PublicationOpen AccessHistological and immunohistochemical assessment of liver biopsies in morbidly obese patients(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Caballero, T.; Gila, A.; Sánchez Salgado, G.; Muñoz de Rueda, P.; León, J.; Delgado, S.; Muñoz, J.A.; Caba Molina, M.; Carazo, A.; Ruiz Extremera, A.; Salmerón, J.Aims: To study liver lesions in morbidly obese patients who underwent liver biopsy at the time of bariatric surgery to define histological lesions, especially inflammatory infiltrate, diagnostic categories and the possible influence of gender in this respect. Methods and results: 110 biopsies (36 males-M- and 76 females -F-) were evaluated and categorised, according to the NAS (NAFLD -non alcoholic fatty liver disease- Activity Score) system and other criteria, as non-NAFLD (15.5%, F predominance), non-alcoholic steatohepatitis (NASH) (16.5%, M predominance), non-alcoholic hepatosteatosis (NAHS) (21%, F predominance) and, the most numerous group, NASH-borderline (NASH-BORD) (47%), with three subgroups, characterised by centrozonal lesions, portal area preferential involvement or affecting both areas. The predominant form of hepatocytesteatosis was mixed with a multivesicular component that was present in most cases with fibroinflammatory portal involvement. Nuclear glycogenosomes were found in greater number of biopsies in patients in the third and sixth decades. Portal inflammation was present in a large number of cases (M predominance); the application of immunohistochemical techniques (myeloperoxidase and CD68 antibodies) to evaluate lobular inflammation revealed “surgical hepatitis” in one third of the cases, and the presence of microgranulomas (CD68+) (M predominance), which were more abundant with increasing lesion severity. Conclusions: Portal inflammation and multivesicular hepatocytesteatosis are highly prevalent in morbidly obese patients. This study identifies a new subtype of NASH-BORD characterized by centrizonal and porto-periportal area involvement and the existence of liver biopsies without steatosis. CD68+ microgranulomas constitute an unequivocal marker of lobular inflammation in surgical biopsies and of lesion severity, which is gender-related
- PublicationOpen AccessDesmosomes in verrucous carcinoma of the head and neck(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Odar, Katarina; Zidar, Nina; Bonin, Serena; Gale, Nina; Cardesa, Antonio; Stanta, GiorgioVerrucous carcinoma (VC) is a variant of squamous cell carcinoma (SCC), characterised by its inability to metastasize. In contrast, hybrid carcinomas, composed of VC and foci of conventional SCC, harbour a metastatic potential. Correct pathohistological diagnosis is therefore crucial for the choice of treatment. There is mounting evidence that desmosomes are involved in several aspects of carcinogenesis. Previous studies have shown an altered expression of desmosomal components in conventional SCC, which was associated with tumour behaviour, but no data have been found on desmosomes in VC. We therefore analysed the expression of desmosomal components in biopsy samples of 21 cases of VC and 5 cases of hybrid carcinoma of the head and neck in comparison to 23 cases of conventional SCC and 47 samples of normal squamous epithelium of similar localisation, using immunohistochemistry and real-time reverse-transcription polymerase chain reaction. We found that the expression patterns of desmosomal components in VC were fairly similar to those in normal epithelium but differed significantly from those in conventional SCC. Immunohistochemical reactions against desmosomal components disclosed the foci of SCC in hybrid carcinomas. In conclusion, we believe that expression patterns of desmosomal components in VC are consistent with its less aggressive behaviour. Differential expression of desmosomal components between VC and SCC makes some desmosomal components potentially useful in the diagnostics of VC, especially for the detection of hybrid carcinoma
- PublicationOpen AccessTopotecan hydrochloride effects on retinal vessels in newborn rats(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Pescosolido, Nicola; Pascarella, Antonia; Scarsella, Gianfranco; Tafani, Marco; Stefanini, Stefania; Nebbioso, MarcellaA physiological system, i.e. rodent retina during vessel formation and hierarchical organization, was utilised for assaying antiangiogenic properties of Topotecan, a topoisomerase I inhibitor, capable of inhibiting tumoral growth in animal models of retinoblastoma. In particular we analysed possible differences in effectiveness and side effects among different drug dosages and ways of administration. In the present research only qualitative analyses were undertaken. After preliminary experiments, in which suckling animals subcutaneously treated with Topotecan dosages comprised between 9 and 3 mg/kg underwent high lethality and extremely severe systemic damages, 7 day-old rats were subcutaneously, intravenously or peribulbary injected with a single dose of 1 mg/kg; retinal vessels were visualized in retinal fluorangio-graphies taken 1 and 2 weeks after treatment. The most important and frequent alterations were found to affect radial vessels, which showed non-perfused and/or regionally mislocated segments, together with abnormal branching and enlargements in retinal periphery; persistence of capillary-free periarteriolar regions, non-vascularised regions and spots of extravascular FITC were also detected. Despite the high individual variability the alterations were substantially similar among the different ways of drug administration, while they appeared milder in 21 day-old rats, with respect to younger ones. The extensive vascular remodelling found after Topotecan administration, besides demonstrating the antiangiogenic properties of this chemioterapic drug, confirms the rodent retina as a highly valuable model system for studying angiogenesis modulation
- PublicationOpen AccessNuclear localization of GLI1 and elevated expression of FOXC2 in breast cancer is associated with the basal-like phenotype(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Li, Yuan; Yang, Wentao; Yang, Qin; Zhou, ShengAberrant sonic hedgehog (SHH)/glioma-associated oncogene (GLI) signaling has been shown in the development of many tumors. The aims of the present study are to determine the expression of two SHH signaling molecules, the glioma-associated oncogene homolog 1 (GLI1) and forkhead box C2 (FOXC2), in invasive breast cancers (IBC), to evaluate their association with clinicopathological parameters, and to determine their prognostic significance in breast cancer patients. Expression of GLI1 and FOXC2 were assessed by immunohistochemical analysis of a tissue microarray containing 262 unselected IBC cases. A statistical analysis was performed to assess the correlation of GLI1 and FOXC2 expression with the patients’ clinicopathological parameters, postoperative survival rate, and molecular subtypes. Immunoreactivity of GLI1 and FOXC2 was observed in 84% and 75% of all breast cancer tissues, respectively. There was a significant correlation between nuclear FOXC2 and GLI1 expressions in these breast cancers, which was associated with estrogen receptor (ER) negativity. Furthermore, there was a significant association between nuclear expression of GLI1 and FOXC2 and a basal-like breast cancer phenotype. Patients with nuclear GLI1 or FOXC2-expressing tumors had a significantly shorter survival time than those without nuclear FOXC2 or GLI1 expression. Multivariate analysis showed that nuclear GLI1 or FOXC2 expression was an independent factor for predicting the prognosis of basal-like breast cancer. In conclusion, there was a significant correlation between expression of nuclear GLI1 or FOXC2 and human breast cancer. More specifically, elevated levels of these proteins were associated with the basal-like breast cancer phenotype and with a poor rate of disease-free survival. These data suggest that GLI1 and FOXC2 are involved in tumorigenesis and that they may be useful as diagnostic and therapeutic targets for human basal-like breast cancers. Additional studies are warranted to better understand the biological significance of GLI1 and FOXC2, to further refine statistics related to patient prognosis, and to optimize treatment of patients with basal-like breast cancer
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