Study of Epithelial to Mesenchymal Transition in Atypical Fibroxanthoma and Undifferentiated Pleomorphic Sarcoma to Discern an Epithelial Origin.

Atypical fibroxanthoma (AFX) is considered a fibroblastic or myofibroblastic neoplasm probably corresponding to a superficial variant of undifferentiated pleomorphic sarcoma (UPS). However, an epithelial origin has also been postulated. An immunohistochemical study of the epithelial to mesenchymal transition (EMT) phenomenon was performed in a series of 19 AFX and 4 UPS to discern an epithelial origin. A panel of epithelial (cytokeratins AE1-AE3 panel, podoplanin D2-40, and E-cadherin) and EMT (vimentin, Twist, Zeb1, and Snail1) markers were evaluated in both tumoral cells and the adjacent epidermis. Podoplanin and Snail1 were negative in all the samples. Nuclear E-cadherin, Twist, and Zeb1 were detected in most lesions, as previously reported in other sarcomas. In the epidermis, E-cadherin showed a normal membranous pattern and only isolated cells were positive for vimentin. Twist and Zeb1 were mainly negative in the epidermis. None of the immunohistochemical markers mentioned above elicited a conspicuous bridging between the epidermis and the dermis. Our findings suggest that EMT does not play a role in the development of AFX or UPS.

Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus.

OBJECTIVE: Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)-cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability. APPROACH AND RESULTS: NK receptor expression (ie, LILRB1, NKG2A, NKG2C, and killer immunoglobulin-like receptors [KIR]) by peripheral NK and T cells was evaluated in 40 patients with HCMV+ with CAP, including nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non-high-risk CAP had higher %NKG2C+ NK cells (29.5 ± 22.4% versus 16.3 ± 13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002-1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7 ± 17.8% versus 41.8 ± 15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (R(Spearman)=-0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (R(Pearson) = 0.591; P=0.012), consistent with higher subclinical systemic inflammation. The intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those patients with HCMV-induced changes in the peripheral NK- and T-cell compartments. CONCLUSIONS: The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.

Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased. OBJECTIVE: To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis. METHODS: We performed a retrospective study that included 146 cSCC samples (51 primary non-metastatic, 56 primary metastatic, 39 lymphatic metastases). Immunohistochemistry for E-cadherin, Vimentin, Snail, beta-catenin, Twist, Zeb1 and Podoplanin was performed. RESULTS: Loss of membranous E-cadherin was observed in 77% cSCCs, with no differences between MSCC and non-MSCC. Among the transcriptional factors controlling EMT, no significant Snail1 expression was detected. Twist, Zeb1, Vimentin, beta-catenin and Podoplanin were significantly overexpressed in MSCCs. Twist ectopic expression in SCC13 cells induced Zeb1, Vimentin and Podoplanin expression and E-cadherin delocalization. These changes resulted in a scattered migration pattern in vitro. Expression of EMT markers was decreased in the metastases when compared with the corresponding primary tumors. CONCLUSION: These results suggest that a partial EMT, characterized by the expression of Twist but without a total E-cadherin depletion, is involved in the acquisition of invasive traits by cSCC, but the process is downregulated in lymph node metastases.

Cardiac myxoma with glandular differentiation: an immunohistochemical and ultrastructural study.

A case of cardiac myxoma with glandular differentiation is reported. The patient did not have elements of the Carney triad or syndrome. The tumor was mainly composed of characteristic stellate cells in a focally collagenized, myxoid stroma, along with aggregates of glandular-forming epithelial cells, with mucin-containing intra- and intercellular lumina. Ultrastructurally, these gland spaces displayed short, straight microvilli and junctional complexes. The epithelial cells were positive for cytokeratin 7 and negative for cytokeratin 20. Calretinin was positive in the stellate cells and negative in the epithelial component. The potential origin from pluripotent mesenchymal cells or from seeded stem cells is hypothesized for glandular differentiation in myxomas. Further studies are required to unravel the relationship between stellate cells and the diverse heterologous components reported in these tumors.

D2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: a marker of metastatic risk.

BACKGROUND: Approximately 4% of cutaneous squamous cell carcinomas (cSCCs) develop lymphatic metastases. The value of lymphatic endothelial markers to enhance the detection of lymphatic tumor invasion in cSCC has not been assessed previously. OBJECTIVE: We sought to evaluate the use of the antibody D2-40, a podoplanin immunohistochemical marker, to identify tumor lymph vessel invasion in cSCC and to assess its expression in tumor cells. METHODS: This was a retrospective case-control study. A series of 101 cSCC, including 51 cases that developed lymphatic metastatic spread (metastasizing cSCC [MSCC]) and 50 cases that resolved definitely after surgical excision (non-MSCC) were included in the study. Lymph vessel invasion using D2-40 was evaluated on all primary biopsy specimens. The percentage of tumor cells showing D2-40 positivity and intensity scoring were recorded. All the immunohistochemical findings were correlated with the clinicopathological features. RESULTS: Lymph vessel invasion was observed in 8% of non-MSCCs and in 25.5% of MSCCs (P = .031). D2-40 expression was significantly increased, both in intensity (odds ratio 4.42 for intensity ++/+++) and in area (odds ratio 2.29 for area >10%), in MSCC when compared with non-MSCC. Interestingly, almost half (49%) of the MSCC had moderate to intense D2-40 positivity compared with 16% of non-MSCC. D2-40 immunohistochemical expression was increased in tumors with an infiltrative pattern of extension. In the multivariate analysis, histologically poorly differentiated tumors, recurrent lesions, and cSCC showing D2-40 overexpression (in intensity) were significantly associated with lymphatic metastases development (odds ratios 15.67, 14.72, and 6.07, respectively). LIMITATIONS: This was a retrospective study. CONCLUSION: The expression of podoplanin associates with high metastatic risk in cSCC.

Value of p16(INK4a) in the diagnosis of low-grade urothelial carcinoma of the urinary bladder in urinary cytology.

BACKGROUND: The sensitivity of urinary cytology for the diagnosis of urothelial carcinomas is low, particularly in low-grade carcinomas. The UroVysion test is a fluorescent in situ hybridization multiprobe assay that increases the sensitivity of urinary cytology. However, this test is not widely available. P16(INK4a) , a protein involved in cell cycle progression, is overexpressed in urothelial carcinoma. Immunocytochemical expression of p16(INK4a) has been examined in biopsy samples from urothelial carcinomas, but few studies have addressed this protein in urine cytology. METHODS: The authors compared the results of p16(INK4a) immunoreactivity in cytology and biopsy samples from 83 cases, including low-grade urothelial carcinomas, reactive epithelial lesions, and negative cases. RESULTS: p16(INK4a) assessment of in urine cytology samples showed a sensitivity of 66.7% and a specificity of 82.8% in the diagnosis of low-grade urothelial carcinomas. CONCLUSIONS: On the basis of these results, the authors propose that immunocytochemical detection of p16(INK4a) is a reliable tool in urine cytology, both for the diagnosis of low-grade urothelial carcinomas and for follow-up purposes. More retrospective and prospective studies are required to verify these results.

B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen.

Neutrophils use immunoglobulins to clear antigen, but their role in immunoglobulin production is unknown. Here we identified neutrophils around the marginal zone (MZ) of the spleen, a B cell area specialized in T cell-independent immunoglobulin responses to circulating antigen. Neutrophils colonized peri-MZ areas after postnatal mucosal colonization by microbes and enhanced their B cell-helper function after receiving reprogramming signals, including interleukin 10 (IL-10), from splenic sinusoidal endothelial cells. Splenic neutrophils induced immunoglobulin class switching, somatic hypermutation and antibody production by activating MZ B cells through a mechanism that involved the cytokines BAFF, APRIL and IL-21. Neutropenic patients had fewer and hypomutated MZ B cells and a lower abundance of preimmune immunoglobulins to T cell-independent antigens, which indicates that neutrophils generate an innate layer of antimicrobial immunoglobulin defense by interacting with MZ B cells.

Nursing workload predictors in Catalonia (Spain): a home care cohort study

Objective: To identify the characteristics of chronic patients and their environment in order to predictthe nursing workload required 1 year after their inclusion in a home care program.Methods: A longitudinal study was carried out in 72 primary health care teams in Catalonia (Spain)with a 1-year follow-up of 1,068 home care patients over 64 years old. The variables collected fromeach patient included data on health and social status (Charlson and Barthel indexes and the Pfeiffer,Braden and Gijon scales), carer overburden (Zarit scale), hospital admissions, use of emergency services,self-perceived health (SF-12) and the number of health worker visits.Results: Patients received 7.2 (SD 10.4) visits per year from their nurse-in-charge, out of a total of 8.7 (SD13.1) nursing visits per year. Risk factors for receiving more nursing visits at home were male gender(IRR = 1.42, 95%CI: 1.20-1.67), dependency for daily activities (IRR = 1.65, 95%CI: 1.29-2.13), decubitusulcers (IRR = 4.03, 95%CI: 2.27-7.14) and receiving emergency medical care at home (IRR = 1.65, 95%CI:1.31-2.07). In contrast, patients with major cognitive impairment (IRR = 0.78, 95%CI: 0.63-0.98) had alower probability of receiving nursing visits at home.Conclusions: Workload can be predicted by patients’ clinical characteristics. The positive correlation ofworkload with variables related to disease severity and the negative correlation with variables relatedto cognitive impairment show that home care nursing in Catalonia is basically demand-oriented (AU)

Objetivo: Identificar las características basales de los pacientes crónicos y su entorno que predicen la cargade trabajo de enfermería durante el a˜no siguiente a su inclusión en un programa de atención domiciliaria(ATDOM).Métodos: Estudio longitudinal realizado en 72 equipos de atención primaria de salud en Catalu˜na.Seguimiento durante un a˜no de 1068 pacientes de ATDOM mayores de 64 a˜nos de edad. Variables recogidas:nivel de salud y situación social (test de Charlson, Barthel, Pfeiffer, Braden y Gijón); sobrecarga delcuidador (Test de Zarit); ingresos hospitalarios y visitas a urgencias; estado subjetivo de salud (SF-12);visitas de los profesionales de salud.Resultados: Los pacientes recibieron 7,2 (DE: 10,4) visitas anuales de su enfermera habitual. Observamosque tienen más riesgo de recibir visitas de enfermería los pacientes varones (IRR = 1,42, IC95%: 1,20-1,67), con dependencia para las actividades de la vida diaria (IRR = 1,65, IC95%: 1,29-2,13), afectados porúlceras por decúbito (IRR = 4,03, IC95%: 2,27-7,14) y que precisaron servicios de atención de urgencia adomicilio (IRR = 1,65, IC95%: 1,31-2,07). Por otro lado, los pacientes con deterioro cognitivo importantetienen menos probabilidad de recibir visitas de su enfermera (IRR = 0,78, IC95%: 0,63-0,98).Conclusiones: Las características clínicas de los pacientes permiten predecir la carga de trabajo de enfermería.Esta relación positiva de la carga de trabajo con las variables relacionadas con la gravedad de laenfermedad y la relación negativa con el deterioro cognitivo muestra que la enfermería domiciliaria enCataluña está básicamente orientada a la demanda(AU)

Nursing workload predictors in Catalonia (Spain): a home care cohort study.

OBJECTIVE: To identify the characteristics of chronic patients and their environment in order to predict the nursing workload required 1 year after their inclusion in a home care program. METHODS: A longitudinal study was carried out in 72 primary health care teams in Catalonia (Spain) with a 1-year follow-up of 1,068 home care patients over 64 years old. The variables collected from each patient included data on health and social status (Charlson and Barthel indexes and the Pfeiffer, Braden and Gijon scales), carer overburden (Zarit scale), hospital admissions, use of emergency services, self-perceived health (SF-12) and the number of health worker visits. RESULTS: Patients received 7.2 (SD 10.4) visits per year from their nurse-in-charge, out of a total of 8.7 (SD 13.1) nursing visits per year. Risk factors for receiving more nursing visits at home were male gender (IRR=1.42, 95%CI: 1.20-1.67), dependency for daily activities (IRR=1.65, 95%CI: 1.29-2.13), decubitus ulcers (IRR=4.03, 95%CI: 2.27-7.14) and receiving emergency medical care at home (IRR=1.65, 95%CI: 1.31-2.07). In contrast, patients with major cognitive impairment (IRR=0.78, 95%CI: 0.63-0.98) had a lower probability of receiving nursing visits at home. CONCLUSIONS: Workload can be predicted by patients' clinical characteristics. The positive correlation of workload with variables related to disease severity and the negative correlation with variables related to cognitive impairment show that home care nursing in Catalonia is basically demand-oriented.

CDC28 protein kinase regulatory subunit 1B (CKS1B) expression and genetic status analysis in oral squamous cell carcinoma.

CKS1B is a member of the highly conserved cyclin kinase subunit 1 (CKS1) protein family which interacts with cyclin-dependent kinases and plays a critical role in cell cycle progression. In oral squamous cell carcinoma (OSCC), as in other malignancies, CKS1B overexpression has been correlated with reduced survival. To our knowledge, no studies evaluating the genetic status of CKS1B gene in OSCC have been reported. Herein, genetic and protein status of CKS1B were analyzed by immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) techniques in a series of primary OSCC (n=51) and lymph node OSCC metastases samples (n=14). The observed results were compared with those obtained in either inflammatory (oral lichen planus [OLP]) (n=13) and premalignant oral mucosal lesions (oral leukoplakia) (n=16). A significant CKS1B overexpression was observed in OSCC and lymph node metastases samples than in OLP and oral leukoplakia (mean 70% vs 35%, p<0.001). CKS1B overexpression correlated with p27 loss of expression (p=0.0013) and SKP2 overexpression (p<0.00). FISH study disclosed statistical differences in both gene amplifications and gains between samples corresponding to OSCC and metastases from those of OLP and leukoplakia (p<0.001). Amplifications were present in 53% of OSCC samples and 33% of lymph node metastases vs 14% of oral leukoplakia and 0% of OLP biopsy specimens (p=0.002). Polysomies of chromosome 1 were seen in 46% of OSCC, 33% of ganglionar metastases, 14% of oral leukoplakia and 10% of OLP (p=0.036). Correlation of CKS1B over-expression and gains (both polysomies and amplifications) determined by FISH was statistically significant (p<0.001). Our results indicate that a high CKS1B expression is a common finding in primary OSCC which correlates with p27 low expression and SKP2 overexpression. This phenomenon may be due either to numerical (chromosome 1 polysomy) or structural (amplifications) CKS1B genetic abnormalities. This phenotypical and cytogenetic profile is not observed in premalignant or inflammatory oral mucosal lesions.

Expression of estrogen and progesterone receptors in the anal canal of women according to age and menopause.

PURPOSE: Fecal incontinence is highly prevalent, especially in menopausal women. The aim of this study was to analyze the expression of estrogen and progesterone receptors in the anal canal of women in relation to menopausal status and age. METHODS: Samples of hemorrhoidal tissue were obtained from 34 women undergoing hemorrhoidectomy. The patients were divided into 2 groups: group 1 consisted of women with a menstrual cycle (n = 17) and group 2 consisted of postmenopausal women (n = 17). Immunostaining of hormone receptors was performed using specific antibodies (DAKO, Copenhagen, Denmark) in cells from the internal anal sphincter, the vascular epithelium, and the squamous epithelium. The percentage of positivity of receptors and the association between age and receptor positivity were compared between the 2 groups. RESULTS: Estrogen receptors were found in the internal anal sphincter in 23.5% in group 1 vs 11.8% in group 2 (P = .656). Progesterone receptors were found in 41.2% in group 1 vs 11.8% of group 2 (P = .118). Squamous epithelium showed estrogen receptors in 52.9% in group 1 vs 64.7% of group 2 (P = .388) and progesterone receptors in 17.6% and 0% in groups 1 and 2, respectively (P = .227). Vascular endothelium showed no receptors. Receptor positivity was not associated with age. CONCLUSION: No significant differences were found in the detection of estrogen and progesterone receptors in structures of the anal canal in women in relation to menopausal status and age.

Síndrome de Meigs y peritonitis esclerosante: una asociación poco frecuente / Meigs’ syndrome and sclerosing peritonitis: an uncommon association

Los tecomas ováricos son tumores estromales relativamente frecuentes que ocasionalmente pueden asociarse con derrame pleural. Los tecomas pueden presentar focos de luteinización y en estos casos se pueden asociar a peritonitis esclerosante. Esta entidad es muy poco frecuente, presenta características histopatológicas propias y clínica heterogénea. Se presenta el caso de una mujer posmenopáusica con dificultad respiratoria y un tumor anexial con sospecha clínica de cáncer ovárico metastásico cuyo estudio anatomopatológico evidenció un tecoma luteinizante con peritonitis esclerosante. Debido a la asociación de una masa ovárica junto a las manifestaciones clínicas que causaba la peritonitis esclerosante es relativamente usual que el diagnóstico de presunción sea de tumor maligno. Todo ello hace importante conocer la entidad, cuya fisiopatología y tratamiento no están consensuados (AU)

Ovarian thecomas are relatively frequent stromal tumors that can occasionally be associated with pleural effusion. Thecomas may contain luteinized foci, and in these cases, can be associated with sclerosing peritonitis. This is a rare, clinically diverse, entity, with its own histopathologic features. We report the case of a postmenopausal woman with respiratory symptoms, bilateral adnexal tumors and suspected metastasizing ovarian cancer, which histopathological study revealed to be a luteinized thecoma associated with sclerosing peritonitis. Due to the clinical manifestations derived from the sclerosing peritonitis and the abdominal mass, a presumptive diagnosis of malignant tumor is quite common. Familiarity with this entity is therefore important. There is no consensus on its physiopathology and treatment (AU)

CKS1B amplification is a frequent event in cutaneous squamous cell carcinoma with aggressive clinical behaviour.

Genetic mechanisms giving rise to the development of cutaneous squamous cell carcinoma (cSCC) are poorly understood and development of genomic high resolution techniques has led to a better knowledge of the genetic basis of several human cancers. In this study, 16 cSCC were analyzed using array comparative genomic hybridization (arrayCGH). The most common aberrations found were gains of 3q11q13, 1q21.3q25, 13q34, and 19p13, and losses of 1p36p31, 3p24p21, 10p15q22, and 13q11q21. We detected gains (3/16) and amplification (1/16) of the 1q21.1q21.3 region. A potential candidate gene in this region, CKS1B (1q21.2), was selected for validation in an independent cohort and correlations with clinicopathological features were carried out. CKS1B gene and protein status were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a series of 53 cSCC, 22 actinic keratoses (AK), and 10 normal skin samples. cSCC presented a higher frequency of chromosome 1 polysomy than AK (70% vs. 46%, P = 0.047). Association between CKS1B protein overexpression and both polysomy and amplification was demonstrated in cSCC (P < 0.001). Regarding amplifications, 11 cSCC patients (21%) presented CKS1B gene amplification. Interestingly, 8/11 (73%) patients who showed a CKS1B amplification had presented metastatic spread (mcSCC). Differences between the presence of CKS1B amplification and the presence or absence of mcSCC were observed (mcSCC [8/14] vs. cSCC [3/39]) (P < 0.001). Several drugs targeting CKS1B have been reported and may be useful for treating patients with cSCC and CKS1B amplifications.

Granulomatosis linfomatoide con presentación neurológica. A propósito de un caso y revisión de la literatura / Lymphomatoid granulomatosis with a neurological presentation. Case report and a review of the literature

La granulomatosis linfomatoide es un tipo poco frecuente de linfoma de célula B grande de afectación extranodal con un crecimiento angiocéntrico y angiodestructivo característico. En una cuarta parte de los casos se asocia a afectación cerebral, pudiendo dar lugar a una constelación de síntomas, si bien lo más frecuente es que se presente en forma de accidente cerebral vascular (AVC). Cuando la enfermedad se presenta únicamente con afectación cerebral y de forma catastrófica, llegar al diagnóstico de esta entidad resulta altamente complicado, siendo prácticamente imposible sin el estudio autópsico(AU)

Lymphomatoid granulomatosis is a rare form of EBV related large B-cell lymphoma, with an angiocentric and angiodestructive growth pattern in extranodal sites. Brain involvement is relatively frequently found, but not as the initial and unique clinical manifestation. When it occurs, brain stroke is the most frequent clinical picture. Moreover, in that setting, patient can die without a definitive diagnosis, and autopsy is then required for a definitive diagnosis purpose(AU)

Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas.

Epidermal growth factor receptor (EGFR) gene amplification and protein overexpression are common in several cancers. EGFR status has seldom been studied in cutaneous squamous carcinomas (SCCs), or their precursors, actinic keratoses (AKs). We evaluated the presence of EGFR genomic aberrations and EGFR protein overexpression in 25 AKs and 35 invasive SCCs by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. EGFR numerical aberrations were detected in 52% of AKs and 77.1% of SCCs (P = 0.042). EGFR amplification was identified in 12% of AKs and 20% of SCCs. No differences regarding EGFR numerical aberrations were observed when AKs with high-grade dysplasia were compared with SCCs. A good correlation was observed between EGFR numerical aberrations and EGFR overexpression. Our results suggest that EGFR numerical aberrations occur in the early stages of epithelial carcinogenesis in skin, not playing a role in the progression from low-grade SCCs into more aggressive phenotypes.

Analysis of gene status in cervical dysplastic lesions and squamous cell carcinoma using tissue microarrays.

Cervical displasia are classified as CIN-I, CIN-II and CIN-III. It has been observed that in at least 60% of CIN-I and CIN-II, the pathology disappears spontaneously, while around 30% persist at 24 months, 10% progress to CIN-III and 1% develops as a SCC. The factors involved in the evolution of the pathology are not defined, although infection of HPV is a necessary condition, but not the only one. For this reason, the identification of genetic changes is an essential element for understanding the carcinogenic process. It can also serve as a helpful tool for identifying patients who may be susceptible to its evolution and treatment, from patients whose lesions could regress spontaneous and for whom periodic follow-ups would be enough. Fifty three cervical biopsies from patients with dysplasia and ISCC were included in the study. These biopsies were set into nine macroarrays. Eight genes and five proteins were examined in each samples (hTERT, PIK3CA, hTERC, MYC, CCND1, BCL2, ZNF217 and p16) by fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC). The results reflected that the genetic alterations of PIK3CA, ZNF217 and CCND1 were associated with the evolution of normal tissue to CIN I, those of hTERC and ERBB with the evolution of LSIL to HSIL, those of hTERT and MYC with the evolution of CIN-II/CIN-III to ISCC, and those of BCL-2 with the inception of ISCC. With regards to proteins, the expression of MYC and CCND1 in the initial stages of the illness would help in the acquisition of the altered cellular phenotype.

Snail1 protein in the stroma as a new putative prognosis marker for colon tumours.

Over-expression of Snail1 gene transcriptional repressor promotes an epithelial-to-mesenchymal transition in epithelial tumour cell lines. Expression of Snail1 RNA has been associated to the pathogenesis of a number of malignancies; however, the lack of good monoclonal antibodies against this protein has precluded a definitive analysis of Snail1 protein. In this study, we aimed to determine the expression of this transcriptional factor in colorectal tumours. Using a Snail1 well-characterized monoclonal antibody developed in our laboratories we have analyzed by immunohistochemistry a cohort of 162 human colorectal tumours. Ninety tumours (56%) showed nuclear expression in the tumoral tissue and the adjacent stroma; in 34 (21%), Snail1 was detected just in the stroma, whereas in only 4 the expression of Snail1 was detected in the tumoral tissue and the stroma was negative. No correlation was found between the presence of Snail1 in the tumour and tumour stage; however, a trend (p = 0.054) was detected when the expression of this factor in the stroma was considered. Snail1 immunoreactivity in this compartment was associated with presence of distant metastasis (p = 0.006). Moreover, expression of Snail1 in the tumor stroma correlated with lower specific survival of cancer patients (p = 0.011). Interestingly, this correlation was also detected in stage I and II tumors. Therefore, our results indicate that the presence of nuclear Snail1 immunoreactive cells in the stroma may be an informative indicator of prognosis of colon tumours especially useful in those corresponding to lower stages and identify a new marker suitable to label activated stroma in colon tumours.

Immunolocalization of androgen receptors, estrogen alpha receptors, and estrogen beta receptors in experimentally induced canine prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an age-dependent prostatic disease affecting male humans and dogs. In dogs, the combined administration of estrogens and androgens synergistically increases prostate weight, and continued treatment leads to the development of glandular hyperplasia. The aim of the present study was to examine the immunohistochemical expression of androgen receptor (AR), estrogen receptor alpha (ER alpha), and estrogen receptor beta (ER beta) in the different cell types of the prostate gland in an experimental model. Five male beagle dogs were castrated and treated with 25 mg of 5 alpha-androstane-3 alpha and 17beta-diol and 0.25 mg 17beta-estradiol for 30 weeks. Prostate specimens were surgically obtained every 45 days (experimental stages M0 to M6: 0, 12, 18, 24, 30, and 36 weeks from the beginning of the hormonal treatment). The control group consisted of 3 noncastrated dogs treated with a vehicle, from which specimens were only taken at the time points M0, M1, M4, and M6. Immunohistochemical data revealed high AR and ER alpha expression in the epithelial and stromal cell nuclei of all the experimental and control specimens. Weak staining of the cytoplasm was observed only in epithelial cells. The suspension of hormone treatment led to a significant reduction in the expression of both receptors. On the contrary, ER beta was expressed only in epithelial cell nuclei, with no significant differences in the percentages of stained nuclei between control and hormonally treated or atrophic prostates. Results indicate that AR, ER alpha, and ER beta are differently expressed in canine prostate tissue and that they show specific expression patterns in response to the hormonal induction of BPH.

Could the truncated variant of ERBB2 be present in the squamous carcinomas of the cervix?

ERBB2, a ligand-less membrane receptor, is frequently overexpressed in a number of human tumors, contributing to uncontrolled cell proliferation. In some cases, gene amplification correlates with protein overexpression and predicts response to trastuzumab. We analyzed the expression of ERBB2 in a group of 40 patients diagnosed with infiltrating squamous cervical carcinomas (ISCC) using a microarray. Immunochemistry was performed using two different antibodies, one against the extramembrane domain and the other one for the intramembrane domain. Ten of the 40 cases included in the study could not be evaluated. Of the 30 remaining biopsies, 13 (42%) showed immunoreactivity only with the antibody against the intramembrane domain. In 5 (16.12%), both intramembrane and extramembrane immunoreactivity was observed, and 12 (40%) were negative for both antibodies. Looking at our results, we propose that, in some ISCC, there is a rupture of the ERBB2 receptor, and this event, with slight genetic amplification, could explain the unfavorable response to trastuzumab observed in some ISCC descript for some authors.

[Do nurses utilize the scientific method?]. / Utilizan las enfermeras el método científico?

The authors wanted to discover the utilization of the Process of Nursing Attention and the NANDA Diagnoses, as well as the main reasons why these methods are or are not put to use. The authors conclude that the non-use of these methods is due to their difficult and complicated language.