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Since the identification of NM23 (now called NME1) as the first metastasis suppressor gene (MSG), a small number of other gene products and non-coding RNAs have been identified that suppress specific parameters of the metastatic cascade, yet which have little or no ability to regulate primary tumor initiation or maintenance. MSG can regulate various pathways or cell biological functions such as those controlling mitogen-activated protein kinase pathway mediators, cell–cell and cell-extracellular matrix protein adhesion, cytoskeletal architecture, G-protein-coupled receptors, apoptosis, and transcriptional complexes. One defining facet of this gene class is that their expression is typically downregulated, not mutated, in metastasis, such that any effective therapeutic intervention would involve their re-expression. This review will address the therapeutic targeting of MSG, once thought to be a daunting task only facilitated by ectopically re-expressing MSG in metastatic cells in vivo. Examples will be cited of attempts to identify actionable oncogenic pathways that might suppress the formation or progression of metastases through the re-expression of specific metastasis suppressors. [ABSTRACT FROM AUTHOR]

Introduction: The overdiagnosing of papillary thyroid carcinoma (PTC) in China necessitates the development of an evidence-based diagnosis and prognosis strategy in line with precision medicine. A landscape of PTC in Chinese cohorts is needed to provide comprehensiveness. Methods: 6 paired PTC samples were employed for whole-exome sequencing, RNA sequencing, and data-dependent acquisition mass spectrum analysis. Weighted gene co-expression network analysis and protein-protein interactions networks were used to screen for hub genes. Moreover, we verified the hub genes' diagnostic and prognostic potential using online databases. Logistic regression was employed to construct a diagnostic model, and we evaluated its efficacy and specificity based on TCGA-THCA and GEO datasets. Results: The basic multiomics landscape of PTC among local patients were drawn. The similarities and differences were compared between the Chinese cohort and TCGA-THCA cohorts, including the identification of PNPLA5 as a driver gene in addition to BRAF mutation. Besides, we found 572 differentially expressed genes and 79 differentially expressed proteins. Through integrative analysis, we identified 17 hub genes for prognosis and diagnosis of PTC. Four of these genes, ABR, AHNAK2, GPX1, and TPO, were used to construct a diagnostic model with high accuracy, explicitly targeting PTC (AUC=0.969/0.959 in training/test sets). Discussion: Multiomics analysis of the Chinese cohort demonstrated significant distinctions compared to TCGA-THCA cohorts, highlighting the unique genetic characteristics of Chinese individuals with PTC. The novel biomarkers, holding potential for diagnosis and prognosis of PTC, were identified. Furthermore, these biomarkers provide a valuable tool for precise medicine, especially for immunotherapeutic or nanomedicine based cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: Thyroid cancer recurrence following curative thyroidectomy is associated with increased morbidity and mortality, but current surveillance strategies are inadequate for early detection. Prior studies indicate that tissue glycosylation is altered in thyroid cancer, but the utility of serum glycosylation in thyroid cancer surveillance remains unexplored. We therefore assessed the potential utility of altered serum glycomic profile as a tumor‐specific target for disease surveillance in recurrent thyroid cancer. Experimental design We employed banked serum samples from patients with recurrent thyroid cancer post thyroidectomy and healthy controls. N‐glycans were enzymatically released from serum glycoproteins, labeled via permethylation, and analyzed by MALDI‐TOF mass spectrometry. Global level and specific subtypes of glycan structures were compared between patients and controls. Results: We evaluated 28 independent samples from 13 patients with cancer recurrence and 15 healthy controls. Global features of glycosylation, including N‐glycan class and terminal glycan modifications were similar between groups, but three of 35 individual glycans showed significant differences. The three glycans were biosynthetically related biantennary core fucosylated N‐glycans that only varied by the degree of galactosylation (G0F, G1F, and G2F; G: galactose, F: fucose). The ratio of G0F:G1F that captures reduced galactosylation was observed in patients samples but not in healthy controls (p = 0.004) and predicted thyroid cancer recurrence (AUC = 0.82, CI 95% = 0.64–0.99). Conclusions: Altered N‐glycomic profile was associated with thyroid cancer recurrence. This serum‐based biomarker would be useful as an effective surveillance tool to improve the care and prognosis of thyroid cancer after prospective validation. Cellular transformation is associated with alterations in cell surface carbohydrates or glycans. However, the role of glycosylation in thyroid cancer recurrence remains unexplored. Using N‐glycomics of total patient serum we identified a glycan‐based biomarker that is associated with thyroid cancer recurrence. [ABSTRACT FROM AUTHOR]

Background/Aim: Silicone implants are widely used biomaterials in surgeries owing to their physiological inertness and low toxicity. However, capsular contracture is a severe complication caused by the insertion of breast implants, which can endanger the health of patients. In this study, twelve different silicone breast implants were tested to determine which could lead to a lower incidence of capsular contracture. Materials and Methods: For in vivo experiments, these silicone implants were implanted into 60 rats (i.e., five implants per rat). The implants were explanted eight weeks after the operation. Samples were analyzed and measured by using hematoxylin and eosin staining, Masson's trichrome staining, and immunofluorescence staining methods. We compared twelve samples for their differences in the thickness of capsular formation, number of inflammatory cells, collagen expression, fibroblast intensity (i.e., Vimentin and α-SMA), and inflammatory cytokines (i.e., IL-8, CD68, MCP-1, and F4/80). Results: Different surface textures of breast implants gave different effects on capsular thickness, collagen formation, fibroblast formation, and potential inflammation. Samples that had smooth textures such as SEBBIN, HANS, and Mentor showed higher collagen formation than other samples. SEBBIN Texture, Motiva Micro, HANS Smooth I, and HANS Micro exhibited higher fibroblast formation (i.e., α-SMA, Vimentin). SEBBIN Smooth and samples in HANS group displayed lower expression of inflammation cytokines (IL-8, CD68, MCP-1, and F4/80). Conclusion: These findings provide preliminary reports on the surface texture effect and support a selection of breast silicone implants in breast reconstruction to avoid the formation of capsular contracture after implantation. [ABSTRACT FROM AUTHOR]

Background: Choroid plexus carcinoma (CPC) is a predominately pediatric CNS tumor with a variety of histologic features, with hyaline globules only reported once previously. Case report: A two-year-old male child presented with headaches, vomiting, and lower limb weakness. Radiological examination revealed a right temporoparietal intra-axial tumor. On histology, it showed features of CPC containing multiple eosinophilic intracytoplasmic and extracellular hyaline globular structures, which were PAS-positive, diastase resistant, and immunoreactive for alpha-fetoprotein (AFP). Conclusion: CPC can occasionally show AFP immune-positive hyaline globules. [ABSTRACT FROM AUTHOR]

Background: Capsular contracture is a severe complication to breast surgery with implants. Previous studies suggest multiple risk factors are associated with capsular contracture, but the etiology is still unknown. We performed a literature review to investigate existing studies on histological analyses of breast implant capsules and how clinical risk factors impact the capsule morphology. Methods: The literature search was conducted in PubMed. Studies that performed histological analyses of breast implant capsules were included. Animal studies or studies with a study population of less than five patients were excluded. Results: Fifty-two studies were included. The histological analyses showed that the breast implant capsules were organized in multiple layers with an inner layer of synovial-like metaplasia which was reported to diminish in capsules with capsular contracture. The remaining layers of the capsule mostly consisted of collagen. The alignment of the collagen fibers differed between contracted and non-contracted capsules, and capsules with higher Baker grade were generally thickest and contained more tissue inflammation. Studies investigating capsules affected by radiotherapy found a more pronounced inflammatory response and the capsules were generally thicker and fibrotic compared with nonirradiated capsules. Conclusions: The included studies offer valuable insights into the histological changes caused by capsular contracture and their relation to clinical risk factors. Further studies with larger sample sizes and more strict inclusion criteria are needed to further investigate implant capsules and the role of the synovial-like metaplasia for the development of capsular contracture. Level of Evidence III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Smooth muscle is found around organs in the digestive, respiratory, and reproductive tracts. Cancers arising in the bladder, prostate, stomach, colon, and other sites progress from low-risk disease to high-risk, lethal metastatic disease characterized by tumor invasion into, within, and through the biophysical barrier of smooth muscle. We consider here the unique biophysical properties of smooth muscle and how cohesive clusters of tumor use mechanosensing cell–cell and cell–ECM (extracellular matrix) adhesion receptors to move through a structured muscle and withstand the biophysical forces to reach distant sites. Understanding integrated mechanosensing features within tumor cluster and smooth muscle and potential triggers within adjacent adipose tissue, such as the unique damage-associated molecular pattern protein (DAMP), eNAMPT (extracellular nicotinamide phosphoribosyltransferase), or visfatin, offers an opportunity to prevent the first steps of invasion and metastasis through the structured muscle. [ABSTRACT FROM AUTHOR]

Background: The objective of this clinical review is to provide an overview of the use of silicone gel-filled breast implants placed in the sub-muscular position, with a focus on complication rates reported for both smooth and textured implants. Furthermore, our experience in this field is also reviewed. Methods: MEDLINE, EMBASE, Web of Science, Scopus, the Cochrane Central and Google Scholar databases were reviewed to identify the literature related to smooth breast implants. Each article was reviewed by two independent reviewers to ensure all relevant publications were identified. The literature search identified 98 applicable articles. Of these, just a few articles were found to have a therapeutic level of evidence. The reference lists in each relevant paper were screened manually to include relevant papers not found through the initial search. Results: Eight articles report the risk of capsular contracture when the breast implants were placed in the sub-muscular position. Six of these articles report a similar rate of capsular contracture in smooth and textured implants. Local complications such as wrinkling, late seroma and double capsules were found to be associated with the use of textured breast implants (4 articles). All articles concerning BIA-ALCL reported a total absence occurring in smooth breast implants. All cases have been associated with textured mammary prostheses. Conclusion: With our expertise in the field and the results of this up-to-date literature review, it can be concluded that there are no significant advantages of using one type of implant surface over the other when placed in the sub-pectoral position. Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

The aim of the present study was to describe a case of renal angiomyolipoma (RAML) in a 31-year-old woman who presented with massive hemorrhage, shock, severe anemia (Hb 63 g-l) and multiple lesions, prior to delivery of a dead fetus. A 31-year-old woman was admitted due to left flank and abdominal pain at 20 weeks of gestation age, and diagnosed with RAML complicated with spontaneous rupture and hemorrhage of the left kidney, for which emergency exploratory laparotomy, left kidney resection and splenectomy were performed. The patient delivered a dead fetus 3 days following surgery and recovered well postoperatively. Hemorrhagic RAML during pregnancy is a rare and complex vascular surgical emergency, and should be managed in a multidisciplinary manner. Spontaneous rupture is a serious threat to the life and health of pregnant women and fetuses. The present case is a typical example of RAML in a pregnant woman complicated by spontaneous rupture and hemorrhage, which highlights the importance of determining the risk of acute hemorrhage in early stages of pregnancy, and the significance of time and proper management. However, in cases of shock caused by spontaneous rupture and hemorrhage, the only way to save the life of the patient is to resect the lesion without delay. [ABSTRACT FROM AUTHOR]

Hyaline globules (thanatosomes) have been observed in many neoplastic and non-neoplastic processes. They represent terminal cytoplasmic structures associated with cytoplasmic blebbing, which are related to cell injury and apoptosis. Thanatosomes are reported rarely in breast tumors. Here we describe a case of invasive breast cancer of no special type with abundant thanatosomes. [ABSTRACT FROM AUTHOR]

As much as 5% of prostate biopsies yield findings equivocal for malignancy even for skilled uropathologist; such “grey zone” lesions have been addressed in many ways, although the acronym ASAP (atypical small acinar proliferation) is the most widely used when referring to an atypical focus suspicious, but not diagnostic, for malignancy. Since the introduction of this diagnostic category more than 20 years ago, debate has ensued over its histological characterization and clinical significance. Pathology reporting of ASAP, commonly based on strict morphological criteria and traditional immunohistochemical markers such as basal cell antibodies, has been improved by recent availability of novel immunohistochemical markers such as AMACR and ERG. Further pathological issues, such as the role of pre-analytical variables, number of tissue levels, interobserver variability, and association with prostatic intraepithelial neoplasia also play a role in the optimal assessment of ASAP. Apart from diagnostic issues, a major issue is ASAP predictive value for prostate cancer on repeat biopsy. Therefore, attempts have been made to identify clinical and biological parameters that could predict subsequent diagnosis of malignancy as well as define time and modality of repeat biopsy. Finally, pathological features of cancers detected after a previous ASAP diagnosis are compared with those diagnosed at first prostate biopsy. [ABSTRACT FROM PUBLISHER]

Background: This study investigated the relationships between histomorphological aspects of breast capsules, including capsule thickness, collagen fiber alignment, the presence of α-smooth muscle actin (α-SMA)-positive myofibroblasts, and clinical observations of capsular contracture. Methods: Breast capsule samples were collected at the time of implant removal in patients undergoing breast implant replacement or revision surgery. Capsular contracture was scored preoperatively using the Baker scale. Histological analysis included hematoxylin and eosin staining, quantitative analysis of capsule thickness, collagen fiber alignment, and immunohistochemical evaluation for α-SMA and CD68. Results: Forty-nine samples were harvested from 41 patients. A large variation in histomorphology was observed between samples, including differences in cellularity, fiber density and organization, and overall structure. Baker I capsules were significantly thinner than Baker II, III, and IV capsules. Capsule thickness positively correlated with implantation time for all capsules and for contracted capsules (Baker III and IV). Contracted capsules had significantly greater collagen fiber alignment and α-SMA-positive immunoreactivity than uncontracted capsules (Baker I and II). Capsules from textured implants had significantly less α-SMA-positive immunoreactivity than capsules from smooth implants. Conclusion: The histomorphological diversity observed between the breast capsules highlights the challenges of identifying mechanistic trends in capsular contracture. Our findings support the role of increasing capsule thickness and collagen fiber alignment, and the presence of contractile myofibroblasts in the development of contracture. These changes in capsule structure may be directly related to palpation stiffness considered in the Baker score. Approaches to disrupt these processes may aid in decreasing capsular contracture rates. Level of Evidence III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors . [ABSTRACT FROM AUTHOR]

Background The epithelial-to-mesenchymal transition (EMT) process results in a loss of cell-cell adhesion, increased cell mobility, and is crucial for enabling the metastasis of cancer cells. Recently, the enzyme SIRT1 has been implicated in a variety of physiological processes; however, its role in regulating oral cancer metastasis and EMT is not fully elucidated. Here, we propose a mechanism by which the enzyme sirtuin1 (SIRT1) regulates the EMT process in oral cancer by deacetylating Smad4 and repressing the effect of TGF-β signaling on matrix metalloproteinase-7 (MMP7). Methods The roles of SIRT1 in tumor cell migration/invasion and metastasis to the lungs were investigated using the Boyden chamber assay and orthotopic injections, respectively. RNA interference was used to knockdown either SIRT1 or Smad4 expression in oral squamous cell carcinoma (OSCC) cell lines. Immunoblotting, zymographic assays, and coimmunoprecipitation were used to examine the effects of SIRT1 overexpression on MMP7 expression and activity, as well as on SIRT1/ Smad4 interaction. Results We found that compared with normal human oral keratinocytes (HOKs), SIRT1 was underexpressed in OSCC cells, and also in oral cancer tissues obtained from 14 of 21 OSCC patients compared with expression in their matched normal tissues. Overexpression of SIRT1 inhibited migration of OSCC cells in vitro, as well as their metastasis to the lung in vivo. Furthermore, up-regulation of SIRT1 in metastatic OSCCs significantly inhibited the migration and invasion abilities of OSCC cells, while concomitantly increasing the expression of E-cadherin, and decreasing the expressions of mesenchymal markers. We also identified Smad4, a TGF-β-activated transcription factor, as a direct target protein for SIRT1. Overexpression of SIRT1 in OSCC cells led to decreased levels of acetylated Smad4, and inhibition of TGF-β-induced signaling. By associating and deacetylating Smad4, SIRT1 enzyme can influence MMP7 expression, MMP enzyme activity, and consequently, cell migration, invasion, and tumor metastasis in OSCCs. Conclusions These findings provide a valuable insight into the potential role of the SIRT1 enzyme in regulating cell migration and invasion in oral squamous cell carcinoma. Our findings suggest the SIRT1/Smad4/MMP7 pathway as a target for oral cancer driven by EMT. [ABSTRACT FROM AUTHOR]

Tumor progression is characterized by loss of cell adhesion and increase of invasion and metastasis. E-cadherin, a cell adhesion molecule, is frequently downregulated and has been proposed as an important mediator in epithelial-mesenchymal transition (EMT) in tumors. In this study, we investigated the expression of E-cadherin and its association with cancer invasion and prognosis in cholangiocarcinoma (CCA). Immunohistochemistry results demonstrated a statistically significant association between the positive metastasis status with low E-cadherin protein expression in human CCA tissues ( P = 0.04). Statistical trends were identified for low E-cadherin level and shorter survival time ( P = 0.08). Targeting the E-cadherin expression in CCA cells with siRNA caused upregulation of vimentin, a mesenchymal marker, and disappearance of the E-cadherin/β-catenin adhesion complex from cell membranes. Moreover, migration and invasion abilities of the cells were increased under this condition. These findings suggest that reduction of E-cadherin contributes to CCA progression by attenuating the strength of cellular adhesion, which affects motility as well as regulating the expression of EMT-related genes during CCA invasion and metastasis. Thus, E-cadherin can act as a central modulator of tumor cell phenotype and is a potential metastasis marker in CCA. [ABSTRACT FROM AUTHOR]

Nested/microcystic ( NV/ MV) urothelial carcinoma ( UC) variants are associated with mild cytologic atypia and commonly present at high-stage disease. The histopathogenesis is investigated using urothelial basal cell markers. Archival 14 NV/ MV and three inverted papilloma ( IP) were immunostained for CD44, cytokeratin 5 ( CK5), CK34bE12 and p63. Twenty consecutive cases of invasive high-grade UC including 14 superficial and 6 muscle-invasive UC cases were used as control. Immunostaining was scored as high for staining of full or more than 50% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity and negative reactivity. All 14 NV/ MV, 3 IP and 6 control cases showed a high score of immunoreactivity for CK5, CD44, CK34bE12 and focally for p63. The remaining control cases showed a high score of immunoreactivity for CK34bE12, while negative or low for CK5, CD44 and p63. In conclusion, immunoreactivity CK5 and CD44 commonly immunostained NV/ MV and some invasive high grade UC. Other basal cell markers ( CK34bE12 and p63) appear to be non specific or non sensitive. NV and MV and some UC likely represent a subset of UC displaying immunohistochemical features of urothelial basal cells. They had tendency of endophytic growth and early invasion despite the innocuous cytologic appearance. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Oncology / Türk Onkoloji Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Perivascular epithelioid cell tumor (PEComa) is a rare but distinct mesenchymal neoplasm composed of histologically and immunohistochemically unique perivascular epithelioid cells. Due to its relative rarity, little is known about the histogenesis and prognostic factors of this tumor. We describe a case of unusual mesenteric PEComa in a 38-year-old female patient with regional lymph node involvement. Histologically, the tumor was composed of sheet of epithelioid cells with abundant clear or eosinophillic cytoplasms. Extensive coagulative necrosis and a few mitotic figures (2/50 high power field) could be found in tumor. The epithelioid tumor cells were diffusely positive for HMB-45, Melan-A, and focally positive for calponin. One of enlarged mesenteric lymph nodes was observed to be involved by tumor. A diagnosis of malignant mesenteric PEComa with lymph node involvement was made. The patient received chemotherapy after total resection of tumor and segmental resection of involved jejunum. There was no sign of recurrence of tumor found in period of 6-month regular follow-up after chemotherapy. To our knowledge, this is the first case of malignant PEComa in mesentery accompanied with regional lymph node involvement. The literature on this rare tumor is reviewed and diagnostic criteria of malignant PEComa are discussed. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/1309992178882788. [ABSTRACT FROM AUTHOR]

Background: Atypical urine cytology results trigger cystoscopy or molecular tests, both of which are costly, complex and difficult to perform tests. Several immunostains are being investigated to improve cancer detection; however, cytology material is limited and restricts the use of multiple immunostains. This study was designed to determine the utility of a cocktail of three stains, cytokeratin (CK20), p53 and CD44 in urine cytology samples for improving the detection of urothelial carcinoma. Materials and Methods: Urine cytology specimens with cell blocks containing adequate cytologic material between 2005 and 2010 and subsequent follow‑up biopsy and/or Urovysion test (102 cases including 29 negative, 56 atypical and 17 malignant) were included in the study and evaluated with the triple stain. Results were first validated on the positive and negative cases and then applied to the atypical cases to determine the utility in the diagnosis of urothelial carcinoma. Results: Based on the validation and published literature, two distinct immunoprofiles were defined – malignant, characterized by at least five CK20 and/or p53 positive atypical cells and reactive, all other staining patterns. The malignant immunoprofile showed 88% sensitivity, 78% specificity, 74% positive predictive value (PPV) and 90% negative predictive value (NPV) for detecting urothelial carcinoma. These values improved to 95% sensitivity and 96% NPV when low‑grade urothelial carcinoma cases were excluded. Summary: Our results indicate that the triple stain is an inexpensive, easy to perform test most useful for differentiating high‑grade urothelial carcinoma from its mimics. Inclusion of CD44 in the cocktail did not provide additional value and is best excluded. [ABSTRACT FROM AUTHOR]

The epithelial-to-mesenchymal transition (EMT) is a crucial program for the invasion and metastasis of epithelial tumors that involves loss of cell-cell adhesion and increased cell mobility; however, mechanisms underlying this transition are not fully elucidated. Here, we propose a novel mechanism through which the nicotinamide adenine dinucleotide-dependent histone deacetylase SIRT1 regulates EMT in prostate cancer cells through cooperation with the EMT inducing transcription factor ZEB1. We found that forced expression of SIRT1 in non-transformed PZ-HPV-7 prostate epithelial cells disrupts the epithelial morphology concomitant with decreased expression of the epithelial marker, E-cadherin, and increased expression of mesenchymal markers. In contrast, silencing SIRT1 in metastatic prostate tumor cells restores cell-cell adhesion and induces a shift toward an epithelial morphology concomitant with increased expression of E-cadherin and decreased expression of mesenchymal markers. We also found that SIRT1 has a physiologically relevant role in endogenous EMT induced by EGF signaling in prostate cancer cells. We propose that the regulation of EMT by SIRT1 involves modulation of, and cooperation with, the EMT inducing transcription factor ZEB1. Specifically, we show that SIRT1 silencing reduces expression of ZEB1 and that SIRT1 is recruited to the E-cadherin proximal promoter by ZEB1 to deacetylate histone H3 and to reduce binding of RNA polymerase II, ultimately suppressing E-cadherin transcription. We thus identify a necessary role for ZEB1 in SIRT1-mediated EMT. Finally, we show that reduction of SIRT1 decreases prostate cancer cell migration in vitro and metastasis in vivo in immunodeficient mice, which is largely independent of any general effects of SIRT1 on prostate cancer growth and survival. We therefore identify SIRT1 as a positive regulator of EMT and metastatic growth of prostate cancer cells and our findings implicate overexpressed SIRT1 as a potential therapeutic target to reverse EMT and to prevent prostate cancer progression. [ABSTRACT FROM AUTHOR]

Capsular contraction is the most common complication of breast reconstruction surgery. While presence of the contractile protein alpha smooth muscle actin (α-SMA) is considered among the causes of capsular contraction, the exact etiology and pathophysiology is not fully understood. The objective of this study was to investigate the possible role of lubricin in capsular formation and contraction by determining the presence and distribution of the lubricating protein lubricin in human breast tissue expander capsules. Related aims were to evaluate select histopathologic features of the capsules, and the percentage of cells expressing α-SMA, which reflects the myofibroblast phenotype. Capsules from tissue expanders were obtained from eight patients. Lubricin, at the tissue-implant interface, in the extracellular matrix, and in cells, and α-SMA-containing cells were evaluated immunohistochemically. The notable finding was that lubricin was identified in all tissue expander capsules: as a discrete layer at the tissue-implant interface, extracellular, and intracellular. There was a greater amount of lubricin in the extracellular matrix in the intimal-subintimal zone when compared with the tissue away from the implant. Varying degrees of synovial metaplasia were seen at the tissue-implant interface. α-SMA-containing cells were also seen in all but one patient. The findings might help us better understand factors involved in capsule formation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012. [ABSTRACT FROM AUTHOR]

A case of intracranial malignant peripheral nerve sheath tumor (MPNST) with uncommon features due to recurrence is reported. The primary tumor showed typical histopathological features of MPNST with wavy nuclei and S-100 positivity. The patient's latest recurrent tumor resembled undifferentiated sarcoma with lipoblast-like multivacuolated cells and hyaline globules (HGs). Ultrastructurally, the vacuolated spaces contained granular materials derived from cystic dilation of the rough endoplasmic reticulum. The HG consisted of round osmophilic inclusions with or without a limiting membrane. The HGs and lipoblast-like multivacuolated cells may have been caused by the degeneration of tumor cells in myxoid stroma and abundant vasculature. [ABSTRACT FROM AUTHOR]

The cell adhesion molecules (CAMs) CD44 standard (CD44s) and its variant 6 (CD44v6) are involved in the progression and invasion of human malignancies. However, discrepancies in the prognostic value of CD44s and CD44v6 expression need to be addressed. Aims: To investigate the expression of CD44s and CD44v6 in bladder carcinomas and relate the results to the established prognostic factors. Materials and Methods: 50 bladder carcinoma specimens, 30 cases with transitional cell carcinoma (TCC: 6 bilharzial and 24 nonbilharzial) and 20 cases with squamous cell carcinoma (SCC: 8 bilharzial and 12 nonbilharzial), were included. Immunohistochemical analysis for CD44s and CD44v6 was carried out using avidin-biotin peroxidase method. Results: The level of both CD44s and CD44v6 in TCC was significantly higher in invasive than in preinvasive tumors and normal urothelium ( p < .05). A direct association between the percentage of expression of both markers and the grade of TCC ( p < .05) was observed. An inverse correlation between CD44s and SCC was seen, where metaplastic urothelium showed higher expression than invasive carcinomas. No association was observed between the expressions of both CD44s and CD44v6 and bilharzial ova, sex and age of the patient, or size of the tumor. Conclusions: The authors report statistically significant correlation between CD44s and CD44v6 expression and increasing grade and stage of TCC. No such correlation with SCC and with bilharzial cystitis, sex and age of the patient, or size of the tumor was documented. [ABSTRACT FROM AUTHOR]

Apoptosis is the distinctive form of programmed cell death that complements cell proliferation in maintaining normal tissue homeostasis. The significance of constitutive apoptosis in the recurrence of Non Muscle Invasive Bladder Cancer has yet to be investigated. The aim of this study is to investigate the prognostic significance of Bax and Bcl-2 in terms of recurrence after BCG immunotherapy. Immunohistochemical analysis was performed on frozen biopsies to evaluate bcl-2 and Bax proteins expression in 28 cases of NMIBC. All patients with confirmed NMIBC were treated with intravesical BCG-immunotherapy. The follow up was performed for 26 months. The correlation between clinicopathological, immunohistochemical data and the response to BCG therapy was performed. Univariate analysis showed that, PT1 stage, High grade and Bax expression increased significantly the risk of recurrence (P == 0.015, P == 0.015 and P== 0.034 respectively). In addition, multivariate analysis selected the model involving stage, age, Bax and Bcl-2 expression as the best independent variables of recurrence. In conclusion, the expression of Bcl-2 and Bax in NMIBC could have a prognostic value in assessing the risk of recurrence after BCG immunotherapy. These findings require further investigations on larger cohort in order to ascertain new molecular markers of the response to BCG immunotherapy. [ABSTRACT FROM AUTHOR]

Copyright of Theologica & Historica is the property of Pontificia Facolta Teologica della Sardegna and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of African Journal of Cancer / Journal Africain du Cancer is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This report with late seromas occurring in the periprosthetic cavity. This complication is a rare development after breast augmentation. From 1996 to 2009, the authors performed 568 initial breast augmentation procedures. During this period, they observed late seromas in six cases. In five of the six cases, the initial operations were performed by the authors (0.88% of all breast augmentation operations performed at the authors' center during the respective period). In one case, the operation had been performed in another clinic. Late seromas occurred at various intervals 2 to 10 years after the initial breast augmentation. In five of the six reported cases, revision surgery was required. In one case, conservative treatment was applied. An implant rupture was observed in only one case. In the remaining five cases, the implants were intact. In the authors' opinion, seromas may occur when any sliding surfaces are present and as a result of micromotion of implants in cavities. The inner surface of a capsule with a synovial metaplasia becomes a target for chronic infections. [ABSTRACT FROM AUTHOR]

The article focuses on a study which tries to determine the role of cell adhesion molecule CD44s in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC). CD44 mediates cellular adhesion to the extracellular matrix, which helps in tumor cell migration. It included 159 patients with resected NSCLC and used immunohistochemical staining to investigate CD44s protein expression. The result show that high CD44s expression was a negative prognostic marker for NSCLC patients.

Periprosthetic capsules are a common reaction of the body to silicone or polyurethane breast implants. The aim of this study was to evaluate similarities and differences in the histological features of periprosthetic capsules surrounding silicone implants and polyurethane foam-coated implants and to correlate those features with the age of the implants. Tissues were studied from 41 periprosthetic capsules surrounding textured prostheses and from 20 capsules surrounding polyurethane foam-coated implants. For each sample we evaluated synovial metaplasia, density of collagen fibers or fibrosis, orientation of collagen fibers, and foreign body reaction (granulomatous reaction). Synovial metaplasia was seen in the capsular tissue from both types of implant, but more so from capsules surrounding polyurethane implants more than 5 years old. The density and orientation of the collagen fibers and the foreign body reaction were very similar for the two types of implant. [ABSTRACT FROM AUTHOR]

Chordoma are slow growing, locally destructive tumors derived from remnants of notochord. They occur mostly along axial skeleton that is basiocciput and sacrococcygeal area. are biphasic malignant neoplasm possessing elements of both chordoma and cartilaginous tissue, an entity which has better prognosis than classical Chordoma. The tumor is likely to recur and hence diagnostically important for appropriate management. Histopathologically, tumor showed chords or nests of cells with partly vacuolated cytoplasm (physaliferous cells) embedded in a myxoid matrix and extensive cartilage formation with degenerative calcification was seen. Immunohistochemically, tumor was positive for Cytokeratin and EMA and negative for S-100 except for Cartilaginous areas which were S-100 positive. We report a case of Chondroid chordoma in a 50 year male presented with intermittent radiating pain in both leg and backache for 1 year. MRI lumbosacral showing the tumor in posterior elements if L5 S2 vertebra. Chondroid chordoma is a distinct entity to be discriminated from typical type of Chordoma because of its better prognosis. MRI cannot differentiate between Chondroid chordoma and typical chordoma. Awareness of this rare tumor will avoid misdiagnosis and improve the prognosis. A wide surgical excision coupled with adjuvant radiation is the best treatment in the present case. [ABSTRACT FROM AUTHOR]

Systematic reviews indicate that breast implant texture confers a protective effect on capsular contracture. Fibroblasts are affected by micro- and nanotopographies. Few previous studies have investigated the inherent topographies of existing breast implants and the surfaces with which body tissue is exposed. Aims: To examine currently available breast implant surfaces at high resolution and evaluate features within their surface that have been demonstrated to influence fibroblast alignment. Methods: Using scanning electron and light microscopy, 5 distinct smooth and textured silicone implants including the Mentor Siltex® (Mentor Corporation, Santa Barbara, Calif) and Allergan Biocell® (Allergan Medical Corporation, Santa Barbara, Calif) surfaces were investigated at high magnification to illustrate their intrinsic surface topographies. Results: The images obtained illustrate remarkable micro- and nanoscale topographies. Each surface produced a distinctive microenvironment capable of influencing cell shape and thus biointegration. These features are illustrated by our unique, high-magnification images. The smooth surface exhibits a shallow, regular, 5-μm period rippled texture that may explain higher reported contracture rates, while the Biocell and Siltex surfaces show 100- to 200-μm deep but random features that have been shown to anchor the implant to breast tissue and reduce contracture. Results allow a cell's eye view of these implants, with an explanation of why these types of topographies influence the success of these implants. Conclusions: We assessed commonly available silicone implants and offer a unique overview into their surface topographies and how they are manufactured. We conclude that these surfaces require modernization. Our findings provide further insight into potential interactions between cellular assemblies and artificial surfaces and may contribute to the development of improved implant surfaces. [ABSTRACT FROM AUTHOR]

The article presents a study on uropathology focusing on prostrate cancer. Prostate cancer is cited as the most prevailing cancer among men and represents 9.7% of irremediable carcinoma. The goal of the research is to evaluate the importance of current tumor biomarkers compared with the conventional characteristics depicted in its development, advancement and subsistence. The methodology used utilized molecular strategies conducted among prostate cancer patients through radical prostatectomy.

Abstract  The perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. PEC expresses myogenic and melanocytic markers, such as HMB45 and actin. Recently, recurrent chromosomal alterations have been demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past 10 years, the use of this term has allowed to report and describe numerous cases permitting to start highlighting the biology of this group of lesions. PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway. There are some open questions about PEComas regarding its histogenesis, the definition of epithelioid angiomyolipoma and the identification of the histological criteria of malignancy. An innovative therapeutic trial using rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma and lymphangioleiomyomatosis. Its success could provide the rationale for the use of the same drug in other lesions composed of PECs, especially in the malignant ones. [ABSTRACT FROM AUTHOR]

Abstract  Possible prognostic utility of CD44 in renal cell carcinoma (RCC) prompted a comparison of its expression in primary and metastatic RCC. A total of 164 paraffin-embedded tissues of primary RCC and metastatic RCCs from 125 patients were immunostained with CD44 (standard form) antibody. It consisted of 86 primary RCCs (50 with subsequent metastasis [MET] and 36 with no known metastasis [MET−]) during follow up and 78 metastatic RCCs (39 metastatic RCCs only and 39 with matched RCC primary from RCC MET category). Immunoreactivity for CD44 was scored semiquantitatively as 0, 1, or 2 (0, p = 0.036). CD44 immunoreactivity in the primary RCC (MET− and MET) correlated with progression-free survival (p = 0.027). In metastatic RCCs, CD44 immunoreactivity also correlated with survival after detection of first metastasis (p = 0.011). In multivariate analysis, stage (p = 0.0001) and CD44 immunoreactivity (p = 0.03) in primary RCC were independent predictors of progression-free survival. Our study suggests that CD44 status in RCC provides useful prognostic information both in primary and metastatic RCCs and may have applicability in stratifying patients for therapeutic decisions. [ABSTRACT FROM AUTHOR]

We tested the suitability of the chimeric monoclonal anti-human CD44 splice version 6 antibody (cMAb U36) for targeting and visualising human anaplastic thyroid carcinoma with PET. We also performed experiments aimed at elucidating the relation between tumour interstitial fluid pressure (TIFP) and the tumour uptake of antibodies. The affinity and specificity of the cMAb U36 for KAT-4 cells were evaluated in vitro, as was the Na+/I− symporter (NIS) expression. Biodistribution studies were performed on KAT-4 carcinoma-bearing mice injected with 124I-cMAb U36 or free iodine. Biodistribution studies were also performed in animals treated with the specific TGF-β1 and -β3 inhibitor Fc:TβRII, which lowers TIFP. Treated and non-treated animals were scanned by microPET. Cultured human undifferentiated/anaplastic thyroid carcinoma KAT-4 cells expressed low levels of NIS and uptake of free iodine was insignificant. The cMAb U36 expressed an affinity ( K D) of 11 ± 2 n M. Tumour radioactivity uptake reached maximum values 48 h after injection of 124I-cMAb U36 (∼22%IA/g). KAT-4 carcinomas were readily identified in all 124I-immuno-PET images. Radioactivity tumour uptake in Fc:TβRII-treated animals was significantly lower at 24 and 48 h after injection, and five times higher thyroid uptake was also noted. We successfully used 124I-cMAb U36 to visualise CD44v6-expressing human anaplastic thyroid carcinoma. Given the lack of NIS expression in KAT-4, tumour visualisation is not due to free iodine uptake. Lowering the TIFP in KAT-4 carcinomas did not increase the uptake of mAbs into tumour tissue. [ABSTRACT FROM AUTHOR]

To report a case of a 31-year-old woman with renal angiomyolipoma (RAML) who presented with progressive massive haematuria with successive pregnancies. A 28-year-old woman presented with mild haematuria in the third trimester of her second pregnancy. This was due to bleeding from a left RAML. Patient became pregnant for a third time. The RAML increased in size and patient bled more during the third trimester. After delivery she refused partial nephrectomy or renal␣embolisation. In the third trimester of the fourth pregnancy, she presented with massive haematuria, shock, severe anaemia (haemoglobin of 6gm/l) and required a total of 26 units of blood transfusion during a 4-week period. She required emergency Caesarian section at 36 weeks and simple nephrectomy 3 months postpartum. The risk of profuse haemorrhage from RAML may increase with successive pregnancies in women with RAML. This anomaly should be treated in between pregnancies by either angioembolisation or resectional surgery. [ABSTRACT FROM AUTHOR]

Objective: To assess if the percentage of cancer in prostate needle biopsies provides independent prognostic information for predicting pathological stage and/or biochemical relapse after radical prostatectomy. Methods: One hundred and forty prostate cancer patients who underwent radical prostatectomy were evaluated. Preoperative parameters analyzed were patient age, PSA, clinical stage, and the information obtained from sextant biopsies (Gleason score, maximum percentage of cancer in a core, percentage of tissue with cancer in all biopsies and the number of cores positive for cancer). Univariate and multivariate analyses (logistic regression) for the dependent variables (prostate cancer, organ-confined and biochemical relapse) were performed. Results: The tumor was organ-confined in 73.6% of patients. In those patients studied for disease progression (n = 126), no biochemical recurrence was observed in 76.2%. In the multivariate analysis for organ-confined disease, the total percentage of biopsy tissue with cancer, the preoperative PSA level, the Gleason score and the clinical stage were the most accurate predictive factors of pathological stage. The multivariate analysis for the study of biochemical failure indicated that only the total percentage of biopsy tissue with cancer, the preoperative PSA level and the Gleason score were independent predictive factors. According to the logistic regression analysis for disease recurrence, 3 risk groups could be identified: low risk (less than 10% probability of disease progression), intermediate risk (30%) and high risk (more than 70%). Conclusions: The percentage of cancer in prostate biopsy provides independent prognostic information for predicting pathological stage and the risk of biochemical failure after radical prostatectomy. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims : To clarify the relationship between ubiquitin-positive pneumocytes and intracytoplasmic eosinophilic inclusion bodies (IB) in patients who died of diffuse alveolar damage (DAD). Methods and results : Eighteen patients with DAD were studied, in whom hyaline membranes were present in one or more out of five sections from each lobe of the lungs and 15 patients with no DAD. Light microscopy revealed hyaline membrane in over 25% of lobes from 18 patients with DAD. The cytoplasm of pneumocytes from six of 18 cases of DAD contained IB. Immunohistochemically, all IBs were characteristically positive for both ubiquitin (Ub) and cytokeratin KL-1. Cytoplasmic granules were also Ub+ in four cases of DAD without IB. IB+ or Ub+ pneumocytes were undetectable in non-DAD patients. We evaluated DAD severity based on hyaline membrane formation; the mean score in DAD with IB (3.60; n = 6) was significantly higher than that in Ub– (2.92; n = 8). Ub+ pneumocytes were found with or without IB among those cases with high DAD scores. Conclusions : These findings suggest that disordered proteolysis in the Ub-mediated proteasome system leads to the accumulation of abnormal ubiquitinated protein, which includes cytokeratin, in pneumocytes. This is the first report to suggest that Ub+ pneumocytes are associated with disease severity in patients with DAD. [ABSTRACT FROM AUTHOR]

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking. [ABSTRACT FROM AUTHOR]

Objective: The clinical course of transitional cell carcinoma is highly variable. The determination of sensitive prognostic factors for transitional cell carcinoma is very important. Therefore e-cadherin and p53 immunohistochemical activity can be used with other prognostic factors. Methods: The study comprised with 61 (4 women and 57 men) selected patients who had transitional cell carcinoma. Paraffin embedded tissue sections were investigated immunohistochemically for e-cadherin normal staining and p53 over expression. Results: It is seen that when grade and stages of illness increased normal staining of e-cadherin decreased and p53 over expressed. Abnormal e-cadherin was significantly associated with disease recurrence ( P < 0.001), disease progression ( P < 0.001) and bladder specific survival. p53 differentiation was not significant for disease recurrence ( P > 0.05) inverse to prognosis of illness. Transurethral resectomy and BCG treatments were not effected e-cadherin and p53 activity within the groups statistically. Conclusion: Significant differences can be helpful to investigate patients more detailed pathologically. These expression rates in different type of transitional cell carcinoma patients may represent a biologically more aggressive cancer, requiring early definitive therapy. This hypothesis should be evaluated in larger studies and prospective clinical trials. [ABSTRACT FROM AUTHOR]