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CD44 cell adhesion molecule (PgP-1, ECM III, Hermes antigen) is a polymorphic integral membrane glycoprotein associated with cell matrix adhesion, lymphocyte activation, recirculation, and homing. CD44 expression has been reported in in malignant lymphoma and in a variety of epithelial human cancers but has not been studied as a prognostic marker in urinary bladder transitional cell carcinoma. CD44s (standard 85- to 95-kDa macromolecule) expression was measured by qualitative and image analysis-quantitated immunohistochemical techniques using the A3D8 monoclonal antibody. CD44v6 (a splice variant exon of CD44s) expression was measured by qualitative immunohistochemical techniques using the 2F10 monoclonal antibody. The results of CD44s and CD44v6 expression were compared with tumor grade, pathologic stage, and DNA content analysis on Feulgen-stained tissue sections in 44 cases of urinary bladder transitional cell carcinoma. The mean percentage-positive area of staining intensity for CD44s expression in Grade 1 tumors was 61%, compared with 30% for the Grade 3 tumors (P < 0.001). Non-invasive tumors featured a 59%-positive area of staining intensity, compared with the 30% staining percentage for the deeply invasive tumors (P < 0.001). There was significant correlation of aneuploid DNA content with loss of CD44s staining (P < 0.05). The staining results for CD44v6 paralleled those for the CD44s, with a significant loss of staining in high-grade and high-stage aggressive tumors in comparison with the low-grade nonaggressive tumors (P < 0.01). In urinary bladder transitional cell carcinoma, CD44s and CD44v6 expression parallels that for other cell adhesion molecules, such as E-cadherin, that feature a significant progressive loss of immunoreactivity in association with tumor dedifferentiation, advancing pathologic stage, and abnormal DNA content.

Recent descriptions of numerous pitfalls in the cytologic diagnosis of thyroid papillary carcinoma on fine-needle aspiration biopsy specimens have prompted studies of new ancillary diagnostic methods. We evaluated the potential use of immunocytochemical staining of thyroid fine-needle aspiration biopsy specimens for CD44, a glycosylated cartilage link protein associated with extracellular matrix adhesion and lymphocyte homing. Fourteen of 16 (88%) classic, surgically confirmed, thyroid aspiration biopsies stained intensely positive for this marker, whereas 0 of 30 (0%) similarly-processed benign aspirates from colloid nodules showed immunoreactivity for CD44 antigen. From this study, we conclude that most papillary carcinomas of the thyroid express the celladhesion molecule CD44, which may be of clinical value in confirming the diagnosis on borderline fine-needle aspiration specimens. Further study of CD44 expression may prove of significant interest in explaining the unusual mode of spread and clinical course of this disease.

E-cadherin (E-CD) is a cell-adhesion molecule that has been associated with invasion and metastasis in a wide variety of human neoplasms. We have recently shown that, although decreased E-CD expression is associated with increased bladder-wall invasion and higher tumor grade of infiltrating transitional cell carcinomas (TCC), E-CD expression in the exophytic portion of pure papillary and papillary-infiltrating TCC is increased over that of normal transitional cells. To evaluate whether E-CD levels could serve as a diagnostic adjunct in urinary cytology specimens, we stained 40 alcohol-fixed bladder-washing cytospin preparations with an avidin-biotin-peroxidase method using a monoclonal antibody to E-CD (Sigma Chemical Co., St. Louis, MO). E-CD expression level was defined as a high-intensity or low-intensity staining increase over background squamous cell staining for the transitional cells in 21 biopsy-proven transitional cell carcinomas with papillary components, and in 19 benign or reactive control specimens. Twenty-one of 21 TCC (100%) showed an increased E-CD level over background, with 13 low-intensity and 8 highintensity cases. Ten of 19 benign cases (53%) showed increased E-CD staining over background, with 8 low-intensity and 2 highintensity cases. This difference between malignant and benign specimens was statistically significant (chi-square test. P approximately 0.001). We conclude that increased E-CD expression in the papillary components of TCC can be identified in urinary cytology specimens, may reflect the physical and chemical structural makeup of papillary architecture, and warrants further study as a diagnostic adjunct in the interpretation of urine cytology specimens.

E-cadherin (E-CD), a cell adhesion molecule that plays a diverse role in cell-cell and cell-matrix interaction, has recently been associated with tumor invasion and metastasis. We evaluated the E-CD expression in 55 cases of urinary bladder papillary transitional cell carcinoma using a double-linked immunoalkaline phosphatase procedure on formalin-fixed, paraffin-embedded specimens quantified as percentage positive staining area with the Roche RPW image analyzer (Roche Image Analysis Systems, Elon College, NC). The 10 grade I tumors stained intensely for E-CD (66%) and showed enhanced staining compared with normal transitional epithelium. The 20 grade II lesions stained moderately at 45%, and the 25 grade III lesions showed weak expression of E-CD with a 33% positive stain. This loss of expression for high-grade versus low-grade tumors was statistically significant (P < .02). There was a similar decrease in E-CD expression for high-stage versus low-stage specimens with 30 stage 0 and stage A cases having an average of 51% positive stain and 25 stage B, C, and D cases having an average stain of 33%. This difference was also statistically significant (P < .001). We conclude that loss of expression of E-CD in high-grade, high-stage urinary bladder transitional cell carcinoma is associated with significant bladder wall invasion, indicates potential for metastasis, and may be of clinical value in the assessment of prognosis and planning of therapy for patients with bladder tumors.

The formation of true synovial-lined membranes at tissue sites not intimately related to an articulation or a tendon sheath has been described in a variety of pathologic and postsurgical conditions, but until recently has not been well recognized to occur in association with tissue surrounding silicone breast implants. Of 15 cases with resected periprosthetic breast capsules, 7 (47%) demonstrated true synovial metaplasia with capsule-implant interfaces lined by typical synovial cells. Histochemical and immunohistochemical staining reactions were essentially identical to those observed in synovial control cases and featured positive reactions to Alcian blue-periodic acid-Schiff, reticulin, and vimentin. Focal positive immunoreactivity was observed with alpha 1-antitrypsin, alpha 1-antichromotrypsin, lysozyme, and CD68. No immunoreactivity was observed with cytokeratin AE1/AE3, S-100 protein, carcinoembryonic antigen, or basement membrane antigens. Transmission electron microscopy of the lining cells confirmed their true synovial nature with the type A (macrophage-like) cells, type B (fibroblast-like) cells, and intermediate forms or type AB cells identified. We conclude that the cellular lining surrounding silicone breast implants is a true synovial membrane, that synovial metaplasia may occur in nearly one half of all resected periprosthetic capsules, and that awareness of this entity will enable the surgical pathologist to render an accurate histopathologic diagnosis.

Hyaline globules (HGs), spherical intracytoplasmic eosinophilic droplets, have been associated with a variety of conditions, including hepatocellular carcinoma, lung adenocarcinoma, and Kaposi's sarcoma, but they have not been described in cartilaginous tumors. In specimens of 60 cartilaginous neoplasms we found that 22 of 33 chondrosarcomas (67%), eight of 16 enchondromas (50%), and three of seven soft tissue chondromas (43%) exhibited HGs. HGs were seen more commonly in low grade chondrosarcoma (70%) and were relatively rare in high grade chondrosarcoma (25%). No HGs were identified in three osteochondromas, one synovial chondromatosis, or 15 normal cartilaginous tissues taken from various sites. Cartilage associated HGs ranged in size from 2 to 20 microns, were diastase resistant and periodic acid-Schiff (PAS) stain positive, demonstrated autofluorescence, and variably stained with Mallory's phosphotungstic acid-hematoxylin stain (PTAH). A panel of immunostains did not show any specific staining reactions with HGs. Ultrastructurally the HGs were spherical, non-membrane-bound bodies having complex architectural features associated with profiles of rough endoplasmic reticulum. Electron probe x-ray microanalytic (EPXMA) study showed significant peaks of sulphur and calcium. We conclude that HGs represent secretory products of probable glycoprotein nature, may accumulate in a variety of cartilaginous neoplasms, and may be seen more frequently in low grade chondrosarcomas.

CD44 is a polymorphic family of immunologically related integral membrane glycoproteins associated with cell matrix adhesion, lymphocyte activation and targeting, and tumor growth and metastasis. We studied CD44 expression in 114 formalin-fixed paraffin-embedded thyroid tumors using the A3D8 anti-human CD44 monoclonal antibody. Sixty-five of 67 papillary carcinomas (97%) strongly expressed CD44 with an intense plasma membrane pattern. Thirty-seven of these cases originated from Albany, New York, and 30 cases from Russia. Immunoreactivity was also observed in 9 of 16 follicular adenomas (56%); 4 of 8 Hurthle cell neoplasms (50%); 5 of 15 medullary carcinomas (33%); and 3 of 8 follicular carcinomas (38%). These results show that among thyroid neoplasms, papillary carcinomas preferentially display the CD44 antigen (P < or = 0.001). Nonneoplastic follicular epithelium exhibited a low to moderate level of staining. To further characterize the CD44 isoform, we tested a subset of cases with the 2F10 anti-human CD44 variant 6 monoclonal antibody, which recognizes a CD44 variant exon (CD44v6) implicated in tumor metastasis. Eleven of 11 papillary carcinomas tested were 2F10 positive, and 1 of the follicular carcinomas was positive. These results suggest the hypothesis that deregulated CD44v6 expression on the plasma membrane of papillary carcinoma cells contributes to the ability of those cells to metastasize to regional lymph nodes and then to remain dormant for years. Our results suggest that human papillary thyroid cancer will be an interesting model in which to further study the role of CD44 isoforms, particularly those containing CD44v6, in tumor metastasis and lymphatic invasion.

Background: DNA ploidy determination of carcinomas in radical prostatectomy specimens has shown significant correlation with patient outcome, but the predictive value of ploidy status of cancers obtained by transrectal ultrasound-guided needle biopsies has not been studied extensively., Methods: Eighty-nine paired needle biopsy specimens (NBX) and radical prostatectomy (RPX) specimens from patients with early clinical stage (A2-B2) prostate cancer were evaluated for DNA content by image analysis of Feulgen stained tissue sections. Findings were compared with Gleason grading on the same specimens by univariate and multivariate analyses for prediction of local tumor invasion, metastasis, disease recurrence, and serum prostate specific antigen concentration during a 0.9-6.0 year clinical follow-up period., Results: There was excellent correlation of ploidy status between NBX and RPX specimens (P < 0.0001); NBX and RPX grades did not correlate. On RPX specimens, aneuploid status correlated with high tumor grade (P < 0.0005). Aneuploidy in NBX specimens was associated with a twofold higher rate of extracapsular spread (ECS) (P = 0.04). Aneuploid NBX tumors featured a tenfold greater frequency of metastasis than did diploid NBX tumors (P < 0.005). Radical prostatectomy grade correlated with ECS (P < 0.001) and presence of metastatic disease (P = 0.04). On multivariate logistic regression analysis, aneuploidy in both NBX and RPX specimens was the most significant variable and independently predicted the presence of metastasis (P = 0.006 for NBX; P = 0.028 for RPX). Tumor grade of NBX and RPX specimens did not independently predict metastatic disease or disease recurrence, but RPX grade was associated independently with ECS (P = 0.005). Aneuploid NBX tumors recurred after RPX three times more often than did diploid cases, which was significant on univariate (P < 0.001) and multivariate (P = 0.018) analyses using the Cox proportional hazards model. There was no correlation with NBX or RPX Gleason score and disease recurrence. Preoperative serum PSA concentration did not correlate with tumor grade or ploidy status, but on multivariate analysis, when paired with ploidy status, independently contributed to the propensity for ECS, metastasis, and disease recurrence., Conclusions: DNA content analysis of early clinical stage prostate carcinoma needle biopsy specimens by image analysis directly correlates with radical prostatectomy specimen ploidy status and is associated independently, with the presence of metastasis, postprostatectomy disease recurrence, and ECS. Needle biopsy tumor grading did not correlate with prostatectomy grade and did not predict disease outcome accurately.

We compared tumor grade and DNA content with expression of E-cadherin (E-CD), a cell adhesion molecule associated with cell-cell and cell-matrix interaction, leukocyte function, and tumor invasion and metastases, on 56 prostate carcinoma needle biopsies. The findings were correlated with final pathologic stage at subsequent prostatectomy, preoperative serum prostate-specific antigen level and further development of metastases during an initial 2.4-yr mean clinical follow-up period (range 0.5 to 5.5 yr). E-CD expression (uvomorulin, L-CAM, cell CAM 80/120, ARC-1, Sigma, St. Louis, MO) was measured by double-linked immunoalkaline phosphatase immunohistochemistry quantified with a the Roche RPW image analyzer (Roche Image Analysis Systems, Elon College, NC). DNA ploidy was determined on formalin-fixed, paraffin-embedded Feulgen-stained 5-microns tissue sections of the narrow-bore initial prostate carcinoma biopsies with the Roche RPW image analyzer. The 51% mean positive area E-CD expression in the group of 56 adenocarcinomas was significantly less than the 76% expression level for 15 normal control prostate tissues (P < 0.001). E-CD expression was also decreased in aneuploid (39%) versus diploid tumors (54%, P < 0.001); and in high-grade (44%) versus low-grade lesions (54%; P < 0.01). The 44% E-CD expression level in patients with metastases was lower than the 52% level in the nonmetastatic cases, but this finding was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiomyolipomas (AMLs) are polymorphic renal tumors that are composed of mature tissues and frequently associated with tuberous sclerosis; AMLs have long been considered hamartomatous in nature. We report the routine histologic and immunohistochemical features and DNA content analysis of two fatal cases of renal giant multicentric AML with distant organ involvement, and we contrast the findings with those of four similarly studied cases of classic solitary AML. Severe nuclear pleomorphism, significant mitotic activity, and necrosis, which are all characteristics of multicentric AML, were not seen in the cases of classic AML. Quantitation of DNA by image analysis of Feulgen-stained slides from paraffin-embedded blocks revealed an aneuploid pattern in the two cases of multicentric AML and an aneuploid pattern in one of the four cases of classic AML. Tumors in the liver, spleen, and lungs in one of the cases of multicentric AML were diploid. Immunohistochemical analysis revealed positive staining reaction of vascular and adipose tissue components with HMB-45 antibody in three of the six cases of AML. We conclude that AMLs may occur in a sarcomatous, infiltrating multicentric form involving multiple organs, that aneuploidy may be seen in lesions of both the multicentric AML and classic AML variants, that AMLs may feature DNA ploidy heterogeneity in multiple-organ sites, that HMB-45 immunoreactivity may be encountered in AMLs without evidence of nevomelanocytic differentiation, and that continued study of AMLs is needed to clarify further the histogenesis, lineage, clonality, and malignant potential of these tumors.

Prostatic intraluminal crystalloids are irregular eosinophilic, non-birefringent structures increasingly recognized as potential indicators of prostatic malignancy. In a study of 250 randomly selected surgical pathology cases of prostatic tissues none of 50 cases of benign glandular hyperplasia (0%), one of 50 cases of atypical adenomatous hyperplasia, 18 of 50 cases of well-differentiated adenocarcinoma (36%), seven of 50 cases of moderately differentiated adenocarcinoma (14%), and none of 50 cases of poorly differentiated adenocarcinoma (0%) revealed intraluminal crystalloids. A histochemical and immunohistochemical staining panel indicated that the crystalloids were nonproteinaceous. Crystalloids were stained intensely with phosphotungstic acid hematoxylin and did not stain for prostatic-specific antigen or hemoglobin. Crystalloids were clearly differentiated from prostatic corpora amylacea on light microscopy, histochemistry, scanning, and transmission electron microscopy. Electron probe x-ray microanalysis of 10 cases of crystalloids revealed uniform high sulfur peaks and small sodium peaks. We conclude that intraluminal crystalloids are associated more frequently with low-grade prostatic adenocarcinoma, may occur in benign tissue bordering adenocarcinoma, are predominantly composed of inorganic sulfur, and their presence in benign and atypical prostate biopsies may be of pathologic significance and should warrant further clinical investigation and possibly repeat biopsy.

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., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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]

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]

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]

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]

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]