Primary eosinophilic gastroenteritis and colitis (EGE) is a rare entity with unspecific clinical and endoscopic findings. Validated histopathologic criteria for confirming the diagnosis are lacking, because numeric values for normal or elevated concentrations of eosinophils in mucosal biopsies are varying between observers. To quantify this interobserver variance, we had the same set of 30 slides of eosinophilic-rich mucosal biopsies from the ileum and colon systematically reviewed by a panel of six independent pathologists, each with more than a ten-year experience in the field. Using a highly standardized biopsy and slide preparation protocol, we ruled out any influence by the preparation, the patient, the endoscopist, the endoscopes and calipers used, the sampling site, the fixation and staining method, and the microscopic field sizes. Still, all numeric results differed between pathologists up to a factor greater than 30. Calculated positive or negative diagnosis of EGE differed up to a factor greater than 8. A theoretical incidence for EGE calculated from these numbers differed by a factor greater than 1500. We conclude that eosinophil counts in mucosal biopsies from the lower gastrointestinal tract are subject to a very high interobserver variance. Until further research provides objective and validated methods for standardization, all epidemiologic numbers derived from histopathologic findings may have to be questioned. When diagnosing individual patients with EGE, overall morphologic picture together with clinical and endoscopic findings is more important than numeric eosinophil count.

Florian Hentschel

Anna Franziska Jansen

Marlis G&#xfc;nther

Roland Pauli

Stefan L&#xfc;th

Eosinophil Counts in Mucosal Biopsies of the Ileum and Colon: Interobserver Variance Affects Diagnostic Accuracy

<i>Background and Objective</i>. Evidence for the roles of matrix metalloproteinases-9 (MMP-9) in the healing process of diabetic foot ulcers has remained unclear. We therefore aimed to demonstrate the relationship of MMP-9 with the wound healing process and determine its potential usefulness in predicting the wound healing outcome.<i> Methods</i>. Twenty-two patients with diabetic foot ulcer were recruited. The wound size was determined, and the wound fluid was collected for the measurement of MMP-9 levels using an ELISA during the 12-week follow-up period regularly. The patients were categorized as good healers and poor healers when the wound area reduction was &#x2265; 50&#x25; and &#x3c; 50&#x25; at week 4 when compared to the initial wound size at week 0.<i> Results</i>. Median wound fluid MMP-9 levels in the poor healer group were shown to be significantly higher than those in the good healer group (1.03 pg/<i>&#xb5;</i>g protein vs. 0.06 pg/<i>&#xb5;</i>g protein, p = 0.001), and the levels fluctuated throughout the 12-week follow-up period. In contrast to the poor healer group, the MMP-9 levels were demonstrated to be constantly low throughout the follow-up period in the good healer group. ROC analysis showed that the MMP-9 level of 0.38 pg/<i>&#xb5;</i>g protein was able to predict the wound healing outcome with the sensitivity of 81.8&#x25;, the specificity of 64.6&#x25;, and the area under the curve of 0.901 (CI 0.78-1.03, p = 0.001).<i> Conclusion</i>. These findings suggested that determination of wound fluid MMP-9 levels might become a promising biomarker predicting wound healing outcomes and a novel potential therapeutic target for diabetic foot ulcers.

Punyanuch Jindatanmanusan

Sivat Luanraksa

Tanit Boonsiri

Thirayost Nimmanon

Pasra Arnutti

Wound Fluid Matrix Metalloproteinase-9 as a Potential Predictive Marker for the Poor Healing Outcome in Diabetic Foot Ulcers

<i>Aim.</i> Antigenic expression in epithelial cells can be heterogeneous which may pose a problem in immunohistochemical (IHC) analysis of tumor markers, in particular, predictive markers like HER2. Studies have shown that epithelial cells have distinct apical and basolateral domains which are separated by tight junctions. The cell membrane in these two domains has a different composition of macromolecules and hence can have variable antigen expression on immunohistochemistry. In our study, we aimed to investigate this phenomenon of basolateral versus circumferential IHC staining of HER2 in gastric/GE adenocarcinoma.<i> Methods.</i> We selected 45 cases of gastric/GE adenocarcinoma and evaluated equal number of specimens (15 each) showing well-differentiated, moderately differentiated, and poorly differentiated morphology. All cases had 3+ HER2 score as per CAP guidelines. HER2-membrane staining pattern in all specimens was analyzed.<i> Results.</i> Cases with well-differentiated morphology showed only basolateral or lateral membrane staining in most cases. Poorly differentiated adenocarcinoma samples showed circumferential staining (both basolateral and luminal) in all cases with highly significant p value. Mixed staining pattern was observed in moderately differentiated cases. Diffuse expression of E-cadherin in well-differentiated adenocarcinoma and loss in poorly differentiated tumors were also statistically significant.<i> Conclusion.</i> These findings suggest that HER2 in gastric epithelium has a polarized distribution which is maintained by the fence function of tight junctions. With progression to high grade cancer, the glandular structural differentiation in gastric mucosa is lost, along with disruption of tight junctions. This leads to loss of cell polarity and migration of antigens across the membrane.

Shahid Pervez

Sidra Arshad

Brooj Abro

HER2 Basolateral versus Circumferential IHC Expression Is Dependent on Polarity and Differentiation of Epithelial Cells in Gastric/GE Adenocarcinoma

<i>Background</i>. Classification of patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) into histological classes is useful for predicting a patient&#x2019;s risk of progression to end-stage renal disease (ESRD). However, even in the worst prognostic group, the 5-year end-stage renal disease-free survival rate is as high as 50&#x25;.<i> Objectives</i>. To investigate those prognostic factors indicative of progression to ESRD in patients with ANCA-GN and sclerosing histology.<i> Methods</i>. Patients from the Norwegian Kidney Biopsy Registry between 1991 and 2012 who had biopsy verified pauci-immune glomerulonephritis, positive ANCA serology, and sclerosing histology were included. Cases with ESRD during follow-up were identified via linkage with the Norwegian Renal Registry. Potential prognostic factors with relevant cut-offs were compared in patients with and without progression to ESRD during follow-up.<i> Results</i>. Of 23 included patients, 10 progressed to ESRD. ESRD patients had a lower initial estimated glomerular filtration rate (eGFR; 21 versus 52&#x2009;ml/min/1.73&#x2009;m<sup>2</sup>) and a lower percentage of normal glomeruli (4&#x25; versus 15&#x25;). Five-year risks of ESRD with eGFR &#x3e;15 versus &#x2264;15&#x2009;ml/min/1.73&#x2009;m<sup>2</sup> were 77&#x25; and 15&#x25;, with percentage normal glomeruli &#x3e;10&#x25; versus &#x2264;10&#x25;, 83&#x25; and 39&#x25;.<i> Conclusions</i>. eGFR and percentage of normal glomeruli are strong risk factors for ESRD in ANCA-GN with sclerosing histology.

Rune Bj&#xf8;rneklett

Vilde Solbakken

Leif Bostad

Anne-Siri Fismen

Prognostic Factors in Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis with Severe Glomerular Sclerosis: A National Registry-Based Cohort Study

<i>Background</i>. The diagnosis of Osteosarcoma (OSA) is not always straightforward. OSA may resemble Other Primary Bone Tumours (OPBT). The diagnosis of osteosarcoma is sometimes difficult especially in a very small specimen. Immunohistochemistry is one of ancillary testing types that can help the diagnosis of many tumours. The aim of this study was to evaluate the validity of Osteocalcin (OCN) and Alkaline Phosphatase (ALP) immunohistochemistry in discriminating OSA from OPBT.<i> Method</i>. This study included 50 selected human primary bone tumours, 25 cases of OSA and 25 cases of OPBT. Immunohistochemical evaluation of OCN and ALP was done for all cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated.<i> Result</i>. The mean age of OSA and OPBT patients was <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.222pt" style="vertical-align:-0.3499298pt" id="M1" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 32.222 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g><g transform="matrix(.013,0,0,-0.013,12.481,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,15.445,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.013,0,0,-0.013,24.591,0)"><path id="g117-37" d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.974pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="35.0771838 -8.34882 21.974 8.69875"><g transform="matrix(.013,0,0,-0.013,35.127,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,41.367,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,47.608,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,50.572,0)"><use xlink:href="#g113-55"/></g></svg></span> and <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.221pt" style="vertical-align:-0.3499298pt" id="M2" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 32.221 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,24.59,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.975pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="35.076183799999995 -8.34882 21.975 8.69875"><g transform="matrix(.013,0,0,-0.013,35.126,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,41.366,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.013,0,0,-0.013,47.606,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,50.57,0)"><use xlink:href="#g113-52"/></g></svg></span> years, respectively. Osteocalcin was positive in 17/25 (68%) cases of OSA and 16/25 (64%) cases of OPBT (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M3" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg></span>). Alkaline Phosphatase was positive in 24/25 (96%) cases of OSA and 5/25 (20%) cases of OPBT (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg></span>). The sensitivity of OCN in OSA diagnosis was 68%, with specificity, PPV, NPV, and overall accuracy being 36%, 52%, 53%, and 52%, respectively. The sensitivity of ALP in OSA diagnosis was 96%, with specificity, PPV, NPV, and overall accuracy being 80%, 82.7%, 95.2%, and 88%, respectively.<i> Conclusion</i>. ALP immunohistochemistry is useful in discriminating OSA from OPBT. ALP is superior to OCN in OSA diagnosis. OCN cannot be used to differentiate between OSA and OPBT.

Hasrayati Agustina

Ita Asyifa

Afiati Aziz

Bethy S. Hernowo

The Role of Osteocalcin and Alkaline Phosphatase Immunohistochemistry in Osteosarcoma Diagnosis

<i>Objective</i>. B lymphocyte infiltration in the tumor microenvironment has been proposed to play pivotal roles in tumor progression. Heat shock protein 70 (HSP70) expressed by tumor cells can induce antitumor immune response. Few studies have examined the clinicopathologic relationship between tumor infiltrating B lymphocyte and HSP70 expression in human cancer. So far, there is no complete knowledge on the relationship in oral squamous cell carcinoma (OSCC). The present study was conducted to evaluate the relationship between tumor infiltrating B lymphocyte and HSP70 expression in OSCC, as well as the clinical outcome.<i> Materials and Methods</i>. In this retrospective study, the immunohistochemical analysis of 50 OSCC specimens was performed using CD20 and HSP70 antibodies. The relationship between markers’ expression and clinicopathologic data was evaluated using Mann–Whitney test, Chi-square test, logistic regression model, and Spearman’s correlation coefficient.<i> Results</i>. The data analysis showed significant correlation between peritumoral CD20<sup>+</sup> B lymphocyte infiltration and lymph node metastasis (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M1" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g></svg></span>). Furthermore, HSP70 expression was significantly correlated with stage (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M2" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g></svg></span>), lymph node metastasis (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M3" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg></span>), and tumor size (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M4" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-53"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-53"/></g></svg></span>). However, no relationship was observed between B lymphocyte infiltration and HSP70 expression.<i> Conclusion</i>. The results suggest that peritumoral B lymphocyte infiltration and HSP70 expression level have significant association with OSCC and may be considered as prognostic indicators in OSCC. Thus, evaluation of B cells as therapeutic targets in OSCC patients is recommended.

Nasim Taghavi

Zhaleh Mohsenifar

Alireza Akbarzadeh Baghban

Alireza Arjomandkhah

CD20+ Tumor Infiltrating B Lymphocyte in Oral Squamous Cell Carcinoma: Correlation with Clinicopathologic Characteristics and Heat Shock Protein 70 Expression

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance<i> (ABC)</i> phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the<i> ABC</i> phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of<i> ABC</i> phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of<i> ABC</i> phenomenon with no toxicity to other organs.

Tamara C. M. Lopes

D&#xe9;bora F. Silva

Walyson C. Costa

Fr&#xe9;d&#xe9;ric Fr&#xe9;zard

Jos&#xe9; M. Barichello

Neila M. Silva-Barcellos

Wanderson G. de Lima

Simone A. Rezende

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver

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Pathology Research International