Immunohistochemistry For E-cadherin Research Articles

Evaluation of e-cadherin expression in gastric cancer as a prognostic marker

Introduction: Carcinoma of stomach is a common malignancy and globally stands at fourth position frequency- wise. E-cadherin, is a major cell adhesion molecule, the loss of which gives rise to invasive and metastatic properties to the cancer cells. Aim of the Study: To study the E-cadherin expression in gastric carcinomas by immuno-histochemistry and to correlate its pattern of staining with tumor differentiation, invasion, histological variants, and lymph node status. Materials and Methods: A two year prospective study was done from September 2011 to August 2013 at Kakatiya Medical College and MGM Hospital, Warangal. The resected specimens of stomach and endoscopic biopsy specimens taken from carcinoma stomach in this study period were considered. Routine histopathology and immunohistochemistry for E-cadherin were done on the sections. Results: 60 cases were studied of which 26 were gastric biopsies and 34 were gastrectomy specimens. The patient age ranged from 41-72 years and the male to female ratio was 1.6:1. There were 70% and 30% cases that showed intestinal type and diffuse type morphology respectively. Preserved E-cadherin was mainly seen in intestinal type tumors 14/42 (33.33%) with grade 3 staining, while majority of diffuse adenocarcinomas 8/18 (44.44%) were negative for E-cadherin staining. Higher stage tumors and poorly differentiated adenocarcinomas showed reduced E-cadherin staining. Cases with positive lymph nodes 22/29(75.86%) had diminished / absent E-cadherin staining. Conclusion: Normal gastric mucosa on IHC shows strong membranous E-cadherin positivity. There is a gradual decrease in intensity and percentage, and the pattern changes towards cytoplasmic staining in gastric carcinomas. Keywords: Gastric carcinoma, E –Cadherin expression, Prognostic markers, Immunohistochemistry.

Could E-Cadherin and CD10 Expression be Used to Differentiate Between Atypical Endometrial Hyperplasia and Endometrial Carcinoma?

Endometrial carcinoma contributes to morbidity and mortality among female individuals worldwide. The role of E-cadherin expression, as an adhesion molecule, in endometrial carcinoma is controversial. Moreover, the role of CD10-expressing stromal cells in endometrial carcinoma is still unclear. The aim of this work was to evaluate E-cadherin and CD10 expression in normal endometrium, atypical endometrial hyperplasia, and endometrial carcinoma, and assess their role to differentiate atypical endometrial hyperplasia from endometrial carcinoma. The association of E-cadherin and CD10 expression with clinicopathologic parameters of endometrial carcinoma was also determined. This retrospective study was carried out on 80 cases including 36 cases of endometrial adenocarcinoma (all were of endometrioid type), 34 cases of atypical endometrial hyperplasia, and another 10 cases of normal endometrial tissue. Immunohistochemistry for E-cadherin and CD10 was conducted. The studied patients were in their sixth and seventh decades of life with a mean age of 60.97 yr. Most of the carcinoma cases (18 cases) were grade 1, 10 cases were grade 2, and only 2 cases were grade 3. With regard to International Federation of Gynecology and Obstetrics (FIGO) staging, 28 cases were stage I, and only 2 cases were stage II. E-cadherin in normal endometrial tissue and atypical hyperplastic endometrial tissue showed predominantly membranous homogenous reactivity, and CD10 was detected as membranocyptoplasmic staining. However, we noticed the subcellular change of E-cadherin reactivity to be heterogenous and predominantly membranocytoplasmic in endometrial carcinoma, whereas CD10 remained membranocytoplasmic. Concerning E-cadherin expression, there was a statistically significant relationship between E-cadherin expression, tumor grade and FIGO staging, whereas there was an insignificant relationship between E-cadherin expression and patients' age, specimen type, tumor gross pattern, and histopathologic types. With regard to CD10 expression, there was a statistically significant relation between CD10 expression and tumor grade and FIGO staging with insignificant relation with patients' age, tumor gross pattern, specimen type, and tumor histologic types (villoglandular vs. usual endometrial adenocarcinoma). There was also a highly statistically significant positive relationship between E-cadherin expression and CD10 expression. This study puts the spot light on their role in differentiating between atypical endometrial hyperplasia and endometrial carcinoma, which is often difficult.

MUC1 and E-cadherin immunohistochemistry of endometrium cannot predict the outcome of in vitro fertilization: A case-control study

Background: Although in vitro fertilization (IVF) has played a major role in the management of infertility, its failure rate is still 60-80% and most of the causes failure are unknown. Therefore, a histomorphology-based predictive tool to forecast IVF outcome that utilizes expression data of certain cellular adhesion molecules in endometrium pertaining to successful implantation might provide the theoretical basis to develop a low-cost laboratory investigation suited for low to middle income countries as opposed to the expensive gene expression based tools like endometrial receptivity array. In this study, mucin 1 (MUC1) and E-cadherin immunohistochemistry of endometrium from aspiring IVF women were analyzed to see if there is any correlation between signal intensities and endometrial receptivity in terms of IVF outcome. Methods: This was a case-control study conducted among women of reproductive age with infertility who underwent IVF at the Centre for Assisted Reproduction (CARe), Dhaka between March and December 2017. Endometrial biopsy samples were collected and routine histological as well as immunohistochemical analysis was performed on those samples at the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. A total of 21 patients, 17 cases (IVF failure) and four controls (IVF success), were included in the study by consecutive convenient sampling. Relevant history and medical records of each of the patients were also obtained accordingly. Results: No statistically significant correlation was found between IVF outcomes and the signal intensities in endometrium produced by MUC1 and E-cadherin immunohistochemistry. Conclusions: Despite the fact that this study did not find any statistically significant correlation between endometrial immunohistochemistry of MUC1 and E-cadherin and IVF outcome, further studies may incorporate gene expression arrays to supplement or revise those findings.

10 A VARIANT OF CHOLERA TOXIN B SUBUNIT ENHANCES COLON EPITHELIAL WOUND HEALING VIA AN UNFOLDED PROTEIN RESPONSE

Cholera toxin B subunit (CTB) exhibits multifaceted biological activity in the mucosa via binding to GM1 ganglioside on intestinal epithelial cells. We recently found that a recombinant variant of CTB, which contains an artificial KDEL endoplasmic reticulum (ER) retention signal (CTB-KDEL), induces mucosal healing in a mouse dextran sodium sulfate (DSS) acute colitis model. The objectives of this study are to investigate CTB-KDEL’s epithelial wound repair mechanism and characterize its efficacy in preclinical models. We hypothesize that CTB-KDEL’s wound healing effect is mediated through ER retention within epithelial cells, thereby facilitating mucosal healing in IBD. The effects of CTB-KDEL, CTB and G33D-CTB-KDEL (a non-GM1-binding variant) were analyzed for cell migration, subcellular localization, an unfolded protein response (UPR) and TGFβ expression in Caco2 cells. In a DSS acute colitis model, C57BL/6J mice were gavaged with a single dose of CTB-KDEL, CTB or PBS at the end of 7-day DSS exposure. An optimal dosing regimen of CTB-KDEL was evaluated in mice exposed to repeated DSS cycles. Efficacy was measured on the basis of colon length, Disease Activity Index, histopathological scoring, E-cadherin immunohistochemistry and wound healing gene/cytokine expression in the colon. For ex vivohuman colonic explant experiments, colon tissues were obtained from consenting IBD patients who underwent total colectomy, which were cultured with CTB-KDEL, CTB or a PBS for 24 hours. Caco2 cell migration was enhanced by CTB-KDEL at concentrations of 0.3 – 3 μM, while CTB and G33D-CTB-KDEL failed to show such an effect. CTB-KDEL showed longer residence in the ER than CTB, leading to the activation of UPRs, particularly the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) arm, and subsequent TGFβ signaling in Caco2 cells. In the acute colitis model, CTB-KDEL, but not CTB, facilitated recovery from colonic damage as evident in macroscopic and histological evaluations, with significant upregulation of wound healing genes and E-cadherin positive staining in the colon (Fig. 1). Weekly oral administration of 3 μg CTB-KDEL showed significant efficacy against established colitis in the chronic DSS model. In human IBD colon explants, CTB-KDEL at 1 μM induced significant upregulation of the IRE1/Xbp1 pathway as well as wound healing genes including TGFB1and the E-cadherin gene CDH1, along with the retention of viable crypts in the colon. The results demonstrated CTB-KDEL’s unique colon epithelial wound healing activity via a UPR, providing implications for new IBD treatment strategies.

Potential Oncogenic Role and Prognostic Implication of MicroRNA-155-5p in Oral Squamous Cell Carcinoma.

Altered microRNA expression is associated with cancer progression. This study investigated the prognostic significance of microRNA-155-5p (miR-155-5p), a well-known oncomiR, in oral squamous cell carcinoma (OSCC). miR-155-5p expression was assessed using quantitative reverse-transcription polymerase chain reaction in 68 formalin-fixed, paraffin-embedded OSCC specimens. E-Cadherin immunohistochemistry was conducted to correlate epithelial-mesenchymal transition (EMT) with miR-155-5p expression. Elevated miR-155-5p was associated with higher pathological TNM stage (p=0.048) and relapse (p=0.029). High miR-155-5p expression, along with angiolymphatic invasion and advanced stage, was a statistically significant prognostic factor for poorer disease-free survival. In patients with stage I-II disease, high miR-155-5p was the only significant prognostic factor (p=0.033). A significant negative correlation was observed between miR-155-5p and E-cadherin expression (p=0.015), suggesting a possible role for miR-155-5p in EMT. miR-155-5p expression might contribute to EMT-associated OSCC progression and serve as a biomarker for predicting relapse, especially for patients with early-stage OSCC.

Differentiating breast carcinoma with signet ring features from gastrointestinal signet ring carcinoma: assessment of immunohistochemical markers

Signet ring morphology is recognized throughout the gastrointestinal tract. However, this pattern may be observed in other primary sites giving rise to diagnostic challenges in the work-up of metastases. Relatively newer immunohistochemical markers have not been evaluated in this context. We assessed expression patterns of several common immunohistochemical markers in tumors with Signet ring morphology to delineate a pragmatic approach to this differential diagnosis. Primary breast and gastrointestinal carcinomas showing Signet ring features were reviewed. Non-mammary and non-gastrointestinal tumors with this morphology were included for comparison. Estrogen receptor (ER), progesterone receptor (PR), E-cadherin, CK7, CK20, GCDFP-15, mammaglobin, CDX2, GATA-3, and HepPar-1 immunohistochemistry was performed. Expression patterns were compared between breast and gastrointestinal tumors as well as lobular breast and gastric tumors. Ninety-three cases were identified: 33 breast carcinomas including 13 lobular, 50 gastrointestinal tumors including 23 gastric, and 10 from other sites. ER (sensitivity=81.8%, specificity=100%, positive predictive value (PPV)=100%, negative predictive value (NPV)=89.3%) and GATA-3 (sensitivity=100%, specificity=98%, PPV=96.8%, NPV=100%) expression were associated with breast origin. CK20 (sensitivity=66.7%, specificity=93.3%, PPV=94.1%, NPV=63.6%) and CDX2 (sensitivity=72%, specificity=100%, PPV=100%, NPV=68.9%) demonstrated the strongest discriminatory value for gastrointestinal origin. These markers exhibited similar discriminatory characteristics when comparing lobular and gastric signet ring carcinomas. In a limited trial on metastatic breast and gastric cases, these markers successfully discriminated between breast and gastric primary sites in 15 of 16 cases. ER and GATA-3 are most supportive of mammary origin and constitute an effective panel for distinguishing primary breast from primary gastrointestinal Signet ring tumors when combined with CK20 and CDX2 immunohistochemistry.

Immunohistochemical evaluation of prime molecules in cervical lesions towards assessment of malignant potentiality.

A comparative immunohistochemical evaluation of p63, CD105, and E-cadherin expression pattern in histopathologically confirmed normal cervical epithelium (NCM), dysplastic cervical epithelium (DYS) and squamous cell carcinoma (SCC) of uterine cervix towards assessing malignant potentiality of the precancerous condition. The biopsies from cervical mucosa (normal, dysplasia, and cancer) were studied by routine hematoxylin and eosin (H and E) and by immunohistochemistry for p63, E-cadherin, and CD105 expression. The expressions of these molecules were assessed in a semiquantitative way by (i) counting p63 cell population and distribution, (ii) intensity scoring of E-cadherin along the expression path, and (iii) measuring CD105 expression density. p63+ cells were highest in carcinomas followed by dysplasia and normal. An abrupt increase in CD105 expression was observed through change of normal to dysplasia and cancer. A decrease in membranous E-cadherin expression was noticed in the transformation from normal to precancer and cancers. The malignant potential of the dysplastic conditions is likely to be correlated with upregulation in p63 and CD105 expression and a simultaneous downregulation of membranous E-cadherin.

Cell Polarity Reversal Distinguishes True Micropapillary Growth From Retraction Artifact in Invasive Urothelial Carcinoma.

Focal micropapillary features in invasive urothelial carcinoma is sometimes difficult to distinguish from retraction artifact morphologically. Cell polarity reversal has been demonstrated in micropapillary tumors by epithelial membrane antigen (EMA) immunostaining. We have previously described the use of E-cadherin as a cell polarity marker in ovarian micropapillary serous borderline tumors. The aim of this study was to evaluate the utility of immunohistochemistry for EMA and E-cadherin in differentiating micropapillary urothelial carcinoma from retraction artifact. We identified 29 invasive urothelial carcinomas with micropapillary features and 30 invasive urothelial carcinomas without reported micropapillary features but with areas of retraction artifact. Cell polarity reversal was considered present if E-cadherin showed membranous apical cup-like staining or if EMA demonstrated a well-defined basal staining towards the stroma. Twenty-seven of 29 cases (93%) of urothelial carcinoma with micropapillary features demonstrated EMA or E-cadherin staining patterns consistent with cell polarity reversal. Staining consistent with micropapillary architecture was identified with both markers in 20 of these 27 cases (74%). Six cases showed reversal of polarity by E-cadherin alone, whereas 1 case showed polarity reversal by EMA alone. Retraction artifacts showed circumferential staining by E-cadherin and lacked well-defined basal staining by EMA. Three cases originally classified as with retraction artifact showed reversal of cell polarity by both EMA and E-cadherin and were reclassified as micropapillary. Our data show that pathologists can reliably make this distinction in most cases. However, in some cases with ambiguous features, EMA and E-cadherin immunostaining may aid in resolving this diagnostic dilemma.

Microsatellite Alterations and Protein Expression of 5 Major Tumor Suppressor Genes in Gastric Adenocarcinomas

PURPOSE: In gastric adenocarcinoma (GC), the major tumor suppressor genes (TSGs) such as p16, PTEN, Rb, E-cadherin, and p53, may play important roles in various regulatory pathways and in tumor suppression. This study evaluated the loss of heterozygosity (LOH) of microsatellite and protein expression of 5 TSGs and the results were examined for their correlation with clinicopathological factors. METHODS: LOH analysis was carried out using polymerase chain reactions with 15 polymorphic microsatellite markers of 5 chromosomes containing TSGs in 100 surgically resected tumors. Protein expression was evaluated by immunohistochemistry (IHC). RESULTS: LOH was detected in 83% of GCs. LOH of 9p21, 10q23, 13q14, 16q22, and 17p13 were detected in 26%, 31%, 24%, 22%, and 35% of cases, respectively. Protein expression of p16, PTEN, Rb, E-cadherin, and p53 were found to be 31%, 39%, 28%, 32%, and 46% of cases. Advanced GCs showed significantly higher rates of 17p13 LOH and p53 expression. 9p21 LOH and E-cadherin IHC were correlated with higher tumor grade. Lymph node metastasis was correlated with the LOH of 9p21, 16q22, and 17p13 and IHC of the Rb and p53. A higher stage was correlated with 10q23 and 17p13 in LOH and p53 for IHC. CONCLUSION: These results suggest that LOH and protein expression of various TSGs are important in carcinogenesis and tumor invasion. Additionally, LOH and IHC may be useful clinical indicators for determining the prognosis of patients with GCs. In particular, the 17p13 LOH and p53 for IHC can be applied as simple evaluations in the clinic.

Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation.

This study aimed to elucidate the impact of epithelial regenerative responses and immune cell infiltration on biliary complications after liver transplantation. Bile duct (BD) damage after cold storage was quantified by a BD damage score and correlated with patient outcome in 41 patients. Bacterial infiltration was determined by fluorescence in situ hybridization (FISH). BD samples were analyzed by immunohistochemistry for E-cadherin, cytokeratin, CD56, CD14, CD4, CD8, and double-immunofluorescence for cytokine production and by messenger RNA (mRNA) microarray. Increased mRNA levels of adherens junctions (P < 0.01) were detected in damaged BDs from patients without complications compared with damaged BDs from patients with biliary complications. Immunohistochemistry showed increased expression of E-cadherin and cytokeratin in BDs without biliary complications (P = 0.03; P = 0.047). FISH analysis demonstrated translocation of bacteria in BDs. However, mRNA analysis suggested an enhanced immune response in BDs without biliary complications (P < 0.01). Regarding immune cell infiltration, CD4+ and CD8+ cells were significantly increased in patients without complications compared with those with complications (P = 0.02; P = 0.01). In conclusion, following BD damage during cold storage, we hypothesize that the functional regenerative capacity of biliary epithelium and enhanced local adaptive immune cell infiltration are crucial for BD recovery. Such molecular immunological BD analyses therefore could help to predict biliary complications in cases of "major" epithelial damage after cold storage.Liver Transplantation 23 1422-1432 2017 AASLD.

Colorectal signet ring cell carcinoma: Influence of EGFR, E-cadherin and MMP-13 expression on clinicopathological features and prognosis.

Signet ring cell carcinoma (SRCC) is unique rare subtype of mucin-producing colorectal adenocarcinoma characterized by presence of signet ring cells, in >50% of the tumor tissue. This study aims to investigate expression of EGFR, E-cadherin and MMP-13 expression on clinicopathological features of signet ring cell type and its prognostic effect using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal cancer cases among which 19 cases of SRCC. High density manual tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for EGFR, E-cadherin and MMP-13 expression was done. We found that SRCC was significantly associated with younger age and more frequency of LN metastasis than all other groups. SRCC was also significantly associated with annular gross picture, more depth of invasion, advanced stage, more lymphovascular emboli, more perineural invasion and less arousal from an overlying adenoma. In conclusion, colorectal SRCC has distinctive clinicopathological and histological features with different unique mechanisms of carcinogenesis and more aggressive biologic behavior than other colorectal carcinoma subtypes. Negative/low expressions of EGFR and E-cadherin and MMP-13 were found in SRCC with no effect on the prognosis.

Brief fixation enables same-day breast cancer diagnosis with reliable assessment of hormone receptors, E-cadherin and HER2/Neu

AimsPreoperative core needle biopsy (CNB) is commonly used to confirm the diagnosis of breast cancer. For treatment purposes and for determining histological type, especially in case of neoadjuvant therapy, oestrogen...

Molecular characterization of CD44+/CD24-/Ck+/CD45- cells in benign and malignant breast lesions.

Breast cancer epithelial cells with the CD44+/CD24-/low phenotype possess tumor-initiating cells and epithelial-mesenchymal transition (EMT) capacity. Massive parallel sequencing can be an interesting approach to deepen the molecular characterization of these cells. We characterized CD44+/CD24-/cytokeratin(Ck)+/CD45- cells isolated through flow cytometry from 43 biopsy and 6 mastectomy samples harboring different benign and malignant breast lesions. The Ion Torrent Ampliseq Cancer Hotspot panel v2 (CHPv2) was used for the identification of somatic mutations in the DNA extracted from isolated CD44+/CD24-/Ck+/CD45- cells. E-Cadherin and vimentin immunohistochemistry was performed on sections from the corresponding formalin-fixed, paraffin-embedded (FFPE) blocks. The percentage of CD44+/CD24-/Ck+/CD45- cells increased significantly from non-malignant to malignant lesions and in association with a significant increase in the expression of vimentin. Non-malignant lesions harbored only a single-nucleotide polymorphism (SNP). Mutations in the tumor suppressor p53 (TP53), NOTCH homolog 1 (NOTCH1), phosphatase and tensin homolog (PTEN), and v-akt murine thymoma viral oncogene homolog 1 (AKT1) genes were found in isolated CD44+/CD24-/Ck+/CD45- cells from ductal carcinomas in situ (DCIS). Additional mutations in the colony-stimulating factor 1 receptor (CSF1R), ret proto-oncogene (RET), and TP53 genes were also identified in invasive ductal carcinomas (IDCs). The use of massive parallel sequencing technology for this type of application revealed to be extremely effective even when using small amounts of DNA extracted from a low number of cells. Additional studies are now required using larger cohorts to design an appropriate mutational profile for this phenotype.

Value of E-cadherin and desmin immunohistochemistry in distinguishing metastatic adenocarcinoma from reactive mesothelial hyperplasia in serous effusion

Value of E-cadherin and desmin immunohistochemistry in distinguishing metastatic adenocarcinoma from reactive mesothelial hyperplasia in serous effusion

Progressive development of endometriosis and its hindrance by anti-platelet treatment in mice with induced endometriosis

We have recently shown that platelets drive smooth muscle metaplasia (SMM) and fibrogenesis in endometriosis through epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). To see whether this is true in vivo, this prospective, randomized, and serially evaluated mouse investigation was conducted. Endometriosis was induced in female Balb/C mice, which were then randomly divided into two groups: Tanshinone IIA (TAN) and control (CTL) groups. TAN mice were treated with TAN but CTL mice received none. Every week until the 6th week after induction, five mice from each group were killed. Lesion weight was measured and lesion samples were subjected to immunohistochemistry and histochemistry analysis of platelet aggregation (CD41), E-cadherin, TGF-β1, phosphorylated Smad3, α-SMA, collagen I, CCN2, LOX, desmin and SM-MHC, and the extent of fibrosis was evaluated by Masson trichrome staining. It was found that endometriotic lesions exhibited progressive cellular changes consistent with the progressive EMT, FMT, SMM, and fibrogenesis. TAN treatment resulted in significant hindrance of EMT, FMT, SMM and fibrogenesis, and reduced lesion weight (all P-values <0.05). These data corroborate the notion that endometriotic lesions undergo progressive EMT and FMT, giving rise to SMM and ultimately fibrosis. This understanding sheds new light onto the natural history of endometriosis.

PD-L1 expression is associated with epithelial-to-mesenchymal transition in adenocarcinoma of the lung

PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy for pulmonary adenocarcinoma (pADC). Epithelial-to-mesenchymal transition (EMT) is involved in the progression and immune evasion of cancers. Therefore, we investigated the association between PD-L1 expression and EMT phenotype in pADC. Immunohistochemistry for E-cadherin (epithelial marker), ZEB1, SNAIL, SLUG, vimentin (mesenchymal markers), PD-L1, CD8, and PD-1 was performed on 477 cases of pADC. Cases were classified into epithelial, mesenchymal, epithelial-mesenchymal, and unspecified types based on immunohistochemical results. PD-L1 expression was scored as 0 in 14.0% (n=67), 1 in 26.4% (n=126), 2 in 51.2% (n=244), and 3 in 8.4% (n=40). PD-L1 score was positively correlated with SNAIL and vimentin H scores (P<.001, both). After dichotomizing patients into PD-L1-negative and PD-L1-positive groups, PD-L1 positivity was significantly higher in patients with mesenchymal (71.2%; 84/118) and epithelial-mesenchymal (62.7%; 84/134) phenotypes compared with those with epithelial (50.6%; 44/87) and unspecified (50.0%; 35/70) phenotypes (P=.005). The significant association between PD-L1 expression and EMT phenotype was maintained in EGFR-mutated pADCs. Moreover, cases with EMT phenotype (ie, mesenchymal and epithelial-mesenchymal) were infiltrated by higher numbers of CD8+ and PD-1+ cells than those with epithelial and unspecified phenotypes in EGFR-mutated pADCs (P=.043 for CD8+ cells and P<.001 for PD-l+ cells). Particularly, cases with EMT phenotype and PD-L1 expression showed the greatest amount of CD8+ and PD-1+ cells in EGFR-mutated cases (P=.043 for CD8+ cells and P=.005 for PD-1+ cells). This study demonstrates that EMT phenotype is related to PD-L1 overexpression in pADC cells and patients with EMT-phenotype pADC may benefit from PD-1/PD-L1-blocking immunotherapy.

The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice.

BackgroundThe gut microbiota is now known to play an important role contributing to inflammatory-based chronic diseases. This study examined intestinal integrity/inflammation and the gut microbial communities in sedentary and exercising mice presented with a normal or high-fat diet.MethodsThirty-six, 6-week old C57BL/6NTac male mice were fed a normal or high-fat diet for 12-weeks and randomly assigned to exercise or sedentary groups. After 12 weeks animals were sacrificed and duodenum/ileum tissues were fixed for immunohistochemistry for occludin, E-cadherin, and cyclooxygenase-2 (COX-2). The bacterial communities were assayed in fecal samples using terminal restriction fragment length polymorphism (TRFLP) analysis and pyrosequencing of 16S rRNA gene amplicons.ResultsLean sedentary (LS) mice presented normal histologic villi while obese sedentary (OS) mice had similar villi height with more than twice the width of the LS animals. Both lean (LX) and obese exercise (OX) mice duodenum and ileum were histologically normal. COX-2 expression was the greatest in the OS group, followed by LS, LX and OX. The TRFLP and pyrosequencing indicated that members of the Clostridiales order were predominant in all diet groups. Specific phylotypes were observed with exercise, including Faecalibacterium prausnitzi, Clostridium spp., and Allobaculum spp.ConclusionThese data suggest that exercise has a strong influence on gut integrity and host microbiome which points to the necessity for more mechanistic studies of the interactions between specific bacteria in the gut and its host.

Is the Wnt/β catenin signalling pathway activated in Seminoma?: An immunohistochemical study.

The loss of reduction of some adhesion molecules is associated with the invasive phenotype of carcinomas. The aim of this paper was to study the expression of some proteins related to the Wnt/β catenin signalling pathway in seminomas by immunohistochemical techniques in order to assess the contribution of this pathway to the tumoral development. Immunohistochemistry for E-cadherin, β-catenin, vimentin, C-Myc, cyclin D1 (CD1) and placental alkaline phosphatase. (PALP) was carried out in 24 archival tissue blocks of seminomas. Two cellular lines were used as E-cadherin and β-catenin controls. (JKT-1 and TCam-2). E-cadherin was positive in two seminomas and in one carcinoma in situ. (CIS), showing a membranous pattern. βcatenin was principally expressed in Sertoli cells, in some malignant gonocytes of CIS and in the membranes of seminomatous cells. No β-catenin immunostaining was detectable in the cytoplasm and the nuclei of neoplastic cells. Seminomas were weakly possitive for vimentin in 11/24 cases. None of the tumors displayed expression of C-Myc or CD1. The results does not indicate the activation of the Wnt pathway, due to the lack of vimentin expression in 13/24 seminomas, the low expression in the rest of the cases, the lack of β-catenin in nuclei and the absence of CD1 and C-Myc expression. Further work is needed to confirm these observations and to test other signaling pathways in seminomas.

E-cadherin immunohistochemistry in breast pathology: uses and pitfalls.

E-cadherin immunohistochemistry is used commonly in surgical pathology practice to help distinguish lobular carcinoma in situ from ductal carcinoma in situ and invasive lobular carcinoma from invasive ductal carcinoma in histologically problematic or indeterminate cases. However, the interpretation of E-cadherin immunostains is not always straightforward. Failure to recognize the pitfalls and limitations of E-cadherin immunostains can lead to an erroneous diagnosis which may result in inappropriate patient management, particularly for patients with in-situ lesions. In this paper we review the uses and, particularly, the pitfalls in the interpretation of E-cadherin immunostains in distinguishing lobular from ductal lesions of the breast.

Dual use of E-cadherin and D2-40 immunostaining in unusual meningioma subtypes.

Meningiomas usually can be readily diagnosed on H&E alone, although occasionally immunohistochemistry (IHC) confirmation is desirable. Studies exploring the diagnostic utility of either podoplanin (D2-40) or E-cadherin IHC in meningiomas have conflicted, and no studies exist in which the two IHCs have been used in combination for diagnosis. E-cadherin and D2-40 IHC was performed on 77 meningiomas (31 ordinary; eight microcystic; four rare myxoid; six metaplastic; six invasive of orbit, muscle, and/or soft tissue; two metastatic; six brain-invasive World Health Organization [WHO] grade II, nine non-brain-invasive WHO grade II; and five anaplastic WHO grade III), with semi-quantitative scoring on a three-tier scale (0, focal [1+], strong/diffuse [2+]). All meningiomas were either E-cadherin or D2-40 IHC+, with 69 of 77 showing dual immunostaining, most at the 2+ level. No downregulation of E-cadherin IHC was found in invasive or high-grade meningiomas. Dual E-cadherin/D2-40 IHC can supplement diagnosis of meningioma.