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

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shahid Pervez ◽  
Sidra Arshad ◽  
Brooj Abro
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Staining Pattern ◽  
Antigen Expression ◽  
Gastric Epithelium ◽  
P Value ◽  
Structural Differentiation ◽  
Membrane Staining ◽  
Poorly Differentiated ◽  
Well Differentiated

Aim. 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. Methods. 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. Results. 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. Conclusion. 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.

CD44

2000 ◽  
Vol 124 (2) ◽  
pp. 212-215
Author(s):  
Lourdes R. Ylagan ◽  
John Scholes ◽  
Rita Demopoulos
Keyword(s):  
Staining Pattern ◽  
Squamous Differentiation ◽  
Normal Epithelium ◽  
Primary Tumors ◽  
Squamous Mucosa ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Tissue Specimens

Abstract Objective.—To test the hypothesis that CD44 standard (CD44[s]) and its other variants, CD44v6 and CD44v7-8, might be useful markers of squamous differentiation in epithelial tumors. Design.—We studied expression of CD44(s), CD44v6, and CD44v7-8 using immunohistochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, pancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplastic tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 33 adenosquamous tumors were used. All were stained with monoclonal antibodies against a conserved portion of CD44(s) and its variants, CD44v6 and CD44v7-8, using the avidin-biotin peroxidase method. Results.—CD44(s) and its variants consistently and strongly stained areas of tumors with well-developed squamous differentiation. These markers also consistently and strongly stained normal squamous mucosa. Reactivity for CD44 and its variants was lacking in normal glandular type epithelium and in adenocarcinomas composed entirely of well-differentiated mucin-producing glands. Areas of well-differentiated carcinoma, both squamous and adenocarcinoma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with well-differentiated squamous foci being consistently positive, well-differentiated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less intense with the variants, it followed the same staining pattern as found for CD44(s). No differences in the extent or intensity of staining were identified in the metastatic versus primary tumor foci, nor was any difference identified between superficial and deeply invasive areas of primary tumors. Conclusions.—Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epithelium and tumors, and that these markers can identify areas of well- to moderately differentiated elements in adenosquamous neoplasms. However, poorly differentiated tumors show an inconsistent staining pattern with CD44, such that it cannot be used as a reliable and practical marker of squamous differentiation in poorly differentiated neoplasms.

scholarly journals Morphological and immunohistochemical characterization of spontaneous endometriosis in rhesus macaques (Macaca mulatta)

2017 ◽  
Vol 4 (1) ◽  
pp. 77-91 ◽  
Author(s):  
Eva Gruber-Dujardin ◽  
Martina Bleyer ◽  
Kerstin Mätz-Rensing
Keyword(s):  
Epithelial Cells ◽  
Macaca Mulatta ◽  
Rhesus Macaques ◽  
Expression Profiles ◽  
Smooth Muscle Actin ◽  
Macroscopic Appearance ◽  
Somatic Markers ◽  
Different Types ◽  
Poorly Differentiated ◽  
Well Differentiated

Abstract. Several cases of spontaneous endometriosis in middle-aged to old rhesus macaques (Macaca mulatta) from the breeding colony of the German Primate Center were thoroughly characterized with regards to anatomical distribution and macroscopic appearance, histological differentiation and immunohistochemical profile including somatic markers, hormonal receptors, and proliferation indices. More than half of the examined animals (five of nine) were directly related to one breeding male, supporting a strong genetic predisposition. Histologically, four different types of endometriotic lesions, depending on the degree of ectopic endometrial gland and stromal differentiation (well differentiated, purely stromal, mixed differentiation, poorly differentiated), could be constantly identified within all animals. Immunohistochemistry (IHC) of cytokeratin (CK), vimentin, smooth muscle actin (SMA), desmin, estrogen (ER), and progesterone (PR) receptors as well as of the nuclear proteins Ki67 and p53 revealed varying staining patterns in the four different types of endometriosis differentiation and compared to normal endometrium. Purely stromal, mixed, or poorly differentiated lesions, especially, showed additional cytokeratin-positive stromal cells, whereas epithelial cells of endometriosis with mixed or poor differentiation increasingly expressed mesenchymal markers (vimentin, SMA). Hormonal receptor and Ki67 expression in well-differentiated endometriotic lesions mostly reflected that of normal endometrial tissue according to the cyclic phase of the animal, while the expression gradually diminished with decreasing grade of differentiation. However, increased nuclear accumulations of p53 antigen could only be continuously detected in epithelial cells of mixed or poorly differentiated endometriosis. Altogether, these findings support the pathogenetic theory of coelomic metaplasia, since the expression profiles of somatic markers in less differentiated forms closely resembled that of mesothelial cells. Thus, the four different histological types of endometriosis might display subsequent grades of differentiation in the course of time, with poorly differentiated types representing newly formed, immature lesions and well-differentiated types being older, fully differentiated forms, rather than being the outcome of dedifferentiation processes.

scholarly journals Correlation Between Tumor Cell Differentiation and CEA Levels in Patients with Adenocarcinoma of the Rectum

2020 ◽  
Vol 52 (4) ◽  
Author(s):  
Reno Rudiman ◽  
Kiki Lukman ◽  
Tubagus Izzul Barr
Keyword(s):  
Cell Differentiation ◽  
Tumor Cell ◽  
Histopathological Examination ◽  
P Value ◽  
Stage Iiic ◽  
Serum Cea ◽  
Poorly Differentiated ◽  
The Mean ◽  
Well Differentiated ◽  
Tumor Cell Differentiation

Adenocarcinoma of the rectum is the most common colorectal cancer in Indonesia. This cancer has the highest recurrence after curative surgical therapy with or without adjuvant therapy. With the advancing modern histopathology and molecular biology, the prognosis after therapy can be predicted through surveillance using tumor cell differentiation and carcinoembryonic antigen (CEA). The aim of this study was to analyze the correlation between tumor cell differentiation and serum CEA level in patients with adenocarcinoma of the rectum in Dr. Hasan Sadikin General Hospital Bandung, Indonesia. This was a retrospective observational analytic study conducted from January 2018- January 2019. There were 36 patients involved in this study consisting of 3 patients (8.3%) diagnosed with Stage II, 10 patients (27.7%) with Stage IIIA, 20 patients (55.5%) with stage IIIB, and 3 patients (8.3%) with stage IIIC. On histopathological examination, it was demonstrated that19 patients (52.8%) were well-differentiated, 15 patients (41.7%) were moderately differentiated, and 2 patients (5.6%) were poorly differentiated. The mean CEA level (CI 95%) for well-differentiated patients before surgery was 138.18 (15.99-260.38) ng/ml while the same level for the moderately differentiated patients was 64.34 (34.34-163.02) ng/ml. The mean CEA level for poorly differentiated patients was 1.55 (6.71-9.81) ng / ml. The result of the Kruskal Wallis test showed a p-value of 0.004. There is a strong correlation between the level of tumor cell differentiation and CEA level.

Na-K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells

2007 ◽  
Vol 292 (1) ◽  
pp. G124-G133 ◽  
Author(s):  
Sigrid A. Rajasekaran ◽  
Sonali P. Barwe ◽  
Jegan Gopal ◽  
Sergey Ryazantsev ◽  
Eveline E. Schneeberger ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Tight Junctions ◽  
Protein Phosphatase ◽  
Mammalian Cells ◽  
Protein Phosphatase 2A ◽  
Epithelial Cell Line ◽  
Phosphatase 2A ◽  
Apical Junctions ◽  
Well Differentiated

Tight junctions are crucial for maintaining the polarity and vectorial transport functions of epithelial cells. We and others have shown that Na-K-ATPase plays a key role in the organization and permeability of tight junctions in mammalian cells and analogous septate junctions in Drosophila. However, the mechanism by which Na-K-ATPase modulates tight junctions is not known. In this study, using a well-differentiated human pancreatic epithelial cell line HPAF-II, we demonstrate that Na-K-ATPase is present at the apical junctions and forms a complex with protein phosphatase-2A, a protein known to be present at tight junctions. Inhibition of Na-K-ATPase ion transport function reduced protein phosphatase-2A activity, hyperphosphorylated occludin, induced rearrangement of tight junction strands, and increased permeability of tight junctions to ionic and nonionic solutes. These data suggest that Na-K-ATPase is required for controlling the tight junction gate function.

Motility of leukemic lymphocytes

1990 ◽  
Vol 48 (3) ◽  
pp. 368-369
Author(s):  
Manoj Raje ◽  
Karvita B. Ahluwalia
Keyword(s):  
Quantitative Data ◽  
Laser Doppler Velocimetry ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Cellular Space ◽  
Differentiated Cells ◽  
Poorly Differentiated ◽  
Solid Tissues ◽  
Well Differentiated ◽  
Reduced Mobility

In Acute Lymphocytic Leukemia motility of lymphocytes is associated with dissemination of malignancy and establishment of metastatic foci. Normal and leukemic lymphocytes in circulation reach solid tissues where due to in adequate perfusion some cells get trapped among tissue spaces. Although normal lymphocytes reenter into circulation leukemic lymphocytes are thought to remain entrapped owing to reduced mobility and form secondary metastasis. Cell surface, transmembrane interactions, cytoskeleton and level of cell differentiation are implicated in lymphocyte mobility. An attempt has been made to correlate ultrastructural information with quantitative data obtained by Laser Doppler Velocimetry (LDV). TEM of normal & leukemic lymphocytes revealed heterogeneity in cell populations ranging from well differentiated (Fig. 1) to poorly differentiated cells (Fig. 2). Unlike other cells, surface extensions in differentiated lymphocytes appear to originate by extrusion of large vesicles in to extra cellular space (Fig. 3). This results in persistent unevenness on lymphocyte surface which occurs due to a phenomenon different from that producing surface extensions in other cells.

HER2 OVEREXPRESSION IN ENDOSCOPIC BIOPSY SAMPLE OF GASTRIC ADENOCARCINOMA BY IMMUNOHISTOCHEMISTRY

2012 ◽  
pp. 109-118
Author(s):  
Viet Nho Le ◽  
Van Huy Tran ◽  
Cong Thuan Dang ◽  
Van To Ta
Keyword(s):  
Gastric Adenocarcinoma ◽  
Undifferentiated Carcinoma ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Endoscopic Biopsy ◽  
Her2 Overexpression ◽  
Tubular Adenocarcinoma ◽  
Signet Ring ◽  
Poorly Differentiated ◽  
Well Differentiated

Background and aim: HER2 overexpression by immunohistochemistry is a prognostic maker in gastric cancer and helps to select candidates benefitted from targeted therapy with trastuzumab. This study is aimed at the assessing HER2 overexpression and its relationship with endoscopic and histopathological findings of gastric adenocarcinoma. Objectives and methods: Biopsy samples from 92 gastric cancer patients were examined for HER2 status by immunohistochemical staining. Results: 6.5% of tumors were cardia tumors and 93.5% were non-cardia tumors. Using the Lauren classification, 51.1% were intestinal type and 48.9% were diffuse type. Using WHO classification, 54.3% were tubular adenocarcinoma, 7.6% were mucinous adenocarcinoma, 15.2% were signet-ring cell carcinoma, and 22.8% were undifferentiated carcinoma. 32.6% were well-differentiated, 15.2% were moderately-differentiated, and 52.2% were poorly-differentiated carcinoma. HER2 was positive in 20.7% of gastric carcinomas, 50% cardia tumors and 18.6% non-cardia tumors. HER2 positivity among polypoid, fungating, ulcerated, and infiltrative types were 38.5%, 29.7%, 9.1% and 0%, respectively. HER2 overexpression in intestinal type was higher than that in diffuse type (31.9% vs. 8.9%, p = 0.009). HER2 overexpression in tubular adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and undifferentiated carcinoma was 28.0%, 14.3%, 7.1% and 14.3%, respectively. HER2 overexpressions were different between differentiation degrees: 30% of well-differentiated tumors, 35.7% moderately-differentiated tumors, and 10.4% of poorly-differentiated tumors (p = 0.037). Conclusions: HER2 overexpression was found in 20.7% of endoscopic biopsy sample of gastric adenocarcinoma and was associated with endoscopic gross characteristic, Lauren histologic type and differentiation degree.

scholarly journals Cutaneous squamous cell carcinoma arising in hidradenitis suppurativa: A case report

2019 ◽  
Vol 7 ◽  
pp. 2050313X1984735 ◽  
Author(s):  
Catherine F Roy ◽  
Simon F Roy ◽  
Feras M Ghazawi ◽  
Erica Patocskai ◽  
Annie Bélisle ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hidradenitis Suppurativa ◽  
Rare Complication ◽  
Excisional Biopsy ◽  
Necrosis Factor Alpha ◽  
Spindle Cells ◽  
Poorly Differentiated ◽  
Well Differentiated

We present a case of a 64-year-old man who presented with a rapidly growing tumor in the left buttock and intergluteal cleft area, which was affected by hidradenitis suppurativa. The patient was on tumor necrosis factor-alpha inhibitors for hidradenitis suppurativa for 2 years prior to the development of the mass. Initial biopsy of the mass showed a well-differentiated squamous cell carcinoma with spindle cells and positive epithelial immunomarkers. Subsequent excisional biopsy of the tumor showed an infiltrating poorly differentiated squamous cell carcinoma composed of islands of atypical sarcomatoid spindle cells. Squamous cell carcinoma arising in hidradenitis suppurativa is a rare complication which may occur secondary to chronic inflammation and epidermal hyperproliferation in hidradenitis suppurativa–affected areas.

Tight Junctions of Human Uterine Epithelial Cells Change during the Menstrual Cycle: A Morphometric Study

1992 ◽  
Vol 144 (1) ◽  
pp. 36-38 ◽  
Author(s):  
C.R. Murphy ◽  
P.A.W. Rogers ◽  
M.J. Hosie ◽  
J. Leeton ◽  
L. Beaton
Keyword(s):  
Menstrual Cycle ◽  
Epithelial Cells ◽  
Tight Junctions ◽  
Morphometric Study ◽  
Uterine Epithelial Cells

scholarly journals 752 The impact of grade of differentiation and BRAF mutation status on neoantigen and immune landscape in papillary thyroid cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A800-A800
Author(s):  
Myungwoo Nam ◽  
Myungwoo Nam ◽  
Woojung Yang ◽  
Ju Young Lee ◽  
Jaeyoun Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Braf Mutation ◽  
Cytolytic Activity ◽  
Activity Score ◽  
Cyt B ◽  
Mutation Status ◽  
Poorly Differentiated ◽  
Immune Traits ◽  
Well Differentiated

BackgroundThe use of immune checkpoint inhibitors (ICIs) in cancer treatment has been approved by the FDA, but its application is experimental in the treatment of papillary thyroid cancer (PTC). Induction of immune response via recognition of neoantigens is considered to be the basis for the treatment mechanism of ICIs.1 However, the neoantigen landscape has not been explored in PTC. Our aim is to investigate the immune landscape of PTC in relation to neoantigens, taking into account the BRAF mutation status and grade of differentiation as contributing factors.MethodsBRAF V600E mutation status and thyroid differentiation scores (TDSs) were gathered from the PTC cohort of The Cancer Genome Atlas (TCGA). TDS was derived from the mRNA expression levels of 16 thyroid function genes to quantify the grade of differentiation. Tumors with TDSs in the 1st quartile and 4th quartile were defined as poorly differentiated and well differentiated, respectively. The neoantigen burden for each sample was predicted using CloudNeo pipeline. The infiltration of immune cells was calculated through CIBERSORT.ResultsAmong 400 patients with predicted neoantigen data, 187 (47%) had BRAF mutations. The BRAF mutated tumors showed increased cytolytic activity score (CYT, p=0.001), increased infiltration of regulatory T cells (Treg, p<0.001), and higher PD-L1 expression (p<0.001) compared to BRAF wild-type tumors (figure 1). In regard to grade of differentiation, poorly differentiated tumors showed increased CYT (p=0.002), increased infiltration of Treg (p<0.001), and higher PD-L1 expression (p<0.001) compared to well differentiated tumors (figure 2). However, BRAF mutation status or grade of differentiation did not correlate with the neoantigen burden. Also, the neoantigen burden did not show any correlations with immune landscape features such as infiltration of CD8+ T cells or Treg, CYT, and PD-L1 expression.Abstract 752 Figure 1Immune traits according to BRAF mutation status. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.Abstract 752 Figure 2Immune traits according to grade of differentiation. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.ConclusionsIncreased CYT and higher expression of PD-L1 in the BRAF mutated or the poorly differentiated tumors imply the possible role of ICI use in these subgroups of patients. However, the immune response to these subgroups does not seem to be mediated through the increase in neoantigen formation. Further studies are warranted to explore markers for immunotherapy implication.ReferencesSchumacher TN, Schreiber RD, Neoantigens in cancer immunotherapy. Science 2015; 348:69–74.

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