GLUT1 Expression in Cutaneous Sebaceous Lesions Determined by Immunohistochemical Staining Patterns

GLUT1 is a membrane associated carrier protein that functions in the physiologic transport of glucose across cell membranes. Multiple studies have shown an increased GLUT1 expression in various tumor types and a role in cancer prognosis. The aim of this study was to determine whether cutaneous sebaceous lesions have a differential expression of GLUT1 by immunohistochemistry (IHC). GLUT1 IHC was performed on excision specimens of ten cases of sebaceous carcinoma, nine of sebaceoma, ten of sebaceous adenoma, and ten of sebaceous hyperplasia. Intense, diffuse cytoplasmic staining was observed in sebaceous carcinoma. The pattern of GLUT1 staining in sebaceomas and sebaceous adenomas consisted of a gradient of intense cytoplasmic staining in the basaloid cells with a decreased intensity to membranous staining only and absent staining in mature sebaceous cells. In lesions of sebaceous hyperplasia, GLUT1 staining outlined the basal layer of each gland; cytoplasmic staining was minimal to absent. Increased cytoplasmic staining of GLUT1 may correlate with cellular metabolic and proliferative activity. GLUT1 has potential utility in differentiating sebaceous lesions.

Histopathological spectrum of lower Gastro-intestinal colonoscopic biopsy lesion with special reference to Her-2/neu expression in carcinoma colon

Cancer associated with colon is one of the principal risk factors from decease in women and men. Although importance growing aspect of human epidermis receptor2 (Her2) as a therapeutic target is rising its role as a biomarker in the form of predicting indicator within colorectal Cancer (CRC)is still a mystery. Present research is undertaken for evaluating the Her2/neu description in Cancer of the colon. This research comprises 256patientswith spectrum of histopathological treatment ranging from colitis to colorectal carcinoma at our department between 2015- 2017. Her2/neu Immunohistochemistry was done in the colorectal carcinoma and scores based on Ruschoff et al. Her-2 testing in gastric cancer. Out of a total number of 256 cases enrolled in our study group, the majority belonged to the age group of 40-60 years, with M: F ratio being 1.4:1. The commonest site of the lesion occurred in the rectum (43.75%) followed by ascending colon and caecum (12.08%). Non neoplastic lesions constituted about two third of all cases, the commonest being inflammatory bowel disease(21.48%). In benign neoplastic lesions of tubular adenoma was the commonest type, and in malignant commonest type was colorectal adenocarcinoma NOS(64.44%) followed by mucinous adenocarcinoma (22.22%). Because of more prominent membranous staining observed in high grade colorectal cancers, Her2neu expression is found to be an important predictive marker of carcinoma colon, especially the adenocarcinoma, NOS. Like Breast carcinoma, target oriented therapy can be instituted especially in Her 2/neu positive high grade and metastatic tumors.

Sinonasal FUS-ERG-Rearranged Ewing’s Sarcoma Mimicking Glomangiopericytoma

Ewing’s sarcoma is a rare and aggressive tumor that typically arises in the long bones of the extremities. It belongs in the family of small round blue cell tumors and is characterized immunohistochemically by diffuse CD99 expression and molecularly by one of several oncogenic translocations, most commonly t(11;22)(q24;q12) between the <i>EWSR1</i> gene and the <i>FLI1</i> gene. Here we present a rare case of Ewing’s sarcoma in the sinonasal tract with <i>FUS-ERG</i> gene arrangement that was regarded for almost a decade as a sinonasal-type hemangiopericytoma (glomangiopericytoma). This case illustrates the surprisingly prolonged natural history of Ewing’s sarcoma that did not receive therapy for many years and the importance of considering alternative genetic translocations. Our experience suggests that the presence of diffuse CD99 membranous staining pattern in a small blue round cell tumor with morphology typical for Ewing’s sarcoma but FISH negative for <i>EWSR1</i> rearrangement should prompt consideration of <i>FUS-ERG</i> fusion.

p-120 Catenin is a Useful Diagnostic Biomarker for Distinguishing Plasmacytoid and Sarcomatoid Variants From Conventional Urothelial Carcinoma

Context.— Plasmacytoid urothelial carcinoma (PC-UC) is an aggressive variant of urothelial carcinoma (UC), characterized by loss of E-cadherin (E-Cad)–mediated intercellular adhesion. Loss of E-Cad by immunohistochemistry can help diagnosis PC-UC; however, sensitivity is limited. Expression of other cadherin-catenin adhesion complex members, that is, p-120 catenin (p-120) and β-catenin (B-Cat), which are diagnostically useful for lobular breast carcinoma, remains unknown in UC. Objective.— To determine the utility of p-120 and B-Cat in conventional and variant UC. Design.— E-cadherin, B-Cat, and p-120 immunohistochemistry was performed in 25 conventional UCs and 33 variant UCs, including 22 PC-UCs, 6 sarcomatoid UCs (SUCs), and 5 micropapillary UCs. Membranous staining for all biomarkers was considered normal; however, any cytoplasmic staining or an absence of staining was considered diagnostically abnormal. Next-generation sequencing was performed on 8 PC-UC cases. Results.— E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17 of 22; 77%) with an additional 2 of 22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21 of 22 cases (95%). Most SUCs showed an absence of E-Cad (5 of 6; 83%) and cytoplasmic or negative p-120 in 5 of 6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive. Conclusions.— p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC.

The potential diagnostic value of immunohistochemical expression of trop2 in papillary thyroid carcinoma

Background The diagnosis of the papillary thyroid carcinoma depends upon the characteristic histopathological features, however there may be borderline cases with controversial features necessitating the use of immunohistochemical studies.Trophoblastic cell surface antigen 2 (TROP-2) is a promising marker that is used recently in the diagnosis of PTC. Aim of the Work To highlight the diagnostic value of TROP-2 marker in PTC in comparison with other benign and borderline thyroid lesions on tissue specimens. Materials and Methods This retrospective cohort study included 55 cases of PTC, its histopathological variants, benign and borderline thyroid lesions received at pathology department, Faculty of medicine, Ain Shams university between 2011 and 2016. Immunohistochemical evaluation of TROP-2 was applied on. Membranous staining without cytoplasm in &gt; 5% of cells was considered positive. TROP-2 expression in various thyroid lesions were determined by immunohistochemical staining and results were statistically analyzed. Results Among the studied cases, 85.1% of PTC demonstrated TROP-2 staining. Most of the cases revealed diffuse staining. No significant staining difference was reported between studied classic and non classic variants. TROP-2 sensitivity and specificity were 85.1% and 94.4%. Conclusion In view of present study we concluded the use of TROP-2 as a novel promising marker in the diagnosis of PTC as its positivity was significantly higher in PTC compared to all other non PTC lesion .

Programmed Death Ligand 1 Expression in Laryngeal Squamous Cell Carcinomas and Prognosis

Aim: We aimed to show the immunohistochemical expression of programmed death ligand 1 (PD-L1) in laryngeal squamous cell carcinomas (SCCs). Materials and methods: The study includes 52 laryngeal SCC cases that underwent surgical resection. Immunohistochemical staining of PD-L1 (Clone 22C3) was applied to the sections obtained from paraffin blocks. Combined Positive Score (CPS) was evaluated as described in manuals. Tumor Proportion Score (TPS) was assessed by the percentage of positive tumor cells which were designated as positive if ⩾1% of the tumor cells showed membranous staining. Results: There were 35 cases (67.3%) having CPS < 1 and 17 cases (32.7%) having CPS ⩾ 1. There was no relationship between CPS, TPS, and the clinicopathological data. Conclusion: Further studies with a large number of advanced-stage cases are needed.

High Expression of Trophoblast Cell Surface Antigen 2 in Triple-negative Breast Cancer Identifies a Novel Therapeutic Target

Objectives Patients with triple-negative breast cancer (TNBC) respond poorly to current therapeutic modalities. The newly FDA-approved drug conjugate, Sacituzumab Govitecan, targeting antitrophoblastic cell surface antigen 2 (Trop-2), offers a new modality to treat these subtypes of breast carcinoma (BC). Our study examines expression of Trop-2 by immunohistochemistry (IHC) in TNBC. Methods Forty cases of TNBC were selected from our files (34 ductal, 4 pleomorphic lobular, 1 metaplastic, and 1 mixed ductal and lobular carcinoma). A control group included 11 luminal A-like, 11 luminal B-like, and 8 HER2-like BC. Immunostaining for Trop-2 was performed on 4-micron-thick tissue sections using goat polyclonal antibody (R&D Systems). Three pathologists individually scored the % and intensity of membranous staining. The % of staining was defined as <10%, 10%-50%, and >50%. The intensity of staining was scored as 3+ (crisp circumferential membranous staining), 2+ (medium membranous staining), 1+ (patchy weak membranous staining), and 0 (no staining). A Kruskal-Wallis H-test and pairwise comparison with Bonferroni correction was performed to compare % and intensity of staining in TNBC to control group. Results TNBC exhibited stronger Trop-2 staining in both intensity and extent when compared to the control. The result was significantly different, χ2 (4) = 17.427, P = .001. A pairwise comparison with Bonferroni correction found significant difference between TNBC (42.55) and luminal A (16.65) (P < .001). There was significant agreement (P < .001) among 3 independent pathologists for assessing % and intensity of staining. Conclusion The extent and intensity of staining for Trop-2 is higher in TNBC than in other molecular subtypes of BC. These findings suggest that patients with TNBC may potentially benefit from this targeted therapy. Furthermore, identification of Trop-2 in other molecular subtypes may expand the therapeutic potential of this new drug. Further studies are needed to determine the efficacy of this marker.

Delta-like Protein 3 Prevalence in Small Cell Lung Cancer and DLL3 (SP347) Assay Characteristics

Context.— Delta-like protein 3 (DLL3) is a protein that is implicated in the Notch pathway. Objective.— To present data on DLL3 prevalence in small cell lung cancer and staining characteristics of the VENTANA DLL3 (SP347) Assay. In addition, the assay's immunoreactivity with other neoplastic and nonneoplastic tissues is outlined. Design.— Individual formalin-fixed, paraffin-embedded specimens of small cell lung cancer and tissue microarrays comprising neoplastic and nonneoplastic tissues were procured. Sections were cut and stained with DLL3 (SP347) assay. The slides were examined to determine prevalence, staining characteristics, and immunoreactivity. Results.— Cytoplasmic and/or membranous staining was observed in 1040 of 1362 specimens of small cell lung cancer (76.4%). Homogenous and/or heterogeneous and partial and/or circumferential granular staining with varied intensities was noted. Immunoreactivity was also observed in other neoplastic and nonneoplastic tissues. Conclusions.— Our study findings provided the profile of DLL3 staining characteristics that can be used for determining the level of DLL3 expression in small cell lung cancer.

IMMUNOHISTOCHEMICAL EXPRESSION OF THE PROMISING THERAPEUTIC TARGET (HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2/NEU) IN IRAQI PATIENTS WITH MEDULLOBLASTOMA

Objectives: With the advent of ongoing novel modalities toward the treatment of human epidermal growth factor receptor 2 (HER2)/NEU - positive malignancies, the serious side effects of chemoradiotherapy have been minimized. Hence, this study was conducted to identify the patterns of immunohistochemical expression of the promising therapeutic target (HER2/NEU) among Iraqi patients with medulloblastoma in an attempt to provide basic histological information’s that would help in future clinical researches.Materials and Methods: In this retrospective study, 42 formalin - fixed paraffin - embedded tissue blocks represent cases of surgically removed medulloblastomas were retrieved from the archived materials in a specialized surgical hospital at Bagdad. The histological diagnosis had been revised, and all cases were stained by the immunohistochemical technique with HER2/NEU antibody and assessed independently by three pathologists.Results: Out of 42 cases, only two which represent 4.76% showed positive results manifested by a strong membranous staining when immunohistochemically evaluated using the same scoring system established for HER2/NEU in breast cancer. 14 cases (33.3%) showed incomplete membranous and five cases (11.9%) showed only cytoplasmic reaction patterns.Conclusion: The rate of expression of HER2/NEU in medulloblastoma among Iraqi patients is very low and found only in aggressive anaplastic histological type when immunohistochemically evaluated using the same scoring system established for HER2/NEU in breast cancer. However, a good number of negative cases showed cytoplasmic and incomplete membranous staining patterns highlighting the importance of establishing medulloblastoma - specific HER2/NEU scoring criteria and testing methods to discover the unique feature of expression of this therapeutic target in medulloblastoma.

Impact and correlation of mutational load (ML) and specific mutations (mts) assessed by limited targeted profiling (LTP) with PD-L1 tumour expression (exp) in resected non-small cell lung carcinoma (NSCLC).

11587 Background: The advent of immunotherapy represents a paradigm shift in the treatment of NSCLC compared to conventional chemotherapy. Recent studies have shown higher mts burden assessed by exome sequencing are associated with improved objective response and clinical benefit. We performed this study to evaluate the impact of ML assessment by LTP, correlating with PD-L1 exp and clinicopathological variables in resected NSCLC. Methods: NSCLC patients(pts) who underwent curative resection between 1998 and 2006 at our institution were included. PD-L1 status was assessed using Ventana SP124 antibody on archival FFPE surgical tumour specimens cores. PD-L1 was scored positive if membranous staining was present in >1% of tumour cells aggregated across the replicate cores to address heterogeneity. In collaboration with the Lung Cancer Genomics Ireland Study a targeted panel of 49 genes were assessed by Sequenom MassArray including genes in MAPK and PI3K pathways. Clinical data was obtained from hospital electronic database. Results: Ninety-one pts were included, of which 51 (56.0%) were males, with a median age of 65 years (range: 42 – 82). 51.6%, n=47 with squamous histological subtypes, 46.2%, n=42 were ex-smoker and 49.5%, n=45 had Stage I disease. 23.1%, n=21 had PD-L1 positivity. 149 mts were identified of which, 32(21.5%) with PHLPP2, 31(20.9%) with PIK3R1 and 21(14.1%) with TP53. The presence of PI3K and TP53 mts are associated with positive PD-L1 status (see table). An inverse correlation of PD-L1 positivity with ML of (1 vs 2 vs 3: 53.8% vs 30.8% vs 15.4%) was noted. Conclusions: We did not identify higher PD-L1 exp with higher ML assessed by a LTP widely used in clincial practice. However, positive PD-L1 exp was correlated with PIK3R1 and TP53 mts , warranting further investigation as potential modulators or surrogates of positve PD-L1 expression. [Table: see text]