Positive Expression Of CD44 Research Articles

Immunohistochemical expression of CD44 in invasive breast carcinoma

Background: In India, breast cancer forms the most common malignancy, accounting for 28.2% of all female cancers. Breast cancer consists of phenotypically diverse group of diseases. Due to different relapse abilities, doubling times, and different infiltrative capacities, it is important to identify potential biomarkers that could be used to screen high-risk patient and predict breast cancer prognosis in conjunction with classical pathological parameters. Aims and Objectives: The present study was conducted to evaluate immunohistochemical expression of CD44 in breast carcinoma and to correlate CD44 expression with other clinicopathological parameters and molecular classification of carcinoma breast. Materials and Methods: The present study was a prospective descriptive study conducted on 100 cases of carcinoma breast diagnosed on modified radical mastectomy specimens that were submitted to the Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, over the period of 2 years. Results: Out of 100, 64 cases (64%) were CD44 positive. Out of these 64 cases, 9 (9%) cases were 1+, 34 (34%) cases were 2+, and 21 (21%) cases showed 3+ positive expression of CD44 in tumor cells. Loss of CD44 expression was seen in 36 (36%) cases. A statistically significant association of CD44 was seen with multifocality of the tumor, negative estrogen receptor/progesterone receptor (ER/PR) expression, and molecular subtypes. No statistically significant association of CD44 was seen with age, side of tumor, lymph node metastasis, lymphovascular invasion, ductal carcinoma in situ and Ki67, and HER2neu expression. Conclusion: A high CD44 expression in breast carcinoma correlates with aggressive tumor characteristics such as multifocality, negative ER/PR expression, and belonging to the basal subtype which is associated with poor prognosis. Conversely, low CD44 expression is linked to Luminal A and Luminal B subtypes which have good prognosis. These indicate the role of CD44 as a prognostic biomarker in the carcinoma breast.

CD34+stromal cells/telocytes and their role in mouse lung development: Light microscopy, immunofluorescence, ultrastructural and scanning electron microscopy evidence.

Telocytes (TCs), a novel type of mesenchymal or interstitial cell with specific, very long and thin cellular prolongations, have been found in various mammalian organs and have potential biological functions. However, their existence during lung development is poorly understood. This study aimed to investigate the existence, morphological features, and role of CD34+ SCs/TCs in mouse lungs from foetal to postnatal life using primary cell culture, double immunofluorescence, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The immunofluorescence double staining profiles revealed positive expression of CD34 and PDGFR-α, Sca-1 or VEGFR-3, and the expression of these markers differed among the age groups during lung development. Intriguingly, in the E18.5 stage of development, along with the CD34+ SCs/TCs, haematopoietic stem cells and angiogenic factors were also significantly increased in number compared with those in the E14.5, E16.5, P0 and P7. Subsequently, TEM confirmed that CD34+ SCs/TCs consisted of a small cell body with long telopodes (Tps) that projected from the cytoplasm. Tps consisted of alternating thin and thick segments known as podomers and podoms. TCs contain abundant endoplasmic reticulum, mitochondria and secretory vesicles and establish close connections with neighbouring cells. Furthermore, SEM revealed characteristic features, including triangular, oval, spherical, or fusiform cell bodies with extensive cellular prolongations, depending on the number of Tps. Our findings provide evidence for the existence of CD34+ SCs/TCs, which contribute to vasculogenesis, the formation of the air‒blood barrier, tissue organization during lung development and homoeostasis.

A case study of a liver transplant-treated patient with glycogen storage disease type Ia presenting with multiple inflammatory hepatic adenomas: an analysis of clinicopathologic and genetic data

BackgroundGlycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay.Case presentationHere, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES).WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother.Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of β-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive.This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation.After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred.ConclusionThe patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.

Surgical treatment of intracranial epithelioid hemangioendothelioma: a case report

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular neoplasm with an intermediate pattern of malignancy between benign neoplasms and angiosarcomas. Only 46 cases of intracranial localization of primary EHE in adults have been published.Case report: A 47-year-old male patient developed pronounced speech disorder of sensory and amnestic aphasia type, right-sided pyramidal hemiparesis within 3–4 days. Magnetic resonance imaging revealed a delimited left sided brain islet neoplasm with signs of hemorrhage and small perifocal edema. Intraoperatively, the neoplasm was represented by a conglomerate of pathologic vessels, with involvement of the terminal branches of the M2 segment of the middle cerebral artery, which prevented radical resection of the neoplasm. Based on histopathological and immunohistochemistry analysis of the neoplasm (positive expression of CD31, CD34, proliferative activity index Ki-67 10%) the morphologic diagnosis of EHE was established. 3 months after surgery, continued growth of the residual part of the neoplasm was noted. Temozolomide chemotherapy was clinically ineffective. The patient died due to the development of dislocation syndrome after 9 months.Discussion. The malignant characteristics of EHE include invasive growth, recurrence, and metastasis, which is more common in intracranial localization of the neoplasm. If EHE is suspected, radical surgical removal of the neoplasm should be sought.

Thoracic SMARCA4-deficient tumors: a clinicopathological analysis of 52 cases with SMARCA4-deficient non-small cell lung cancer and 20 cases with thoracic SMARCA4-deficient undifferentiated tumor.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a distinct clinicopathological entity with an aggressive clinical course. Additionally, SMARCA4/BRG1 deficiency can be observed in a few patients with non-small cell lung cancer (NSCLC). We aimed to compare the clinicopathological, immunohistochemical and prognostic features of SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) with those of thoracic SMARCA4-UT. Patients with BRG1-deficient tumors in the lung or thorax were enrolled in the study from the Department of Pathology of West China Hospital, Sichuan University, from January 2014 to June 2022. We retrospectively collected the clinicopathological and immunohistochemical features and outcomes of these patients. Seventy-two patients had tumors in the lung or thorax with BRG1-deficient expression, including 52 patients with SMARCA4-dNSCLC and 20 patients with thoracic SMARCA4-UT. Among the patients with SMARCA4-dNSCLC, 98.1% were male, 85.7% were smokers, and 79.5% (35/44) had tumor-node-metas-tasis (TNM) III-IV tumors. Among the patients with thoracic SMARCA4-UT, all were males who smoked, and 93.75% (15/16) had TNM III-IV tumors. Pure solid architecture and necrosis were the predominant pathological features. Rhabdoid morphology was observed in some SMARCA4-dNSCLCs (10/52, 19.2%) and thoracic SMARCA4-UTs (11/20, 55%). In most patients with thoracic SMARCA4-UT, the tumors exhibited scattered weak expression or negative expression of epithelial markers, and positive expression of CD34 and Syn. Overall survival (OS) and progression-free survival (PFS) were not significantly different between patients with SMARCA4-dNSCLC and patients with thoracic SMARCA4-UT (p = 0.63 and p = 0.20, respectively). Thoracic SMARCA4-DTs include SMARCA4-dNSCLC and thoracic SMARCA4-UT. Both have overlapping clinicopathological features and poor prognosis. We hypothesize that thoracic SMARCA4-UT may be the undifferentiated or dedifferentiated form of SMARCA4-dNSCLC. However, further studies with larger cohorts and longer follow-up periods are needed.

The Correlation between VEGF and CD34 Protein Marker and Pyogenic Granuloma.

A typical non-neoplastic connective tissue proliferations called a pyogenic granuloma. A vascular adhesion molecule used to assess angiogenesis is the CD34 marker. The primary memberof a family of growth factors, VEGF helps in generating and maintaining the lymphatic and blood circulation systems. The aim of the study was to know the correlation between VEGF and CD34 protein marker and pyogenic granuloma. Thirty-one formalin fixed paraffin embedded (FFPE) blocks were taken from female pyogenic granuloma patients ranging in age from 29 to 70. The IHC was used to identify VEGF and CD34 expression in the cytoplasm of the cells. Seventeenout of 31 patients had VEGF positive expression. Twenty-sixout of 31 had CD34 positive expression and 5 with no expression (negative expression). Brown-stained cytoplasm showed high VEGF and CD34 expression, whereas blue stained cytoplasm showed no VEGF and CD34 expression in these cells. The results suggest the role of suchbiomarkers in the oral pyogenic granuloma pathogenesis, and it appears that CD34 and VEGF are valuable biomarkers in evaluating vascular and inflammatory diseases like pyogenic granuloma.

Evaluation of CD44 Expression in Prostatic Adenocarcinoma: An Institutional Study.

Prostate adenocarcinomais the second-most common cause of cancer. Globally, many cancer-related deaths among men were noted due to prostate adenocarcinoma. CD44 plays a key role in mediating cell-to-cell and cell-to-matrix interaction, which further helps to maintain the integrity of tissue and also inhibits tumor metastasis. Cross-sectional study was done on chips from transurethral resections of the prostate (TURP) and prostatic core biopsy specimens. All specimens with clinically diagnosed and histopathologically confirmed prostatic adenocarcinoma were included in the study. Prostatic intraepithelial neoplasia (PIN), recurrent cases, and patients who had undergone radiotherapy/ chemotherapy prior to biopsy were excluded from the study. The sample size for the current study was 57 with an 8% prevalencevalue, 95% confidence interval, and 8% absolute error. Immunoreaction to CD44 antibody is membranous and was evaluated by calculating positively stained cell percentage and stainingintensity. These two parameters were added to obtain a final score; a score of 0-3 was considered as negative, and a score of 4-6 was regarded as positive. A statistically significant difference was only found between Gleason grade (p<0.001), clinical staging (p<0.002), nodal metastasis (p<0.015), and distant metastasis (p<0.020) with CD44 positive expression. The rest of the parameters like PSA (p=0.642) and age (p=0.051) did not correlate with CD44-positive expression. Out of 29 cases with positive CD44 expression, 100% positivity was seen in Gleason's grades 1,2, and 3. This indicates that CD44 expression showed lesser positivity in poorly differentiated carcinoma. CD44 positivity was seen in 83.3% in the T2 stage. An inverse relationship between tumor staging and CD44 expression was observed with positive CD44 expression in lower tumor staging which implies loss of CD44 expression was associated with greater tumor aggressiveness. Lymph node metastasis cases showed more negative CD44 expression (59.5%) and the same was noted in patients without distant metastasis, that is in 61% of the subjects. Conclusion: Cells tend to lose the ability of CD44 expression as they progress from well-differentiated adenocarcinoma to poorly differentiated adenocarcinoma. CD44 expression suggests that the tumor is in a well-differentiated and gland-forming state as compared to Gleason's grade. Loss of CD44 expression suggests tumor aggressiveness. Thus, the upregulation of CD44 expression can be considered as a potential target for targeted therapy. As many targeted and gene therapies are in clinical trials, large-scale multicentered studies are needed for a better understandingof the clinical course of the disease.

Isolation and Characterization of Porcine Endocardial Endothelial Cells.

The heart contains diverse endothelial cell types. We sought to characterize the endocardial endothelial cells (EECs), which line the chambers of the heart. EECs are relatively understudied, yet their dysregulation can lead to various cardiac pathologies. Due to the lack of commercial availability of these cells, we reported our protocol for isolating EECs from porcine hearts and for establishing an EEC population through cell sorting. In addition, we compared the EEC phenotype and fundamental behaviors to a well-studied endothelial cell line, human umbilical vein endothelial cells (HUVECs). The EECs stained positively for classic phenotypic markers such as CD31, von Willebrand Factor, and vascular endothelial (VE) cadherin. The EECs proliferated more quickly than HUVECs at 48 h (1310 ± 251 cells vs. 597 ± 130 cells, p = 0.0361) and at 96 h (2873 ± 257 cells vs. 1714 ± 342 cells, p = 0.0002). Yet EECs migrated more slowly than HUVECs to cover a scratch wound at 4 h (5% ± 1% wound closure vs. 25% ± 3% wound closure, p < 0.0001), 8 h (15% ± 4% wound closure vs. 51% ± 12% wound closure, p < 0.0001), and 24 h (70% ± 11% wound closure vs. 90% ± 3% wound closure, p < 0.0001). Finally, the EECs maintained their endothelial phenotype by positive expression of CD31 through more than a dozen passages (three populations of EECs showing 97% ± 1% CD31+ cells in over 14 passages). In contrast, the HUVECs showed significantly reduced CD31 expression over high passages (80% ± 11% CD31+ cells over 14 passages). These important phenotypic differences between EECs and HUVECs highlight the need for researchers to utilize the most relevant cell types when studying or modeling diseases of interest.

Combined expression of WT1/PRAME genes and BIRC5/PRAME genes and their clinical significance in adult patients with acute myeloid leukemia

Abstract Background Several tumor-associated antigens have been recently recognized that qualify to monitor tumor burden of acute myeloid leukemia (AML) or are used as antigen-specific approach for anticancer immunotherapy. Aim The current study was designed to assess the intracellular expression levels of the immunogenic tumor antigens ( WT1 , BIRC5, and PRAME genes) and clarify the prognostic effect of their combined overexpression, that is, WT1 /PRAME and BIRC5 / PRAME , on the clinical course, the outcome, and the response to treatment in patients with AML. Settings and design A total of 61 patients with AML were included in the study. All patients received induction chemotherapy. Detection of intracellular WT1, BIRC5, and PRAME genes in myeloid blast cells was done by real-time PCR on bone marrow samples. Their levels were correlated with the demographic data, the clinical and pathological data, the defined subgroups, the overall survival, and the response to treatment in patients with AML. Results WT1, BIRC5, and PRAME overexpression was detected in 73.8, 28, and 38.6% of patients, respectively. Nearly half of the patients (51.7%) were WT1+/PRAME− and significantly associated with absence of both favorable cytogenetic prognosis and complete remission. In addition, it expression was correlated with female sex, higher count of blasts in peripheral blood, positive CD34 expression, and higher FAB classification (M4) but with no statistically significant difference. Most patients were double negative BIRC5−/PRAME− (45.6%). A significant relation was found between BIRC5+/PRAME− and older age patients (P=0.003) and a lower overall survival (P=0.005) and also associated with higher count of blast cells but not statistically significant. Most BIRC5−/PRAME+ (72.7%) achieved complete remission at 28 days, followed by double negative BIRC5−/PRAME− (56.6%) at 28 days, most of BIRC5+/PRAME− patients died (77.8%). Conclusion In patients with AML, the expression levels of genes WT1, BIRC5, and PRAME were high, and these genes had a substantial correlation with poor prognostic factors, including a poor cytogenetic prognosis, incomplete remission, and a reduced survival rate. Therefore, they could be considered as targets for anticancer immunotherapy as well as possible markers for monitoring AML.

Clinico-Histomorphological Spectrum and CD34 in Gastro-Intestinal Stromal Tumours: An Experience from Tertiary Care Centre, Kolkata, India

Introduction: Gastrointestinal Stromal Tumours (GISTs) are an important subcategory of mesenchymal tumours of gastrointestinal tract. The discovery of c-kit mutation in a subset of GIST has made amenable the treatment of this entity by targeted therapy. Although, Cluster of Differentiation 34 (CD34) is a well established marker aiding in diagnosis of GIST, recent development of novel markers like Discovered on GIST1 (DOG1), CD117 have undermined its value. Still it’s a frequently used marker in the resource poor settings. Aim: To study the expression of CD34 immunomarker with respect to site, grade, stage, histomorphological type and risk category of GIST specimens received in the stipulated time period. Materials and Methods: An observational retrospective crosssectional was conducted in the Department of Pathology at R G Kar Medical College and Hospital, Kolkata, West Bangal, India. The duration of the study was three years and 11 months, from September 1, 2019 to August 31, 2022. All the samples diagnosed as GISTs within the study period, were taken from the received specimens in the department and immunohistochemical examination was done on the selected samples using monoclonal antibodies against CD34 after obtaining thin sections from formalin fixed paraffin embedded blocks and retrieval of antigen. The data was interpreted by light microscopy using a semiquantitative method with respect to prefixed parameters, where 50% proportional positivity of CD34 in the tumour cells was considered as positive. The data was analysed using Statistical Package for Social Sciences (SPSS) version 25.0. Results: Mean age of the study participants was 49.78 years. A total of 8 (34.7%) cases originating from stomach and 13 (56.5%) from intestine. Eight out of 23 (34.7%) cases showed positive expression of the marker. Six out of eight cases of gastric GISTs were found to be positive and 66.6% cases of high grade GISTs were positive for CD34. Statistically significant association was found between expression of CD34 and the site of tumour;-GISTs arising from stomach, particularly of spindle cell type, showing strong expression (p=0.003). It was found that, high grade GISTs are more likely to be positive for CD34. None of the epithelioid GISTs have shown positivity, neither any significant association was evident between expression of this marker with tumour stage or risk category. Conclusion: GISTs arising from stomach, particularly of spindle cell type, are more likely to show strong CD34 expression. Higher grade GISTs were found to be associated with positive CD34 expression in the present study, but no significant association was evident between expression of this marker.

CD133 is an independent predictive and prognostic marker in metastatic breast cancer

CD133 is a transmembrane glycoprotein and is considered the most common cell surface marker to identify cancer stem cells in hematological and solid tumors, including breast cancer. To evaluate the impact of immunohistochemical expression of CD133 on response rate and survival in metastatic breast cancer, as well as to correlate it with various demographics and clinicopathological characteristics. One-hundred metastatic breast cancer patients were prospectively recruited at the Medical Oncology Department at South Egypt Cancer Institute during the period from January 2018 to January 2020. There was a statistically significant correlation between CD133 positive patients with various adverse clinicopathological parameters such as high grade (p= 0.013), higher tumor (p= 0.001), and nodal staging (p= 0.024) during a median follow-up time of 17 months. In addition, Cases with CD133 positive expression had a significantly lower survival time than those with negative expression (3-years OS 37.4% versus 85.5%, p= 0.024). Regarding the response rate, CD133 positive patients had a lower response rate than negative patients (50% versus 54%, p= 0.012). Positive CD133 is correlated with poor prognosis in metastatic breast cancer patients.

Overexpression of Metastasis-Associated in Colon Cancer 1-Antisense RNA 1 (MACC1-AS1) in Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits miR-145-5P and Promotes Chemotherapy Resistance of Colorectal Cancer

BMSCs have the potential of multipotent differentiation. This study aimed to investigate the interaction between MACC1-AS1 and miR-145-5P in BMSCs and their effect on chemotherapy resistance in colorectal cancer (CRC). BMSCs extracted from mouse marrow were transfected with MACC1-AS1 mimic, or MACC1-AS1 NC (control group). CRC cells were treated wtih gemcitabine and then co-cultured with BMSCs to measure cell viability and invasiveness by MTT and Transwell assay, along with analysis of the expression of MACC1, miR-145-5P, HGF, C-met, P-gp, and MRP. Successful isolation of BMSCs was confirmed by flow cytometry with positive expression of CD44, CD105, and CD90 (purity &gt; 95%). Functionally, overexpression of MACC1-AS1 in BMSCs increased CRC cell viability and invasion, attenuated the inhibitory effect of gemcitabine (p &lt; 0.05). Up-regulation of MACC1-AS1 (9.23±1.21) as demonstrated by RT-qPCR, resulted in a decline of miR-145-5P expression (4.23±1.22) in CRC cells (p &lt; 0.05). In addition, overexpression of MACC1-AS1 increased the expression of HGF, C-met, and multidrug resistance-associated proteins (P-gp, and MRP). In conclusion, overexpression of MACC1-AS1 in BMSCs inhibits miR-145-5P expression to promote colorectal cancer cell progression possibly via activating HGF/C-met pathway and inducing resistance to chemotherapy.

EXPRESSION OF CD44 AS A CANCER STEM CELL MARKER IN ORAL CANCER: A META-ANALYSIS STUDY

Various researches have shown that Cluster of Differentiation 44 (CD44) is one of the valued markers. As it plays an important role in tumor growth and metastasis but studies also suggest it as a cancer stem cell (CSC) marker in oral cancer (OC). Therefore, we aimed to explore association between the expression of CD44 and clinicopathological characteristics along with the OC prognosis.We conducted literature search through PubMed database (till October 22, 2020) to determine and evaluate the clinical and prognostic significanceof CD44 expression in OC patients. According to the inclusion criteria we finalized 9 studies with 867 OC cases. We found the positive expression of CD44 in advanced stages was prominently associated with reduced survival rate. Our analysis suggest that higher tumor expression of CD44 may predict poor survival in end staged OC patient.

Cancer Stem Cell Markers, CD44 and ALDH1, for Assessment of Cancer Risk in OPMDs and Lymph Node Metastasis in Oral Squamous Cell Carcinoma.

Tumour heterogeneity in oral cancer is attributed to the presence of cancer stem cells (CSCs). CSCs are the most migratory and metastatic cellular subpopulation within tumours. Assessment of CSC markers as significant predictors of lymph node metastasis may prove valuable in the clinical setting. Furthermore, analysis of this panel of putative stem cell markers in oral dysplasia may additionally inform of the likelihood for oral potentially malignant disorders (OPMDs) to progress to oral squamous cell carcinoma (OSCC). The present study aims to assess the significance of CSC markers in the progression of OPMDs to OSCC and assessment of lymph node metastasis in OSCC. CD44 and ALDH1 were assessed immunohistochemically in 25 normal, 30 OPMDs, and 24 OSCCs. CD44 is a membranous marker and ALDH1 is a cytoplasmic marker. The immunohistochemical expression of these markers were compared between OPMDs with and without dysplasia, as well as between low-risk and high-risk dysplasias. Similarly, expression was compared between OSCC with and without lymph node metastasis and among grades of OSCC. Positive CD44 expression was seen in all normal mucosal tissues. The expression decreased from normal epithelium to OPMDs but increased in OSCC. CD44 expression was positive in 21 cases of OSCC (87.5%) and reduced from well-differentiated to poorly differentiated OSCC. CD44 staining index was higher in OSCC without lymph node metastasis (3.59) when compared with OSCC with lymph node metastasis (1.33). There was a statistically significant difference observed in the ALDH1 staining index among three groups (p < 0.05), with highest expression seen in OSCC. Within OPMDs, the ALDH1 staining index was statistically higher in OPMDs with dysplasia as compared to OPMDs without dysplasia. Furthermore, the expression was higher in OPMDs with high-risk dysplasia when compared with low-risk dysplasia, but this was not statistically significant (p = 0.82). In conclusion, The CD44 positive population possesses properties of CSCs in head and neck carcinoma, and continuous shedding could be found after CD44 down-regulation. The present study reports differences in ALDH1 expression between OPMDs with and without dysplasia, dysplastic and non-dysplastic epithelia, and low-risk and high-risk dysplasia. These findings may suggest ALDH1 as a specific marker for dysplasia. CD44 demonstrated a difference in staining index in OSCC without lymph node metastasis versus OSCC with lymph node metastasis. These findings may suggest CD44 as a marker for lymph node metastasis. Both proteins may play key roles in the tumorigenicity of CSCs in OPMDs and OSCC.

Expression of CD44 in Tumor Tissue and Serum of Small Cell Lung Cancer and Its Clinical Prognostic Significance

背景与目的小细胞肺癌(small cell lung cancer, SCLC)是一种以增殖迅速、易早期远处转移和获得性治疗耐药为特征的高侵袭性恶性肿瘤，临床预后极差。研究发现干细胞标志物CD44与肿瘤复发转移及治疗抵抗有关，而有关CD44在SCLC患者中的表达及其临床预后意义研究不多。本研究拟通过检测SCLC患者肿瘤组织和血清中CD44的表达水平，初步探索其与患者临床特征的关系并评估其判断预后的临床价值。方法将本院47例初治SCLC患者肿瘤组织和血清标本配对，分别应用免疫组化法(immunohistochemistry, IHC)和酶联免疫吸附试验方法(enzyme-linked immunosorbent assay, ELISA)对CD44进行检测，分析其与患者临床特征及预后的关系。结果SCLC患者肿瘤组织和血清中均可检测到干细胞标志物CD44的表达，体能状态(performance status, PS)2分的患者肿瘤组织CD44阳性率明显高于PS 0分-1分的患者(85.71% vs 30%, P=0.017)，根据化疗疗效对患者进行分组，疾病进展组肿瘤组织CD44免疫组化得分及血清CD44浓度均明显高于疾病控制组且差异均达到统计学意义(P=0.006, P=0.034)，单因素分析肿瘤组织CD44阳性患者无进展生存期(progression-free survival, PFS)较CD44阴性患者PFS明显缩短(5.23个月vs 9.03个月，P=0.036)。结论初治SCLC患者肿瘤组织中CD44的表达水平与PFS相关，CD44在SCLC中的临床意义值得进一步深入研究。

Immunohistochemical evaluation of suspected oral malignant melanoma in cats.

Oral malignant melanoma (OMM) is considered the third most common oral malignant neoplasm in cats, but its variable morphology and frequent lack of melanin pigment make it a diagnostic challenge. Twenty-two cases of cats with malignant oral neoplasms that were diagnosed as OMM or listed OMM as a suspected differential diagnosis on the biopsy report were examined using an immunohistochemistry (IHC) panel for S100, melan-A, PNL2, laminin, CD34, and pan-cytokeratin. Although OMM was suspected (n = 14) or previously diagnosed (n = 8), only 2 cases were immunohistochemically confirmed as OMM. Seven cases were classified as soft tissue sarcoma based on positive expression of CD34 or laminin, and one was classified as carcinoma based on positive expression of pan-cytokeratin. The majority of cases (n = 12) were categorized as unclassified malignant neoplasms because they did not express melan-A, PNL2, laminin, CD34, or pan-cytokeratin; however, a proportion of these did express S100 (n = 7). Long-term prognosis of all 22 cats was poor, with a median survival time of 87 days (range = 2-249 days). Cases with longer survival times (>100 days) were treated with surgery, radiation therapy, or a combination. For feline oral malignant neoplasms thought to be OMM, routine use of IHC is required for an accurate diagnosis.

CD34 and Bcl-2 as predictors for the efficacy of neoadjuvant chemotherapy in cervical cancer

BackgroundSuccessful neoadjuvant chemotherapy (NACT) could improve the surgical resection rate and radical curability of patients with cervical cancer, but only a subset of patients benefits. Therefore, identifying predictive biomarkers are urgently needed. The aim of this study was to evaluate the predictive value of CD34 and Bcl-2 in the NACT effectiveness of cervical cancer.MethodsSixty-seven patients with locally advanced cervical cancer (FIGO stages IB3, IIA2 or IIB) were classified into two groups based on effective (n = 48) and ineffective (n = 19) response to NACT. Immunohistochemistry was employed to identify CD34 and Bcl-2 expression before and after NACT. We analyzed the associations between the pre-NACT expression of these two biomarkers and the response of NACT. The expression of these two biomarkers before and after NACT was also assessed and compared.ResultsMore patients were CD34 positive expression before NACT in effective group compared to ineffective group (p = 0.005). However, no statistically significant difference in Bcl-2 expression before NACT were found between two groups (p = 0.084). In NACT effective group, the expression of both CD34 and Bcl-2 after NACT are down-regulated (p < 0.001 and p < 0.001, respectively), while there are no statistical differences between the pre- and post-NACT expression of CD34 and Bcl-2 in NACT ineffective group (p = 0.453 and p = 0.317, respectively).ConclusionThe positive CD34 expression before NACT may serve as a predictive biomarker for NACT of cervical cancer, but the pre-NACT expression of Bcl-2 is not an independent predictor. The down-regulated expression of these two indicators after NACT may indicate effective NACT.

ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER?

ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim:Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

Effect of porcine corneal stromal extract on keratocytes from SMILE-derived lenticules.

Propagating large amounts of human corneal stromal cells (hCSCs) in vitro while maintaining the physiological quality of their phenotypes is necessary for their application in cell therapy. Here, a novel medium to propagate hCSCs obtained from small incision lenticule extraction (SMILE)‐derived lenticules was investigated and the feasibility of intrastromal injection of these hCSCs was assessed. Primary hCSCs were cultured in porcine corneal stroma extract (pCSE) with RIFA medium including ROCK inhibitor Y27632, insulin‐transferrin‐selenium, fibroblast growth factor 2, L‐ascorbate 2‐phosphate and 0.5% FBS (RIFA medium + pCSE). Protein profiling of the pCSE was identified using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC‐MS/MS). After subculturing in RIFA medium + pCSE or 10% FBS normal medium (NM), hCSCs at P4 were transplanted into mouse corneal stroma. Compared with NM, ALDH3A1, keratocan and lumican were significantly more expressed in the RIFA medium + pCSE. ALDH3A1 was also more expressed in the RIFA medium + pCSE than in the RIFA medium. Fibronectin and α‐SMA were less expressed in the RIFA medium + pCSE than in the NM. Using Metascape analysis, the pCSE with its anti‐fibrosis, pro‐proliferation and anti‐apoptosis activities, was beneficial for hCSC cultivation. The intrastromally implanted hCSCs in the RIFA medium + pCSE had positive CD34 expression but negative CD45 expression 35 days after injection. We provide a valuable new medium that is advantageous for the proliferation of hCSCs with the properties of physiological keratocytes. Intrastromal injection of hCSCs in RIFA medium + pCSE has the potential for clinical cell therapy.

Primary hepatic malignant vascular tumors: a follow-up study of imaging characteristics and clinicopathological features

BackgroundOwing to its low incidence, there is insufficient clinical awareness and diagnostic experience with primary hepatic malignant vascular tumors (PHMVTs). The aim of our study was to investigate the imaging and clinicopathological features of patients with PHMVTs and analyze the clinicopathological correlations.MethodsWe retrospectively analyzed 42 patients who had pathologically confirmed PHMVT during the period from June 2012 to December 2019 and enrolled them in our study. The computed tomography (CT) and magnetic resonance (MR) images and pathological findings of each patient were recorded.ResultsThere were more female (29/42) than male patients. The imaging features of primary hepatic angiosarcoma (PHA) (n = 11) included ill-defined margins (11/11, 100%), necrosis (5/11, 45%), calcification (3/11, 27%) and “slow in-slow out” centripetal enhancement (7/11, 64%). Patients with epithelioid hemangioendothelioma (EHE) (n = 15) presented with ill-defined margins (15/15, 100%), necrosis (6/15, 40%), calcification (2/15, 13%), “fast in-slow out” centripetal enhancement (10/15, 67%), halo sign (15/15, 100%), pseudocapsule sign (4/15, 27%), lollipop sign (2/15, 13%) and capsule retraction sign (2/15, 13%). Patients with malignant hemangiopericytoma (MHP) (n = 3) showed ill-defined margins (3/3, 100%), necrosis (3/3, 100%) and “fast in-slow out” progressive enhancement (3/3, 100%). Infantile hemangioendotheliomas (IHEs) (n = 13) were defined by ill-defined margins (7/13, 54%), necrosis (8/13, 62%), calcification (5/13, 38%) and “fast in-slow out” centripetal enhancement (13/13, 100%). Immunohistochemistry showed strong positive expression of CD31, CD34, ERG, FaVIII and FLI-1. Patients with IHE (96 months) and EHE (88 months) had the longest survival times, followed by those with MHP (23 months), while patients with PHA (15 months) had the shortest survival time.ConclusionOn CT and MR images, most PHMVTs were ill-defined, heterogeneous, hypervascular masses with centripetal progressive enhancement and possibly calcification, especially in female patients. The prognosis of patients with PHMVT was associated with the pathological type of the tumor.