Expression Of CD44s Research Articles

CD44 expression during tumor progression of follicular lymphoma

Follicular lymphoma often progresses to diffuse type lymphoma. To elucidate the mechanisms of the diffuse evolution of follicular lymphoma, we investigated the expression pattern of CD44 in 28 cases of follicular lymphomas (FLs) using an immunohistochemical method and semi-quantitative PCR-Southern blot analysis. The FLs were divided into four groups: i) intrafollicular (IF); ii) infiltrative (INF); iii) partially follicular (PF); and iv) minimally follicular (MF), according to the histological classification by Lukes and Collins. Immunohistochemical analysis of CD44 using antibodies against CD44 common (CD44C) epitopes showed that CD44 was expressed in the diffuse area in the INF (0/8 cases), PF (12/12 cases), and MF (2/2 cases) lymphomas, whereas CD44 was not expressed in the lymphoma cells within the area of follicular growth of IF (0/6 cases) and INF (0/8 cases). Semi-quantitative PCR-Southern blot analysis showed that CD19-selected B cells from the FLs were expressed as a product of 482 base pairs (bp) corresponding to a CD44 standard form (CD44s) (5/5 cases). Additionally, the lymphoma cells from the PF were expressed as products of 600 and 1100 bp and the cells from MF were expressed as products of 600, 900, and 1100 bp with the CD44 exon 10 or 11 probes. The results indicated that the expression of CD44s and CD44 variants containing exon 10 and 11 were up-regulated according to the diffuse evolution of the follicular lymphoma.

CD44 variant isoforms in head and neck squamous cell carcinoma progression

The CD44 family of receptors includes multiple variant isoforms, several of which have been linked to malignant properties including migration, invasion, and metastasis. The objective of this study was to investigate the role of the CD44 v3, v6, and v10 variant isoforms in head and neck squamous cell carcinoma (HNSCC) tumor progression behaviors. Laboratory study involving cell cultures and clinical tissue specimens. Analysis of the expression of standard CD44s and the CD44 variant isoforms v3, v6, and v10 was carried out in the HNSCC cell line, HSC-3. The role of CD44 isoforms in migration, proliferation, and cisplatin resistance was determined. Immunohistochemical analysis was performed on clinical tissue specimens obtained from a series of 82 HNSCC patients. The expression of standard CD44s and the CD44 v3, v6, and v10 variants in primary tumor specimens (n = 82) and metastatic cervical lymph nodes (n = 24) were analyzed with respect to various clinicopathologic variables. HSC-3 cells express at least four CD44 isoforms, and these CD44 isoforms mediate migration, proliferation, and cisplatin sensitivity. Compared with primary tumors, a greater proportion of metastatic lymph nodes demonstrated strong expression of CD44 v3 (lymph node 14/24 vs. primary tumor 38/82), CD44 v6 (lymph node 18/24 vs. primary tumor 26/82), and CD44 v10 (lymph node 14/24 vs. primary tumor 16/82), while expression of standard CD44 was not significantly different in metastatic lymph nodes and primary tumors (lymph node 10/24 vs. primary tumor 60/82). Expression of CD44 variant isoforms were associated with advanced T stage (v3 and v6), regional (v3) and distant (v10) metastasis, perineural invasion (v6), and radiation failure (v10). CD44 v6 and CD44 v10 were also significantly associated with shorter disease-free survival. CD44 isoforms mediate migration, proliferation, and cisplatin sensitivity in HNSCC. Furthermore, expression of certain CD44 variants may be important molecular markers for HNSCC progression and should be investigated as potential therapeutic targets for therapy.

Expression of standard CD44 in human colorectal carcinoma: Association with prognosis

The aim of the present study was to evaluate the expression of standard CD44 (CD44s) in colorectal cancer (CRC), its relationship with clinicopathological characteristics, and its potential prognostic significance. CD44s levels were measured on immunohistochemistry in tumors and surrounding normal mucosa from 74 patients with primary colorectal carcinomas. The patients were followed for a median period of 37 months. Expression of CD44s in primary tumor and surrounding normal mucosa tissues was demonstrated in 100% (74/74) and 37.9% (28/74), respectively. The expression of CD44s in tumors was significantly associated with the depth of invasion (P = 0.034) and lymph node involvement (P = 0.031). A significant difference was observed between the overall survival and level of tumor CD44s expression, especially for stage IV carcinoma (P = 0.038). Multivariate analysis indicated that TNM stage (P = 0.020) and tumor CD44s expression (P = 0.008) were independent predictors of overall survival in adenocarcinomas. CD44s overexpression may be an independent unfavorable prognostic factor for overall survival in advanced CRC, especially stage IV disease. Further investigation, however, is necessary to assess the biological roles of CD44 in CRC, and validate their possible value as novel therapeutic targets.

The Effect and Significance of Cinobufagin on the Expression of CD44s in Ovarian Carcinoma 3AO Cells

Objegtive To investigate the effect and significance of cinobufagin on the expression of CD44s in ovarian carcinoma 3AO cells cultured in vitro.Methods Ovarian carcinoma 3AO cells were cultured in vitro;after the intervention of tinobufagin with different concentration,the expression of CD44s was measured by RT-PCR,and the cellular apoptosis was tested by flow cytometry.Results Ovarian carcinoma 3AO cells expressed CD44S mRNA of 1.3±0.1 and the cellular apoptofic rate was(2.31±0.98)%:0.25 mg/ml cinobufagin did not affect CD44s mRNA and cellular apoptofic rate(P ＞0.05):when 2.5 mg/ml cinobufagin was intervened,the expression of CD44s mRNA was 1.0±0.1 and the cellular apoptotic rate Was(28.69±4.16)%,showing significant difference comparing with the control group of ovarian carcinoma 3AO ceils(P＜0.05):the intervention of 25 mg/ml cinobufagin was similar to that of 0.25 mg/ml cinobuhgin(P＞0.05).3AO cells. Key words: Cinobufagin ; Ovarian carcinolna ; CD44s ; Invasive growth ;

Role of Osteopontin and CD44s Expression for Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation or Resection

Background Detection of new biomarkers for hepatocellular carcinoma (HCC) is needed to estimate prognosis after liver transplantation (OLT) or hepatic resection. Osteopontin (OPN) is a secreted, calcium-binding, phosphorylated, acidic glycoprotein that is overexpressed in various cancers. Cluster differentiation 44 standard isoform (CD44s) is one of the primary receptors of OPN; it may contribute to metastatic tumor spread. Materials and Methods Tumor tissue and surrounding hepatic parenchyma were obtained from 53 HCC patients who underwent liver resection. Their RNA was extracted from nitrogen-frozen tissues, and OPN mRNA levels were estimated by quantitative reverse transcription–polymerase chain reactions. Formalin-fixed, paraffin-embedded tissues were obtained from the same patients, and additionally from 60 OLT HCC patients to perform expression analysis for OPN and CD44s by standard avidin-biotin immunostaining methods. Results Expression of OPN and CD44s was significantly higher among HCC compared with adjacent nontumor tissue. The OPN mRNA expression and protein abundance correlated positively; OPN overexpression was associated with high tumor grade. A positive correlation existed between OPN and CD44s expression; both proteins were significantly overexpressed in HCC lesions with positive lymph nodes. No significant correlation existed between patient survival and OPN and CD44s expression. Conclusion Expression of both OPN and CD44s in HCC is associated with advanced tumor stage, thus possibly contributing prognostic information when evaluated together with classical clinicopathological parameters.

CD44s and CD44v6 Expression in Head and Neck Epithelia

BackgroundCD44 splice variants are long-known as being associated with cell transformation. Recently, the standard form of CD44 (CD44s) was shown to be part of the signature of cancer stem cells (CSCs) in colon, breast, and in head and neck squamous cell carcinomas (HNSCC). This is somewhat in contradiction to previous reports on the expression of CD44s in HNSCC. The aim of the present study was to clarify the actual pattern of CD44 expression in head and neck epithelia.MethodsExpression of CD44s and CD44v6 was analysed by immunohistochemistry with specific antibodies in primary head and neck tissues. Scoring of all specimens followed a two-parameters system, which implemented percentages of positive cells and staining intensities from − to +++ (score = %×intensity; resulting max. score 300). In addition, cell surface expression of CD44s and CD44v6 was assessed in lymphocytes and HNSCC.ResultsIn normal epithelia CD44s and CD44v6 were expressed in 60–95% and 50–80% of cells and yielded mean scores with a standard error of a mean (SEM) of 249.5±14.5 and 198±11.13, respectively. In oral leukoplakia and in moderately differentiated carcinomas CD44s and CD44v6 levels were slightly increased (278.9±7.16 and 242±11.7; 291.8±5.88 and 287.3±6.88). Carcinomas in situ displayed unchanged levels of both proteins whereas poorly differentiated carcinomas consistently expressed diminished CD44s and CD44v6 levels. Lymphocytes and HNSCC lines strongly expressed CD44s but not CD44v6.ConclusionCD44s and CD44v6 expression does not distinguish normal from benign or malignant epithelia of the head and neck. CD44s and CD44v6 were abundantly present in the great majority of cells in head and neck tissues, including carcinomas. Hence, the value of CD44s as a marker for the definition of a small subset of cells (i.e. less than 10%) representing head and neck cancer stem cells may need revision.

Expression of CD44s, CD44v6, and Hyaluronan Across the Spectrum of Normal-hyperplasia-carcinoma in Breast

The interaction between transmembrane receptors on epithelial tumor cells and the surrounding extracellular matrix molecules is important in tumor progression and metastasis. This interaction is best exemplified by the relationship of the receptor CD44 and the extracellular matrix component hyaluronan (HA). This study seeks to evaluate the expression and the correlation of CD44s, CD44v6, and HA in normal, hyperplastic, and malignant breast epithelium and stroma. Archival paraffin-embedded tissue from cases of normal breast tissue (n=10), intraductal hyperplasia without atypia (n=13), ductal carcinoma in situ (DCIS) (n=24), stage I infiltrating ductal carcinoma (n=28), stage II infiltrating ductal carcinoma (n=31), and their corresponding positive lymph nodes were retrieved from the surgical pathology files. Tissue sections were evaluated for the expression of CD44s, CD44v6, and HA in the epithelial and stromal cells by immunohistochemistry. Ductal epithelial cells and myoepithelial cells expressed CD44s in all cases of normal and benign breast tissue. The expression of CD44s in breast epithelium progressively decreased with increasing deviation from normal histology: 83% in DCIS, 46% in stage I ductal carcinoma and 26% in stage II ductal carcinoma. The reverse trend was observed for CD44v6 in ductal epithelium: 0% in normal breast, 15% in intraductal hyperplasia, 100% in DCIS, 82% in stage I infiltrating ductal carcinoma, 94% in stage II carcinoma, and 100% of metastatic carcinoma in the lymph nodes. HA was noted exclusively in the stroma but not in the epithelial cells. HA was faintly expressed in the intralobular stroma of normal breast tissue, confined to a narrow faint band adjacent to intraductal hyperplasia and localized to a broad well-defined band around DCIS. Stromal HA staining was more diffuse and intense in infiltrating carcinomas and was particularly pronounced surrounding the metastatic deposits in lymph nodes. This study demonstrates decreased expression of CD44s accompanied by increased expression of CD44v6 and increased stromal HA in breast cancer. These findings suggest that CD44s, CD44v6, and HA play complementary roles in the development and progression of breast cancer.

Prognostic Significance of CD44s Expression in Biliary Tract Cancers

CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers. Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed. Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37-86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211-.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630-3.393; P = .377) had no prognostic significance for survival. CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.

In Vivo Evidence for the Role of CD44s in Promoting Breast Cancer Metastasis to the Liver

The hyaluronan receptor CD44 plays an important role in facilitating invasion and metastasis of a variety of tumors, including breast carcinomas. CD44 functions as a bioactive signaling transmitter. Although a number of studies have implicated CD44 in breast tumor invasion, the evidence is still circumstantial. We have developed a tetracycline-regulated CD44s (standard form) system in the weakly metastatic breast cancer cell MCF7, which exhibits low endogenous expression of CD44 and generated a new cell line, MCF7F-B5. Induction of CD44s alone affected the growth characteristics of MCF7F-B5 cells by increasing their abilities to proliferate, migrate, and invade in vitro. In addition, we have identified and validated cortactin as a novel transcriptional target of hyaluronan/CD44s signaling in underpinning breast tumor invasion. To test these observations in vivo, we developed a doxycycline (DOX)-regulated CD44s breast cancer xenograft model. Induction of CD44s did not affect the growth rate or local invasion of the primary tumor. However, although no mice from the +DOX group developed metastasis, 8 of 11 mice from the -DOX group developed secondary tumors to the liver only. Interestingly, metastatic breast tumors expressed high levels of CD44. This study provides in vivo evidence for the role of the standard form of CD44 in promoting breast tumor invasion and metastasis to the liver.

Pseudomyxoma Peritonei: Clinical Pathological and Biological Prognostic Factors in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Surgical cytoreduction combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been recently advocated as the standard of care for pseudomyxoma peritonei (PMP). We reviewed our 10-year monoinstitutional case series to identify selection factors predicting postoperative outcome. One hundred and four patients with PMP were operated on with the aim of performing adequate cytoreduction (residual tumor nodules < or =2.5 mm) and closed-abdomen HIPEC with mytomicin-C and cisplatin. Previously, 26 patients had systemic chemotherapy. PMP was histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and intermediate/discordant group (ID). Immunohistochemical stains were performed for cytokeratin (CK)-7, CK-20, CDX-2, MUC-2, MUC-5AC, CD-44s. The significance of 22 potential clinical, pathological, and biological prognostic variables was assessed by multivariate analysis. Adequate cytoreduction was performed in 89 patients, suboptimal cytoreduction in six, palliative surgery in nine. Operative mortality was 1%. Seventy-eight patients were diagnosed with DPAM, 26 with PMCA, and none with ID. Median follow-up was 37 months (range, 1-110) for the overall series. Five-year overall survival (OS) and progression-free survival (PFS) were 78.3% and 31.1%, respectively. At multivariate analysis, adequate cytoreduction, no previous systemic chemotherapy, and DPAM correlated to better OS and PFS, elevated serum CA19.9 correlated only to better PFS. In most cases, CK20, CDX-2, and MUC-2 were diffusely positive, while CK-7, MUC-5AC, and CD44s were variably expressed. CK20 expression correlated to prognosis at univariate analysis. Favorable outcome after comprehensive treatment can be expected in patients with DPAM, not treated with preoperative systemic chemotherapy and amenable to adequate cytoreduction. MUC-2, CK-20, and CD44s expression may be related to PMP unique biologic behavior.

Expression of CD44s and CD44v6 in transitional cell carcinomas of the urinary bladder: comparison with tumour grade, proliferative activity and p53 immunoreactivity of tumour cells

Alterations of CD44 glycoproteins have been shown to play an important role in progression of various malignancies, including urothelial cancer. We investigated expression patterns of CD44s and CD44v6 in transitional cell carcinoma (TCC) of the urinary bladder in relation to tumour grade, proliferative activity, and immunoreactivity for p53. The selected markers were detected immunohistochemically in 122 samples of TCC. We found a close relationship between CD44s and CD44v6 expression and tumour grade. The extension of positive staining for CD44s and CD44v6 towards the luminal surface was a predominant feature of differentiated carcinomas (grades 1 and 2), suggesting deranged maturation of cancer cells related to their neoplastic transformation. Heterogeneous expression of CD44s and CD44v6 predominated in poorly differentiated tumours (G3-4). However, areas of squamous differentiation within the high-grade tumours displayed strong immunoreactivity for both CD44s and CD44v6. The proliferative activity and p53 overexpression increased with the dedifferentiation of the tumour. The results of this study are discussed in relation to the significance of CD44 expression in TCC and to the explanation for controversial results reported in previous studies on the relationship between CD44 expression and the biological behaviour of urothelial cells.

Prognostic significance of p21WAF1/CIP1, p16INK4a and CD44s in tongue cancer

The role of lost or reduced expression of p21, p16 and CD44s in the survival of tongue cancer patients was investigated. Tumours and adjacent non-tumour epithelia (ANTE) from 36 patients with tongue cancer were retrospectively studied by immunohistochemistry using monoclonal antibodies against p21, p16 and CD44s proteins. Expression of p21, p16 and CD44s and their relationship with clinical and pathological parameters were analyzed. Of 36 patients, 12 (33.33%) developed recurrence and 12 died of the disease (mean survival, 25.5 months). In four cases (11.1%), concomitant low expression (<50% of tumour cells) of p21, p16 and CD44s was detected but had no effect on survival or recurrence in the univariate analysis. In the multivariate analysis, low expression of CD44s was the sole prognostic factor related to survival (p=0.01, hazards ratio: 0.749). There was no expression of p21, p16 or CD44s in ANTE from 3 out of 24 cases studied, and this finding was related to recurrence in the univariate analysis. In the multivariate analysis, low expression of CD44s in ANTE was again the sole factor related to recurrence (p=0.002, hazards ratio: 0.028). In conclusion, low expression of CD44s is related to tumour cell invasiveness and may be of clinical relevance as a prognostic factor.

CD44 standard isoform expression is associated with diffuse large B cell lymphoma of non-germinal center B cell-like types

18531 Background: Diffuse large B cell lymphoma (DLBCL) can be subdivided into germinal center B cell-like (GCB) and non- germinal center B cell-like (Non-GC) types by immunohistochemical profiling. Previous studies showed better survival rate for the GCB groups. CD44 is necessary for tumor spread and metastasis and its expression is generally associated with unfavorable prognosis. We analyzed the expression and prognostic significance of standard isoform CD44s and its variant isoform CD44v6 in DLBCL types. Methods: Tissue microarray blocks were created from 52 nodal DLBCL with control tissue. Immunohistochemical staining for CD10, Bcl-6, MUM-1, CD44s, and CD44v6 were performed. The median follow-up period was 44 months. Results: Nodal DLBCLs were subclassified into GCB [CD10+ or CD10-/Bcl6+/MUM1+, n=17 (33%)] and non-GC subgroups [CD10-/Bcl6- or CD10-/Bcl6+/MUM1+, n=35 (67%)]. CD44s expression appeared more on non-GC cases of DLBCL (p=0.04). CD44s and CD44v6 did not result in any difference according to tumor stage, IPI scores, LDH levels. Upon survival analysis, CD44s and CD44v6 expression did not show any statistical correlation. Conclusions: CD44s expression may play a role during lymphomatogenesis of non-GC type DLBCL. No significant financial relationships to disclose.

Metastatic renal clear cell carcinoma in the parotid gland: A study of immunohistochemical profile and cell adhesion molecules (CAMs) expression in two cases

Metastasis of renal cell carcinoma (RCC) may involve any organ, including the parotid salivary gland. While the definition of salivary gland neoplasms with clear cell transformation can be concluded by the synchronous presence of areas showing typical morphology, sometimes the definition of a metastatic RCC in the parotid is difficult and the application of immunohistochemistry may support the clinical and radiographic observations in the final diagnosis. The aim of this paper was to describe the heterogeneous immunohistochemical features and, furthermore, to characterize the pattern of expression of cell adhesion molecules (CAMs) E-cadherin, beta4-integrin, desmoglein-2, ICAM-1 and CD44s (HCAM) in two cases of metastatic parotid RCC.

Immunohistochemical Staining of Papillary Breast Lesions

The separation of ductal papilloma from intraductal papillary carcinoma of the breast on hematoxylin and eosin stained sections often presents diagnostic difficulty. Immunohistochemical staining is often employed in diagnosis, historically with smooth muscle actin (SMA). In this study, the staining characteristics of a panel of myoepithelial markers (calponin, p63, P-cadherin), were compared with SMA, and the epithelial expression of CD44s was assessed in 99 papillary lesions. SMA, calponin, and p63 demonstrated myoepithelial cells in 61%, 63%, and 65% of papillary lesions, respectively. However, specificity was quite variable. Calponin-stained stromal myofibroblasts (35% of cases), vessel pericytes (92%), and endothelial cells (69%), though each to a lesser degree than SMA. Calponin also showed cross reactivity with epithelium in 18% of cases. p63 was almost completely restricted to myoepithelial cell nuclei, and did not stain vascular smooth muscle or myofibroblasts. However, p63 stained the epithelial component in one papillary carcinoma, a basal layer of cells in 1 biphasic invasive carcinoma, and the cytoplasm in 1 case. P-cadherin stained both epithelial and myoepithelial cells. The epithelial expression of CD44s and did not distinguish papillomas from papillary carcinomas. Thus, P-cadherin and CD44s are not useful in the characterization of papillary lesions. Given increased specificity as compared with SMA, the combination of p63 and calponin is recommended for analysis of breast papillary lesions.

Comparison of CD44 expression in primary tumours and metastases of colorectal cancer

A better understanding on the development of a metastatic phenotype in colorectal cancer (CRC) is essential to help identify patients at high risk for metastasis. Therefore, we have studied the role of the CD44 family of trans-membrane glycoprotein in the process of CRC metastasis, by examining the expression of CD44s and CD44v6 in primary tumours and their metastatic lesions in 46 patients using immunohistochemistry. The expression of both CD44s and CD44v6 was significantly higher (moderate/strong) in primary tumours as compared to their metastases (p=0.008, p=0.0001, respectively). CD44s expression in metastases increased with the degree of the histological grade (p=0.009) and invasiveness of the primary tumour (p=0.002). Disease-free survival (DFS) was shorter in patients who had metastases with a strong/moderate expression of CD44s as compared to those with negative/weak expression (8.3 months vs 16.9 months p=0.221, respectively). Our finding that CD44s expression in metastatic lesions may reflect the aggressiveness of the primary tumour from which it has originated implicates an important link between the two lesions. CD44 expression may also provide valuable biological information as suggested by the observation that up-regulated CD44s expression in metastases is associated with a shorter DFS.

Prognostic significance of CD44s expression in bile duct carcinomas

14071 Background: CD44 is a surface glycoprotein and has a key role for surface hyaluronan receptor, which is associated with adhesion and metastasis in many solid tumors. There are CD44 standard isoform (CD44s) and ten variant isoforms (CD44v1–10). CD44s and CD44 variant 6 (CD44v6) were evaluated to clarify the applicable prognostic factor in patients with bile duct carcinomas. Methods: A retrospective study was performed in bile duct carcinomas. Immunohistochemical stain was done with primary antibodies for CD44 (Novocastra, Newcastle upon Tyne, UK) and CD44v6 (Novocastra) using automated machine (Vision Biosystems, Mount Waverley, VIC, Australia) and bond polymer detection system with counterstain (Vision Biosystems) in paraffin embedded tissues. The extent of staining categorized as 0% (none), &lt;10% (weak), 10%-50% (moderate), and &gt;50% (strong). Clinical characteristics including age, sex, stage, grade and overall survival were reviewed. Results: Ninety six patients (M:F=35:61) were evaluated and the median age of these patients was 64 years old (37∼86). The rate of overexpression (&gt;10%) of CD44s was 50% and the rate of CD44v6 expression was 16.9%. With median 34.2 months of follow up, the overall survival of total 96 patients was 12.2 months. The Cox proportional hazards test identified CD44s overexpression. (HR:2.379, 95% CI:1.195–4.736, p=0.014) and the stage as prognostic factors. But the expression of CD44v6 (weak vs. moderate to strong, HR:3.983, 95%CI:0.295–1.588, p=0.377) showed no prognostic significance on overall survival. Conclusion: CD44s overexpression can be a poor prognostic marker in bile duct carcinomas. And there is a potential to apply postoperative investigational or aggressive therapy in this poor prognostic group. No significant financial relationships to disclose.

Expression of CD44 in rat hepatic progenitor cells

Small hepatocytes (SHs) are hepatic progenitor cells, but the phenotypical difference between SHs and mature hepatocytes (MHs) has never been demonstrated. The profile of gene expression was examined to clarify the difference between SHs and MHs by using a DNA microarray. Genes that were specifically expressed in SHs were identified and RT-PCR analysis of them was performed. Immunocytochemistry for CD44 standard form (CD44s) and variant form 6 (CD44v6) was performed using cultured SHs and the d-galactosamine (GalN)-injured rat liver. From the GalN-treated liver, CD44s+ cells were obtained by sorting and RT-PCR analysis was performed. Analysis using the DNA microarray and RT-PCR of them revealed restricted expression of CD44s and CD44v6 in SHs. In culture, CD44s appeared at day 3 and increased with the proliferation of SHs. CD44v6 expression was delayed compared to that of CD44s. With GalN-administration, CD44+ hepatocytes appeared around periportal areas at days 3 and 4 and then decreased. Sorted CD44s+ cells could form colonies and possessed hepatic markers. CD44 is a specific marker of SHs. The expression of CD44 mRNA and protein is restricted to SHs, and is up-regulated at the time when SHs start to proliferate both in vitro and in vivo.

Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms

To clarify possible roles of adhesion molecules including E-cadherin, beta- and gamma-catenin, CD44s, CD44v6, CD56, and CD99 in ovarian serous neoplasms, an immunohistochemical study was undertaken for 23 benign, 40 borderline, and 95 malignant ovarian serous neoplasms using tissue microarray (TMA). Significantly reduced expression of E-cadherin, and overexpression of CD44s, CD56, and CD99 were more frequently observed in adenocarcinomas than in benign and borderline tumors. Expression of CD44v6 and nuclear beta- and gamma-catenin were detected only in borderline tumors and adenocarcinomas. Reduced expression of E-cadherin was also correlated with high tumor grade (P=0.03), presence of peritoneal seeding (P=0.03), and low overall survival rate (P=0.02). Overexpression of CD44s was significantly associated with high tumor grade (P=0.04), advanced stage (P=0.03), and low overall survival rate (P=0.02). CD56 was increasingly expressed in the case of advanced stage (P=0.005) and peritoneal seeding (P=0.001). Nuclear staining for gamma-catenin was correlated with tumor progression (P=0.004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.02). Only CD44s expression and stage were correlated with overall survival in multivariate study. These results suggest that although E-cadherin, CD44s, CD56, and nuclear gamma-catenin immuno-expression seem to be useful prognostic markers for serous neoplasm of the ovary, CD44s expression and FIGO stage are independent prognostic factors.

Activation of CD44 facilitates DNA repair in T-cell lymphoma but has differential effects on apoptosis induced by chemotherapeutic agents and ionizing radiation

Expression of CD44s (standard form) in malignant lymphoma is a poor indicator of survival. To investigate whether activation of CD44s can protect from cell death, this study compared the extent of apoptosis induced by chemotherapeutic agents and ionizing radiation (IR) on T-lymphoma cell lines in the presence or absence of adherent hyaluronan and monoclonal antibodies (MoAbs). Growth in the presence of adherent ligands enhanced apoptosis induced by dexamethasone (Dex), but protected cells from epirubicin-induced apoptosis. In IR-induced apoptosis, mouse lymphoma cells had resistance against apoptosis when treated with hyaluronan (HA), although acute cell death reached the same plateau regardless of treatment with adherent MoAbs in human lymphoma cell line. However, the post-irradiated repopulation of lymphoma cells was strikingly accelerated in those treated with CD44 adherent ligands. This repopulation process correlated with the remarkable upregulation of proliferating cell nuclear antigen (PCNA), which is a protein involved in DNA repair. Unscheduled DNA synthesis (UDS), a measure of DNA repair, was consistently enhanced in CD44s-stimulated cells after exposure to radiation. The results suggest that the poor prognostic indication of CD44 expression is more a consequence of enhanced DNA repair following genotoxic damage than of direct resistance to apoptosis.