Metastasising ability connotes one of the most important life-threatening properties of malignant neoplasms. Recent studies indicate that CD44 proteins, multifunctional cell adhesion molecules which contribute to "homing" of lymphocytes to lymph nodes as well as cell-cell and cell-matrix interactions, are potential markers of tumour progression. However, whether CD44 expression by human tumours contribute to increased metastatic risk remains controversial. In an attempt to clarify its role in breast cancer, we have investigated the correlation between CD44 expression by breast carcinoma and the presence of axillary lymph node metastases. CD44 expression was detected using a standard immunoperoxidase method on formalin-fixed, paraffin-embedded, primary infiltrating ductal breast carcinoma tissues taken from 60 female patients who underwent mastectomy with axillary node clearance. Tumours were graded according to the modified Bloom and Richardson criteria. 62% of patients had histologically-proven lymph node metastasis. 40% of primary cancers exhibited cytoplasmic membrane immunopositivity for CD44. 46% of primary tumours which have metastasied to axillary lymph nodes were CD44 positive whereas 30% of tumours which have not metastasised expressed CD44. CD44 positivity was expressed by 20% of grade 1, 31% grade 2 and 58% grade 3 tumours. Our results suggest that CD44 may have a role in the progression of breast cancer and emphasise the need to investigate its interaction with other mechanisms of cancer advancement.
Antigens, CD44 ; lymph nodes ; Neoplasm Metastasis ; Cells ; Malignant neoplasm of breast

BACKGROUND: The CD44 antigen is a widely distributed cell surface glycoprotein implicated in multiple physiological cellular functions including cell-cell adhesion, cell-substrate interaction and cell activation. In the skin, CD44 is normally expressed in epidermal keratinocytes and hair follicular, sebaceous and eccrine epithelial cells. The precise functions of CD44 are not yet clearly understood, though they appear to be involved in the mechanism of tumor invasion and metastasis. OBJECTIVE: The purpose of this study is to investigate the immunohistochemical expression of the CD44 molecule in the epidermal keratinocytic tumors with different biologic behaviors, such as squamous cell carcinoma(SCC),basal cell epithelioma(BCE), actinic keratosis(AK), bowen's disease, keratoacanthoma(KA), trichoepithelioma. METHODS: Routine paraffin sections of formalin-fixed 33 tissues (15 SCC, 23 BCE, 9 AK, 7 KA, 7 bowen's disease, 5 trichoepithelioma, 2 psoriasis, 2 lichen planus) were labeled with anti-CD44 monoclonal antibody using avidin-biotin- peroxidase complex. Normal skin served as the negative control. RESULTS: The results are as follows. 1. In SCC and KA, peripheral parts of the lesion were prominently stained. CD44v6 showed the strongest expression, followed by CD44s and CD44v4/5. The horn cyst and the keratin region of the horn pearl were not stained. The degree of staining was weaker in KA compared to SCC. 2. The degree of staining was weaker in BCC and TEE compared to SCC. The staining was more prominent at the center of the lesion than in the peripheral region. In TEE, stronger staining was found at the center or in the squamous epithelial region. 3. Among the seven cases of Bowen's disease, 4 cases were diffusely stained with all three CD44 types. In the other three cases, local staining with the standard type and diffuse staining with CD44v4/5 and CD44v6 were seen. 4. In AK, the early lesion showed decreased expression of CD44 in all three types. However, those with mature lesion and progression to SCC showed increased degree of staining in all three types of CD44. CONCLUSION: These results suggest that expression of CD44 in these keratinocytic tumors is not related to malignant transformation and metastasis, but instead may be related tumor differentiation.
Actins ; Animals ; Antigens, CD44 ; Bowen's Disease ; Epithelial Cells ; Hair ; Horns ; Keratinocytes ; Lichens ; Membrane Glycoproteins ; Neoplasm Metastasis ; Paraffin ; Peroxidase ; Psoriasis ; Skin

BACKGROUND: The CD44 antigen is a widely distributed cell surface glycoprotein implicated in multiple physiological cellular functions including cell-cell adhesion, cell-substrate interaction and cell activation. In the skin, CD44 is normally expressed in epidermal keratinocytes and hair follicular, sebaceous and eccrine epithelial cells. The precise functions of CD44 are not yet clearly understood, though they appear to be involved in the mechanism of tumor invasion and metastasis. OBJECTIVE: The purpose of this study is to investigate the immunohistochemical expression of the CD44 molecule in the epidermal keratinocytic tumors with different biologic behaviors, such as squamous cell carcinoma(SCC),basal cell epithelioma(BCE), actinic keratosis(AK), bowen's disease, keratoacanthoma(KA), trichoepithelioma. METHODS: Routine paraffin sections of formalin-fixed 33 tissues (15 SCC, 23 BCE, 9 AK, 7 KA, 7 bowen's disease, 5 trichoepithelioma, 2 psoriasis, 2 lichen planus) were labeled with anti-CD44 monoclonal antibody using avidin-biotin- peroxidase complex. Normal skin served as the negative control. RESULTS: The results are as follows. 1. In SCC and KA, peripheral parts of the lesion were prominently stained. CD44v6 showed the strongest expression, followed by CD44s and CD44v4/5. The horn cyst and the keratin region of the horn pearl were not stained. The degree of staining was weaker in KA compared to SCC. 2. The degree of staining was weaker in BCC and TEE compared to SCC. The staining was more prominent at the center of the lesion than in the peripheral region. In TEE, stronger staining was found at the center or in the squamous epithelial region. 3. Among the seven cases of Bowen's disease, 4 cases were diffusely stained with all three CD44 types. In the other three cases, local staining with the standard type and diffuse staining with CD44v4/5 and CD44v6 were seen. 4. In AK, the early lesion showed decreased expression of CD44 in all three types. However, those with mature lesion and progression to SCC showed increased degree of staining in all three types of CD44. CONCLUSION: These results suggest that expression of CD44 in these keratinocytic tumors is not related to malignant transformation and metastasis, but instead may be related tumor differentiation.
Actins ; Animals ; Antigens, CD44 ; Bowen's Disease ; Epithelial Cells ; Hair ; Horns ; Keratinocytes ; Lichens ; Membrane Glycoproteins ; Neoplasm Metastasis ; Paraffin ; Peroxidase ; Psoriasis ; Skin

BACKGROUND/AIMS: Cluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative prognostic factor depending on tumor type and is still an ambiguous prognostic indicator in other cancers, especially hepatocellular carcinoma (HCC). We investigated the relationship between CD44s expression and survival in HCC patients. METHODS: A total of 260 HCC samples were collected to generate a tissue microarray. Staining of the arrays with a primary mouse CD44s monoclonal antibody was followed by evaluation of the relationship between CD44s expression and tumor differentiation. The effect of CD44s expression on patient survival was analyzed. RESULTS: CD44s protein expression correlated with histological grade (most and worst Edmondson grade) of the HCC (p=0.029 and p=0.039, respectively) and adversely affected the disease free survival period based on univariate and multivariate analyses (p=0.038 and p=0.077, respectively). CONCLUSIONS: High CD44s protein expression correlates with shorter disease free survival and poorly differentiated HCC. CD44s-targeted therapy may be efficacious for HCC treatment in the future.
Animals ; Antigens, CD44 ; Carcinoma, Hepatocellular ; Disease-Free Survival ; Glycoproteins ; Humans ; Mice ; Multivariate Analysis ; Neoplasm Metastasis ; Protein Array Analysis ; Recurrence

BACKGROUND: Epithelial tumor cells with a CD44(+)/CD24(-/low) immunoprofile may have the ability to cause breast cancer. We studied these cells and their clinicopathological significance. METHODS: The clinicopathologic findings of 100 invasive ductal carcinoma (IDC) cases and 45 ductal carcinoma in situ (DCIS) cases were reviewed. CD44(+)/CD24(-/low) tumor cells were identified by immunohistochemistry, and their clinicopathological implications in IDC and DCIS were analyzed. RESULTS: IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells was significantly associated with larger mass, higher grade, estrogen receptor (ER) negativity, and tumor cells with a higher frequency of metastasis. The proportion of CD44(+)/CD24(-/low) tumor cells in IDC, and its DCIS components was not significantly different, whereas the proportion of CD44(+)/CD24(-/low) tumor cells was higher in DCIS than in the DCIS component of IDC (p < 0.001). CONCLUSIONS: IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells might correlate with aggressive features, such as ER and higher grades. Moreover, the proportion of CD44(+)/CD24(-/low) tumor cells in the DCIS components of IDC and DCIS might harbor different biology, which may lead to differences in cancer progression and early carcinogenesis.
Antigens, CD24 ; Antigens, CD44 ; Biology ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Estrogens ; Immunohistochemistry ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Prevalence

Some biological characteristics of human bone marrow mesenchymal stem cells (MSCs) cultured in vitro were observed. hMSCs were isolated from bone marrow and purified by density gradient centrifugation method, and then cultured in vitro. The proliferation and growth characteristics of hMSCs were observed in primary and passage culture. MSCs of passage 3 were examined for the purify by positive rate of CD29 and CD44 through flow cytometry. Human bone marrow MSCs showed active proliferation capacity in vitro. The purify of MSCs separated by our method was higher than 90%. It was concluded that hMSCs have been successfully cultured and expanded effectively. It provided a foundation for further investigation and application of MSCs.
Antigens, CD29/analysis ; Antigens, CD44/analysis ; Bone Marrow Cells/*cytology ; Cell Proliferation ; Cell Separation ; Cells, Cultured ; Flow Cytometry ; Mesenchymal Stem Cells/*cytology

BACKGROUND: Papillary carcinoma is one of the most common malignant thyroid tumors and an important prognostic factor is the lymph node status. CD44 is a cell adhesion molecule and is associated with metastasis. The purpose of this study was to discover whether CD44 is valuable in the diagnosis of the papillary carcinoma, and whether Ki-67 and p53 are correlated with CD44 in the papillary carcinoma. METHODS: We studied CD44, Ki-67 and p53 expressions in 34 cases of formalin-fixed paraffin embedded papillary thyroid carcinomas, and 20 cases of the follicular neoplasm using mouse anti-CD44 (H-CAM), Ki-67 and p53 monoclonal antibodies. RESULTS: Most of the papillary carcinomas expressed diffuse and intense membrane staining of CD44 (32/34 cases, 94.1%). Focal scattered immunoreactivity was observed in the follicular neoplasm (8/20 cases, 40.0%). The staining patterns of CD44 were similar in both follicular adenoma and carcinoma. Both groups with or without lymph node metastasis showed similar expression patterns for CD44. There were no differences in Ki-67 and p53 staining between papillary carcinomas and follicular neoplasms. CONCLUSIONS: The result shows that papillary carcinomas preferentially display the CD44 antigen, and it is a useful diagnostic tool in the equivocal cases. There is no correlation among CD44, Ki-67 and p53 expressions in the papillary carcinoma.
Adenoma ; Animals ; Antibodies, Monoclonal ; Antigens, CD44 ; Carcinoma, Papillary* ; Cell Adhesion ; Diagnosis ; Fibrinogen ; Lymph Nodes ; Membranes ; Mice ; Neoplasm Metastasis ; Paraffin ; Thyroid Gland* ; Thyroid Neoplasms

BACKGROUND: CD44 protein is known as a homing cellular adhesion molecule that is linked to diverse cellular functions such as adhesion, migration and invasion, which are all important in cancer progression and metastasis. The expression of CD44 standard and variant isoforms (CD44 standard isoform [CD44s] and CD44 splice variants containing exon v6 [CD44v6], respectively) is associated with an unfavorable clinical outcome in various neoplasms. METHODS: Forty patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) through biopsy at Hanyang University Hospital between 1996 and 2003 were included in this study. CD44 proteins expression was analyzed by immunohistochemical staining on a tissue microarray and the correlation of CD44 with the types of DLBCL and clinical parameters, including the factors defined by the International Prognostic Index, was evaluated. RESULTS: A high CD44s and intermediate to strong CD44v6 expression, including cytoplasmic membranous staining patterns, was present in 35% (14/40) and 25% (10/40) of DLBCL patients, respectively. High CD44s expression was correlated significantly with non-germinal center B-cell-like types (non-GCB, p=0.004) and patients with old age (p=0.041). CONCLUSIONS: High CD44s expression may be significantly associated with the non-GCB type compared to the GCB type and may be essential to the prediction of disease outcome in tumor stage III in DLBCL patients.
Antigens, CD44 ; B-Lymphocytes ; Biopsy ; Cytoplasm ; Exons ; Humans ; Lymphoma, B-Cell ; Lymphoma, Large B-Cell, Diffuse ; Neoplasm Metastasis ; Protein Isoforms ; Proteins

CD44 is a cell adhesion molecule with numerous isoforms created by mRNA alternative splicing. Expression of CD44 variants has been suggested to play a potential role in tumor progression and metastasis. We designed primers CD44V, CD44V6/7, CD44R1 and CD44V6-10 to analyze and compare the roles of each CD44 variants. Expressions of CD44 variants were investigated in normal colonic mucosa, the lymph nodes which was histopathologically free of cancer cell, and cancer tissues of 44 human colorectal cancer patients by RT-PCR method. The expression of CD44V was observed in 28 out of 39 (71.8%) tumors and 7 out of 11 (63.6%) N1 normal regional lymph nodes, and CD44V6/7 was observed in 28 out of 39 (71.8%) tumors and 9 out of 11 (81.8%) N1 normal regional lymph nodes. The expressions of CD44V and CD44V6/7 were most frequently observed compared with any other CD44 variants. In normal colonic mucosa, the expression of CD44 variants are low but in cancer tissue and its regional lymph node, the expression of CD44V and CD44V6/7 were significantly higher and more frequent than any other CD44 variants (p<0.05). These results suggest that CD44V and CD44V6/7 can be a molecular marker for colorectal cancer and its micrometastasis to the regional normal lymph node.
Alternative Splicing ; Antigens, CD44/genetics* ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/immunology* ; Gene Expression ; Human ; Lymph Nodes/pathology ; Lymph Nodes/immunology* ; Protein Isoforms/genetics

Background : CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.
Antibodies ; Antigens, CD44 ; Carcinogenesis ; Carcinoma, Renal Cell* ; Cell Movement ; Disease-Free Survival ; Exons ; Glycoproteins ; Humans ; Immunohistochemistry ; Kidney ; Lymph Nodes ; Microvessels ; Multivariate Analysis ; Neoplasm Metastasis ; Protein Isoforms*