Journal of Pathology and Translational Medicine

Original Articles

CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas.: Kyueng Whan Min, Young Ha Oh, Chan Kum Park, So Dug Lim, Wan Seop Kim; Korean J Pathol. 2011;45(6):589-595.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.589

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Abstract PDF: 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.

The Expression of CD44H and CD44v6 in Gastric Adenocarcinoma.: Myoung Jin Ju, Hae Kyung Lee, Kwang Min Lee, Dong Kyu Chung, Choo Hong Park; Korean J Pathol. 1997;31(4):326-331.

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Abstract PDF: CD44, also known as the Hermes antigen, H-CAM, pgp-1 antigen, and extracellular matrix receptor ECM-III, is a widely distributed integral membrane protein that exists in a variety of forms with different molecular sizes ranging from 85kd to 160kd. A number of evidence implicates CD44 as a cell adhesion molecule with a possible role in tumor progression. To evaluate the possible roles of CD44 in the metastatic process of gastric carcinoma to the regional lymph nodes, we applicated immunohistochemical stains with the CD44H and CD44v6 primary antibodies onto the 2 groups of gastric adenocarcinomas. Each group was comprised of 22 primary tumors extending to the subserosa, and one group showed nodal metastasis, while the other group did not. Seventeen primary tumors (77%) out of the 22 cases with the nodal metastasis demonstrated positivity to the CD44v6, while only 9 primary tumors (41%) out of the 22 cases without nodal metastasis did. However CD44H immunoreactivity was demonstrated in tumor cells of all cases (100%) of both groups as well as in the normal cell components. These results suggest that CD44H form is not related to the metastasis to the regional lymph nodes of gastric carcinoma. However, the expression of CD44v6 seems to play a certain role in the metastatic process of the gastric carcinoma.

Expression of Cell Adhesion Molecules -CD44H and CD44v6- in Colorectal Carcinoma.: Dae Cheol Kim, Seo Hee Rha, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1998;32(9):655-662.

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Abstract: During tumor progression, a subset of cells acquires metastatic properties, presumably through a series of genetic alterations. As the result, cells detach from the primary tumor, penetrate the basement membrane and invade the adjacent structures including lymph and blood vessels. Loss of adhesive functions and gain of new adhesive functions are thought to play a crucial role in this metastatic cascade. Since tumor metastasis is the principle cause of death for cancer patients including colon cancer, there is a consensus that a search for tools that allow effective assessment of the metastatic potential of tumors is a prime goal for cancer research. An immunohistochemical study of cell adhesion molecules, CD44H and its variant CD44v6, was done to evaluate their relationship with known prognostic factors related to the progression and metastasis of colorectal carcinoma in 94 cases of colorectal carcinoma tissues. The results were as follows. The CD44H expression was detected in 90 (95.7%) and CD44v6 in 53 (56.4%) out of 94 cases of colorectal carcinoma, and the CD44H was overexpressed in tumor tissue more than in normal mucosa in 62% of the cases. The expression rates of both protein were not significantly correlated with age and sex of the patients, invasion depth, lymph node metastasis, tumor differentiation, and tumor site. The coexpression of CD44H and CD44v6 in tumor was significant (p<0.05). The above results suggest that overexpression of CD44H and loss of function to control the alternative splicing of CD44 mRNA resulting in CD44v6 expression and alteration of adhesive function are closely associated with tumorigenesis of the colorectum.

Comparison of the Expression of Variants of CD44 between Node-positive and Node-negative Breast Carcinomas.: In Ae Park, Ho Chang Lee, Soo Youn Cho; Korean J Pathol. 2005;39(3):172-180.

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Abstract PDF: BACKGROUND
The purpose of this study is to determine the value of CD44 and its splice variants as markers for the metastatic potential of infiltrating ductal carcinomas of the breast.
METHODS
Tissue samples of infiltrating ductal carcinoma of the breast were examined for the expression of standard CD44 (CD44H) and s CD44 isoforms, v3, v4-5 and v6 in 41 node-positive and 31 node-negative cases. The immunohistochemistry results were correlated with other clinicopathologic parameters, and these results were correlated with accompanying high grade and non-high grade DCIS areas of the tumors in both node-positive and node-negative cases.
RESULTS
The expression of CD44 in the invasive tumor areas and in the metastatic foci of the lymph nodes showed a statistically significant correlation. The expression of CD44H in the invasive tumor areas and the DCIS area showed a statistically significant correlation in the lymph node (-) group. There was statistical significance between the CD44 H and CD44v3 expressions and the histologic grade of the invasive tumor in the cases with positive lymph nodes. There was no statistical significance between CD44 expression and lymph node metastasis, tumor size and type of tumor margin.
CONCLUSIONS
We conclude that changes in the CD44 expression in breast cancer occur early in breast carcinogenesis, and this is involved in tumor differentiation, but we could not establish any correlation between the expression of the CD44 variant isoforms and the metastasis of breast cancer.

Studies of CD44s and CD44v6 Expressions and Correlation with Clinicopathologic Parameters in Gastric Carcinoma.: Zhu Hu Li, Zhen Hua Lim, Ho Jong Jeon; Korean J Pathol. 2003;37(5):320-324.

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Abstract PDF: BACKGROUND
The aim of this study is to elucidate the relationship between the CD44s and CD44v6 expression level and the biological characteristics of a gastric carcinoma.
METHODS
CD44s and CD44v6 expression was investigated in 56 gastric carcinomas, 18 dysplasias, and 22 normal mucosae by immunohischemical staining.
RESULTS
The CD44s and CD44v6 expression rates in gastric carcinomas, dysplasia, and normal mucosae were 80.3% and 83.9%, 72.2% and 77.8%, and 13.6% and 4.5%, respectively. Statistical analysis showed significant difference after comparing a gastric carcinomas and dysplasia to the normal mucosae (p<0.001). The CD44s and CD44v6 expression rates in the cases with invasion to the muscle proper and serosa were 60.7% and 57.1%, and 82.4% and 88.2%, respectively. Both showed a significant statistical difference compared to the expression rates in the cases with invasion to the mucosae and submucosae. The CD44s and CD44v6 expression rates in gastric carcinomas with a lymph node metastasis showed a statistically significant difference compared to those without a lymph node metastasis (p<0.001 and p<0.01, respectively). CD44s and CD44v6 were also expressed in the normal basal cells around gastric carcinomas.
CONCLUSIONS
The CD44s and CD44v6 expression showed a significant relationship with gastric carcinogenesis, toward an aggressive biologic behavior.

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