CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: CD44 protein is known as a homing cellular adhesion molecule that is linked to di-verse cellular functions such as adhesion, migration and invasion, which are all important in can-cer 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 expres¬sion 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 Inter-national 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 out¬come in tumor stage III in DLBCL patients.
Abstract
Background: CD44 protein is known as a homing cellular adhesion molecule that is linked to di-verse cellular functions such as adhesion, migration and invasion, which are all important in can-cer 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 expres¬sion 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 Inter-national 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 out¬come in tumor stage III in DLBCL patients.
참고문헌 (26)
- "A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project", N Engl J Med, 329, pp.987~994 (1993)
- 김진만, "WHO Classification of Malignant Lymphomas in Korea: Report of the Third Nationwide Study", The Korean Journal of Pathology, 45(3), pp.254~260 (2011), 대한병리학회
- "A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project", Blood, 89, pp.3909~3918 (1997)
- Alizadeh AA, "Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling", Nature, 403, pp.503~511 (2000)
- Rosenwald A, "The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma", N Engl J Med, 346, pp.1937~1947 (2002)
- Hans CP, "Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray", Blood, 103, pp.275~282 (2004)
- Naor D, "CD44: structure, function, and association with the malignant process", Adv Cancer Res, 71, pp.241~319 (1997)
- Rudzki Z, "CD44 and the adhesion of neoplastic cells", Mol Pathol, 50, pp.57~71 (1997)
- Stauder R, "CD44 variant isoforms in non-Hodgkin’s lymphoma: a new independent prognostic factor", Blood, 85, pp.2885~2899 (1995)
- Terpe HJ, "Expression of integrins and CD44 isoforms in non-Hodgkin’s lymphomas: CD44 variant isoforms are preferentially expressed in high-grade malignant lymphomas", J Pathol, 174, pp.89~100 (1994)
- Salles G, "Alternatively spliced CD44 transcripts in diffuse large-cell lymphomas: characterization and comparison with normal activated B cells and epithelial malignancies", Blood, 82, pp.3539~3547 (1993)
- Tzankov A, "Prognostic significance of CD44 expression in diffuse large B cell lymphoma of activated and germinal centre B cell-like types: a tissue microarray analysis of 90 cases", J Clin Pathol, 56, pp.747~752 (2003)
- Shipp MA, "Can we improve upon the International Index", Ann Oncol, 8(Suppl 1), pp.43~47 (1997)
- Aruffo A, "CD44 is the principal cell surface receptor for hyaluronate", Cell, 61, pp.1303~1313 (1990)
- Lesley J, "CD44 and its interaction with extracellular matrix", Adv Immunol, 54, pp.271~335 (1993)
- Marhaba R, "CD44 in cancer progression: adhesion, migration and growth regulation", J Mol Histol, 35, pp.211~231 (2004)
- Afify A, "Expression of CD44s, CD44v6, and hyaluronan across the spectrum of normal-hyperplasia-carcinoma in breast", Appl Immunohistochem Mol Morphol, 16, pp.121~127 (2008)
- Wang SJ, "CD44 variant isoforms in head and neck squamous cell carcinoma progression", Laryngoscope, 119, pp.1518~1530 (2009)
- Washington K, "Expression of cell adhesion molecule CD44 in primary tumors of the liver: an immunohistochemical study", Liver, 17, pp.17~23 (1997)
- Okimura A, "Immunohistochemical analyses of E-cadherin, beta-catenin, CD44s, and CD44v6 expressions, and Ki-67 labeling index in intraductal papillary mucinous neoplasms of the pancreas and associated invasive carcinomas", Med Mol Morphol, 42, pp.222~229 (2009)
- Jalkanen S, "Lymphocyte homing and clinical behavior of non-Hodgkin’s lymphoma", J Clin Invest, 87, pp.1835~1840 (1991)
- Ristamäki R, "CD44v6 expression in non-Hodgkin’s lymphoma: an association with low histological grade and poor prognosis", J Pathol, 176, pp.259~267 (1995)
- Ristamäki R, "Elevated serum CD44 level is associated with unfavorable outcome in non-Hodgkin’s lymphoma", Blood, 90, pp.4039~4045 (1997)
- Drillenburg P, "CD44 expression predicts disease outcome in localized large B cell lymphoma", Leukemia, 13, pp.1448~1455 (1999)
- Yu Q, "Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function", J Exp Med, 186, pp.1985~1996 (1997)
- Bai Y, "Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin", Oncogene, 26, pp.836~850 (2007)