Relations of CD44 Expression with Metastasis and Prognosis in Osteosarcoma

Kim, Han Soo; Park, Yong Bum; Kim, Chong Jai; Seong, In Ho; Kim, Seong Tae; Lee, Sang Hoon

Abstract

CD44 is a cell surface glycoprotein, which not only functions as a receptor to hyaluronan and other extracelluar matrix ligands but also is implicated in tumorigenesis, growth, invasion and metastasis in several kinds of human malignacies. There has not been any report concerning the relation of CD44 to metastasis or prognostic value in osteosarcoma. In the current study, we evaluated the expression of CD44 standard and CD44v5 and 0D44v6 isoforms immunohistochemically in osteosarcoma and assessed the prognostic value of these cell surface proteins. Formalin-fixed, paraffin-embedded archival pathologic tissues from fifty osteosarcoma patients were collected. Thirty-seven cases were osteoblastic, three chondroblastic, six fibroblastic, three telangiectatic and one mixed type. The immunohistochemical procedures were performed using a biotin-streptavidin detection system with diaminobenzidine chromogen. According to the proportion of stained cells, scores were semiquantitatively graded into three categories; '-', negative; '+', intermediate; and '11' high (more than 50 percent positive cells). We regarded overexpression of CD44 protein in case of 'high' score. Patterns of CD44 immnostaining were mainly membranous with a minor component of cytoplasmic pattern. Overexpression of CD44s was observed in 169o (8/50), that of v5 in 20% (10/50) and that of v5, in 46% (23/50) of osteosarcomas. Among the CD44 isoforms, overexpression of CD44v5 isoform was significantly correlated with metastasis (P=0.004). Survival of CD44v5 positive (overexpressed) group was significantly shorter than CD44v5 negative group(P=0.006). In conclusion, any isoform of CD44s, v5, v6 was not an independent predictor of overall survival, however, overexpression of CD44v5 may be considered one of predictors of poor survival in osteosarcoma as regards with metastasis. Further study is required to confirm its prognostic significance in osteosarcoma with relation to other biological tumor markers.