Alteration of CD44E Expression in Gastric Carcinogenesis and Lymph Node Metastasis

Park, Cho Hyun; Kang, Won Kyung; Hong, Young Seon; Kim, In Chul

Abstract

CD44 is a heterogenous group of cell surface glycoprotein that serves as an adhesion molecule in cell-cell and cell-matrix interactions involving lymphocyte homing, cell migration, and cancer metastasis. CD44 exists at least 20 variants due to alternative splicing of 10 exons(v1-v10) which encode the membrane proximal portion of extracellular domain. It has been reported that malignant transformation is associated with alteration in CD44 alternative splicing that results in a down-regulation of CD44H relative to several other CD44 variant transcripts and overexpression of specific CD44 alternative splice variants on tumor cells has resulted in enhanced metastatic potential. In this study we investigate the expression of CD44 in 21 sets of gastric carcinoma tissue, adjacent noncancerous gastric mucosa and metastatic lymph node by RT-PCR(reverse transcription-polymerase chain reaction) and immunohistochemical staining to elucidate the alteration of CD44 expression during transformation of normal gastric mucosa to carcinoma and lymph node metastasis. In immunohistochemical staining using anti-CD44 antibody BMS113BT which recognize epitopes in the extracellular domain of CD44 molecules, CD44 expression was not demonstrated in normal gastric mucosa. However, 9(64.3%) out of 14 gastric cancer specimens and 9(75.0%) out of 12 metastatic lymph nodes revealed strong reactivity to CD44. In RT-PCR, epithelial variant, CD44E was amplified in 14(66.7%) of 21 gastric cancer specimens and 13(61.9%) of 21 metastatic lymph nodes, whereas 4(19.0%) of 21 normal gastric mucosal tissues. According to Lauren's classification, CD44E was amplified in all of 6 diffuse type gastric carcinomas compared to 8(61.5%) of 13 intestinal type carcinomas(p=0.227). Amplification of CD44E was not correlated with tumor stage or vascular invasion. Eight(38.1%) out of 21 cases demonstrated amplification of CD44E both in primary tumor and metastatic lymph node. Five(23.8%) cases showed amplification of CD44E only in metastatic lymph node. We suggest that the expression of CD44E is strongly related with gastric carcinogenensis, especially in diffuse type carcinomas. PCR amplification of CD44E in premalignant lesions may be useful to predict risk of malignant transformation in molecular level. However, role of CD44E in lymph node metastasis of gastric carcinoma is remained to be solved.