Expression of peroxisome proliferator-activated receptor gamma, E-cadherin and matrix metalloproteinases-2 in gastric carcinoma and lymph node metastases.
BACKGROUND
Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand-activated transcription factor. Activation of PPARgamma has recently been demonstrated to inhibit various tumor cells growth, progression and metastasis. E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer tissues. Matrix metalloproteinases-2 (MMP-2) is a prerequisite for metastasizing tumor cells. However their correlation is still unknown in gastric carcinoma. The aim of this study was to assess the expression of PPARgamma, E-cadherin, MMP-2 and their correlation in gastric carcinoma and metastases.


METHODS
Gastric carcinoma tissues and their corresponding lymph nodes with metastases and the adjacent non-tumor tissues were obtained from 54 patients with gastric cancer who underwent gastrectomy. Expression of PPARgamma, E-cadherin and MMP-2 was assessed by immunohistochemical staining.


RESULTS
The nuclear expression level of PPARgamma in neoplastic cells was significantly lower than that in the normal controls (P < 0.001), with the expression of PPARgamma being weaker in primary tumors compared with that in metastases. In all neoplastic cells, E-cadherin was expressed with abnormal patterns (cytoplasm pattern, cytoplasm and membrane pattern or absent), compared with normal cells where E-cadherin was expressed with a normal pattern (membrane pattern). Compared with the normal tissues, the expression level of E-cadherin decreased in primary tumors and further decreased in metastases (P < 0.001). Membrane staining of MMP-2 was detected in the foveolar epithelia of normal gastric mucosa, whereas predominant cytoplasm staining of MMP-2 was found in malignant tissues. The expression of MMP-2 was stronger in metastatic tissues than in primary tumors. In neoplastic foci the expression of PPARgamma was negatively correlated with MMP-2 expression (P < 0.05). However, there was no correlation between E-cadherin and PPARgamma or MMP-2 expression.


CONCLUSIONS
Down-regulation of PPARgamma and E-cadherin and up-regulation of MMP-2 in neoplastic foci might be helpful to gastric carcinogenesis and metastases. An inverse relationship between PPARgamma and MMP-2 in human gastric carcinoma suggests that PPARgamma might modulate MMP-2 expression and affect gastric cancer metastases.
He
Qing
Q
Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Chen
Jie
J
Lin
Han-liang
HL
Hu
Pin-jin
PJ
Chen
Min-hu
MH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D008875:Middle Aged; D047495:PPAR gamma / Q000032:analysis*; D013270:Stomach / Q000737:chemistry; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology
D015820:Cadherins; D047495:PPAR gamma; D020778:Matrix Metalloproteinase 2