Expression of down stream molecules of RET (p-ERK, p-p38 MAPK, p-JNK and p-AKT) in papillary thyroid carcinomas.
To evaluate the roles of 4 putative downstream molecules (ERK, p38 MAPK, JNK and AKT) of the RET signal pathway in the tumorigenesis of papillary carcinomas, the expression patterns of RET and phosphorylated forms of ERK, p38 MAPK, JNK and AKT were evaluated in 115 cases of papillary thyroid carcinomas by 3 mm-core tissue microarray based immunohistochemical staining. The prevalence of RET protein expression was 62.6%. No distinct expression of p-ERK and p-p38 MAPK was demonstrated in tumor cells of papillary carcinomas. All papillary carcinomas except 5 cases expressed nuclear p-JNK and p-JNK expression was increased in tumors compared with paired normal tissues (p < 0.05). There was no difference in the p-JNK expression between RET protein-positive and RET protein-negative papillary carcinomas (p > 0.05). Unequivocal nuclear staining for p-AKT was demonstrated only in 10 cases of papillary carcinomas, and all of them showed focal staining. Our results showing constitutive expression of p-JNK in most cases of surgically excised papillary thyroid carcinomas irrespective of RET protein expression status suggest that JNK activation may play a role in the tumorigenesis or survival of sporadic papillary thyroid carcinoma.
Shin
Eunah
E
Department of Pathology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. wiyang9660@yumc.yonsei.ac.kr
Hong
Soon-Won
SW
Kim
Se Hoon
SH
Yang
Woo-Ick
WI
D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases
D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases