Jun activation domain-binding protein 1 expression in malignant lymphoma of the thyroid: its linkage to degree of malignancy and p27 expression.
BACKGROUND
Jab1 (Jun activation domain-binding protein 1) is known as a coactivator of the AP1 transcription factor, which contributes to carcinoma progression by degrading the p27/Kip1 protein. To date, the clinical significance of jab1 in human carcinoma, including malignant lymphoma, has not been studied in depth. In this study, we investigated jab1 expression in malignant lymphoma of the thyroid.


METHODS
We immunohistochemically studied jab1 expression for 50 cases of thyroid lymphoma, as well as 10 cases of chronic thyroiditis.


RESULTS
Although jab1 was only occasionally expressed in follicular cells in normal follicules, it was diffusely positive in those forming small follicules typical of chronic thyroiditis and malignant lymphoma. In infiltrating lymphocytes in chronic thyroiditis, jab1 was not overexpressed. On the other hand, in malignant lymphomas, jab1 overexpression was observed in 24 cases (48.0%). It was directly linked to MIB-1 labeling index (p < 0.0001), grade of malignancy (p = 0.0130) and aberrant p53 expression (p = 0.0145). Furthermore, an inverse relationship was observed between jab1 and p27 overexpression (p = 0.0130).


CONCLUSIONS
These results suggest that: 1) jab1 plays a role in the regenerating of follicular cells attacked by lymphocytes in chronic thyroiditis and malignant lymphoma, and 2) jab1 contributes to the progression of malignant lymphoma especially with aggressive phenotypes, possibly by degrading p27.
Ito
Yasuhiro
Y
Department of Surgery, Kuma Hospital, 8-2-35, Shimoyamate-dori, Chuo-ku, Kobe 650-0011, Japan. ito01@kuma-h.or.jp
Yoshida
Hiroshi
H
Matsuzuka
Fumio
F
Matsuura
Nariaki
N
Nakamura
Yasushi
Y
Nakamine
Hirokazu
H
Kakudo
Kennichi
K
Kuma
Kanji
K
Miyauchi
Akira
A
D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology; D010447:Peptide Hydrolases; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex