Increased midkine expression in intrahepatic cholangiocarcinoma: immunohistochemical and in situ hybridization analyses.
OBJECTIVE
Midkine (MK) is a novel heparin-binding growth factor whose gene was identified in embryonal carcinoma cells in the early stages of retinoic acid-induced differentiation. This study investigates the overexpression of MK in intrahepatic cholangiocarcinoma (CC).


METHODS
Forty-five primary CC specimens from patients (aged 19-81 years, 24 males and 21 females) were examined. Histologically, 17 cases of CC were classified as the well-differentiated type, 19 as moderately-differentiated and 9 as poorly-differentiated. Immunohistochemical analysis was performed using a rat IgG2a monoclonal antibody against the carboxyl terminal region of human MK.


RESULTS
We successfully applied this monoclonal antibody against MK to analyze archival paraffin sections. The cancer tissues showed a positive reaction to this antibody, and there was an intense reaction in their cytoplasm. Approximately 40% of individuals with CC (17/45) had tumor cells that expressed MK, and these were classified into the following types: moderately-differentiated type (9/19), well-differentiated type (8/17) and poorly-differentiated type (0/ 9). In situ hybridization analysis revealed that signals of MK transcripts were found in the cytoplasm of the cancer cells; the distribution and localization of the MK-transcript signals determined by in situ hybridization analysis were similar to those obtained by immunohistochemical analysis.


CONCLUSIONS
These findings revealed that CC express increased MK at the messenger RNA and protein levels.
Kato
M
M
The Second Department of Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Shinozawa
T
T
Kato
S
S
Endo
K
K
Terada
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines; D015342:DNA Probes / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009414:Nerve Growth Factors / Q000378:metabolism*; D012189:Retrospective Studies
D002352:Carrier Proteins; D016207:Cytokines; D015342:DNA Probes; D004273:DNA, Neoplasm; D009414:Nerve Growth Factors; D000078792:Midkine