Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections.
Immunohistochemical loss of keratin (K)13 is one of the most valuable diagnostic criteria for discriminating carcinoma in situ (CIS) from non-malignancies in the oral mucosa while K13 is stably immunolocalized in the prickle cells of normal oral epithelium. To elucidate the molecular mechanism for the loss of K13, we compared the immunohistochemical profiles for K13 and K16 which is not expressed in normal epithelia, but instead enhanced in CIS, with their mRNA levels by in-situ hybridization in formalin-fixed paraffin sections prepared from 23 CIS cases of the tongue, which were surgically removed. Reverse transcriptase-PCR was also performed using RNA samples extracted from laser-microdissected epithelial fragments of the serial paraffin sections in seven of the cases. Although more enhanced expression levels for K16 were confirmed at both the protein and gene levels in CIS in these seven cases, the loss of K13 was associated with repressed mRNA levels in four cases, but not in the other three cases. The results suggest that the loss of K13 is partly due to its gene repression, but may also be due to some unknown post-translational events.
Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Hiroko
H
Ida-Yonemochi
Satoshi
S
Maruyama
Takanori
T
Kobayashi
Manabu
M
Yamazaki
Jun
J
Cheng
Takashi
T
Saku
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007564:Japan; D053535:Keratin-13 / Q000032:analysis* / Q000235:genetics*; D053536:Keratin-16 / Q000032:analysis / Q000235:genetics; D061346:Laser Capture Microdissection; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
D014408:Biomarkers, Tumor; C507426:KRT13 protein, human; C507431:KRT16 protein, human; D053535:Keratin-13; D053536:Keratin-16; D012333:RNA, Messenger