Activation of PI3K-AKT pathway in oral epithelial dysplasia and early cancer of tongue.
Increasingly, cancers are being diagnosed at an early stage. Leukoplakia, a precancerous lesion, progresses to cancer in 5-10% of cases. We performed genetic analysis using cDNA microarray and immunohistochemistry in 6 patients, 3 with precancerous lesions and 3 with early tongue cancer, to evaluate the usefulness of these methods in the diagnosis of precancerous lesions and early cancer. Samples of normal epithelium, epithelial dysplasia, and cancer tissues were collected by laser microdissection, RNA was extracted, and the signals converted to numerical values. Immunohistochemical analysis was performed using antibody against phospho AKT (p-AKT), a component of the phosphoinositide 3-kinase (PI3K) signal pathway. Five genes showed a 2 times or greater level of increase in expression in epithelial tissue in comparison with in normal tissue, while 4 genes showed a 2 times or greater increase in early cancer tissues. In cancer tissues and epithelial dysplasia tissues, PI3K class III was expressed at 2.5 times and 11 times the level of that found in normal tissue, respectively. Histochemistry using p-AKT antibody revealed no positive cells in normal tissue. Positive cells were noted in the basal and parabasal cell layers, and partially in the spinous layer of epithelial dysplasia tissues, and in the spinous layer of early cancer tissues. These findings suggest that activation of the PI3K-AKT signal pathway is associated with oral carcinogenesis.
Watanabe
Shinya
S
Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba 272-8513, Japan. swtnabe@tdc.ac.jp
Sato
Kazumichi
K
Okazaki
Yuichiro
Y
Tonogi
Morio
M
Tanaka
Yoichi
Y
Yamane
Gen-yuki
GY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D055088:Early Detection of Cancer; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007972:Leukoplakia, Oral / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
C096816:BCL2-related protein A1; D014408:Biomarkers, Tumor; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt