Expressions of androgen receptor and its co-regulators in carcinoma ex  pleomorphic adenoma of salivary gland.
OBJECTIVE
Androgen receptor (AR) signalling is involved in cancer progression. The expression of AR has been reported in carcinoma ex pleomorphic adenoma (CXPA) of salivary gland, however AR gene status and the expressions of cofactors for AR signalling have not been investigated. The aims of this study were to investigate the expressions of each of the molecules that contribute to AR activation with or without ligands in CXPA. In addition, AR gene amplification and single-nucleotide polymorphism were investigated.


METHODS
Ten cases of CXPA and 23 cases of pleomorphic adenomas (PA) of the salivary glands were immunostained for the AR co-regulators (SRC1, p300, and NCoR1) and the signalling molecules involved in the ligand-independent pathway (i.e., HER-2/neu and STAT3). AR gene amplification and single-nucleotide polymorphism were investigated by dual-coloured fluorescent in situ hybridisation and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), respectively.


RESULTS
AR expression was observed in nine of 10 cases of CXPA and in 30.4% of PA cases, a statistically significant difference. The expression, with low or high intensity, of HER-2/neu and STAT3 was more frequent in CXPA (6/10 and 9/10, respectively) than in PA (0% and 46.7%). The expression of co-activators was also stronger, though only slightly, in CXPA than in PA. The gain of chromosome X and AR gene amplification were not observed in any CXPA or PA cases, and the G --> A allele in codon 211 was detected in only one case (a CXPA).


CONCLUSIONS
These results suggest that although AR may be activated in the pathway with or without ligands, the expression of co-regulators and AR gene aberrations are not involved in the carcinogenesis of CXPA.
Nakajima
Yoriko
Y
Department of Plastic Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan.
Kishimoto
Takashi
T
Nagai
Yuichiro
Y
Yamada
Masatoshi
M
Iida
Yumiko
Y
Okamoto
Yoshitaka
Y
Ishida
Yasuo
Y
Nakatani
Yukio
Y
Ichinose
Masaharu
M
D008949:Adenoma, Pleomorphic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human