Oncogene profile of papillary thyroid carcinoma

被引:51
作者
Sugg, SL
Ezzat, S
Zheng, L
Freeman, JL
Rosen, IB
Asa, SL
机构
[1] Mt Sinai Hosp, Dept Surg, Toronto, ON M5G 1X5, Canada
[2] Mt Sinai Hosp, Dept Otolaryngol, Toronto, ON M5G 1X5, Canada
[3] Mt Sinai Hosp, Dept Pathol, Toronto, ON M5G 1X5, Canada
[4] Univ Toronto, Wellesley Hosp, Dept Med, Toronto, ON M4Y 1J3, Canada
关键词
D O I
10.1067/msy.2099.92118
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Our purpose was to study the expression of multiple oncogenes in papillary thyroid cancer for possible interactions and prognostic significance. Methods. Twenty papillary thyroid carcinomas were studied for expression/mutation of 3 oncogenes: ras; ret/PTC, and erbB-2/neu. H, N, and K ras codons were examined by polymerase chain reaction (PCR), single-stranded conformation polymorphism and sequencing. The thyroid oncogene ret/PTC was identified by reverse transcription (RT)-PCR Gene amplification of erbB-2/neu was analyzed by differential PCR. The transmembrane domain of erbB-2/neu was sequenced for activating mutations. Quantitation of erbB-2/neu mRNA was evaluated by competitive RT-PCR, and protein expression was determined by immunohistochemistry. Results. Among 20 tumors, 3 had insular/anaplastic dedifferentiation, 13 were intrathyroidal, and 7 were metastatic to cervical lymph nodes (6) or lung (I). An W-ras 13 mutation was found in I metastatic tumor and an N-ras 61 mutation in I intrathyroidal tumor ret/PTC was identified in 3 intrathyroidal and 5 metastatic tumors. No erbB-2/neu DNA amplification or mutations were identified, although 4 tumors had elevated erbB-2/neu mRNA levels. Three of 20 patients had abnormalities detected in multiple oncogenes; 2 had elevated erbB-2/neu mRNA and ret/PTC rearrangements, and I of these had pulmonary metastasis. An intrathyroidal papillary cancer had an N61 ras mutation and a ret/PTC gene rearrangement. Conclusions. ret/PTC rearrangements are present in 40% of papillary thyroid carcinomas and may play a role in metastatic behavior In contrast, ras mutations are rare (10%). erbB-2/neu gene amplification and activating mutations are not detected although elevated mRNA levels were found in 20% of papillary carcinomas. The lack of correlation among the 3 oncogenes in 17 of 20 (85%) papillary thyroid carcinomas suggests that they were not cumulative factors in the pathogenesis of these tumors.
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页码:46 / 52
页数:7
相关论文
共 33 条
[1]   EXPRESSION OF ONCOGENES IN THYROID-TUMORS - COEXPRESSION OF C-ERBB2/NEU AND C-ERBB [J].
AASLAND, R ;
LILLEHAUG, JR ;
MALE, R ;
JOSENDAL, O ;
VARHAUG, JE ;
KLEPPE, K .
BRITISH JOURNAL OF CANCER, 1988, 57 (04) :358-363
[2]  
[Anonymous], 1990, Surgical pathology of the thyroid
[3]   ANALYSIS OF CERBB2 EXPRESSION USING A PANEL OF 6 COMMERCIALLY AVAILABLE ANTIBODIES [J].
BUSMANIS, I ;
FELEPPA, F ;
JONES, A ;
MCGRATH, KM ;
REED, R ;
COLLINS, J ;
RUSSELL, I ;
BEGLEY, CG .
PATHOLOGY, 1994, 26 (03) :261-267
[4]   NCL-CB11, A NEW MONOCLONAL-ANTIBODY RECOGNIZING THE INTERNAL DOMAIN OF THE C-ERBB-2 ONCOGENE PROTEIN EFFECTIVE FOR USE ON FORMALIN-FIXED, PARAFFIN-EMBEDDED TISSUE [J].
CORBETT, IP ;
HENRY, JA ;
ANGUS, B ;
WATCHORN, CJ ;
WILKINSON, L ;
HENNESSY, C ;
GULLICK, WJ ;
TUZI, NL ;
MAY, FEB ;
WESTLEY, BR ;
HORNE, CHW .
JOURNAL OF PATHOLOGY, 1990, 161 (01) :15-25
[5]  
DOUGALL WC, 1994, ONCOGENE, V9, P2109
[6]   The c-erbB-2/neu proto-oncogene in human pituitary tumours [J].
Ezzat, S ;
Zheng, L ;
Smyth, HS ;
Asa, SL .
CLINICAL ENDOCRINOLOGY, 1997, 46 (05) :599-606
[7]   Prevalence of activating ras mutations in morphologically characterized thyroid nodules [J].
Ezzat, S ;
Zheng, L ;
Kolenda, J ;
Safarian, A ;
Freeman, JL ;
Asa, SL .
THYROID, 1996, 6 (05) :409-416
[8]  
FRYE RA, 1989, ONCOGENE, V4, P1153
[9]  
GRIECO D, 1995, ONCOGENE, V11, P113
[10]   Activated neu induces rapid tumor progression [J].
Guy, CT ;
Cardiff, RD ;
Muller, WJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7673-7678