Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas

被引:34
作者
Puxeddu, E
Moretti, S
Giannico, A
Martinelli, M
Marino, C
Avenia, N
Cristofani, R
Farabi, R
Reboldi, G
Ribacchi, R
Pontecorvi, A
Santeusanio, F
机构
[1] Univ Perugia, Dipartimento Med Interna, Sez Med Interna & Sci Endocrine & Metab, I-06126 Perugia, Italy
[2] Univ Perugia, Chair Pathol 2, I-06126 Perugia, Italy
[3] Univ Perugia, Dept Surg Sci, I-06126 Perugia, Italy
[4] Univ Perugia, Inst Pathol R, I-06126 Perugia, Italy
[5] Catholic Univ, Regina Elena Canc Inst, Lab Mol Oncogenesis, Rome, Italy
[6] Catholic Univ, Inst Med Pathol, Rome, Italy
关键词
D O I
10.1530/eje.0.1480505
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: RET proto-oncogene rearrangements (ret/PTCs) represent the most common genetic alterations found in papillary thyroid carcinomas (PTCs). Correlation of ret/PTC expression with clinical outcome is controversial. The aim of the present study was to analyze the frequency of RET rearrangements in adult PTCs, and to investigate if ret/PTCs influence biological behavior and clinical features of the cancers. Design: Ret/PTC rearrangements were looked for in tissue samples of 48 PTCs collected at our institution. Data about clinical and pathological features of the tumors were also reviewed. Three separate association analyses were carried out on the cohort evaluating the effects of, respectively, ret/PTC positivity, preferential RET tyrosine kinase domain (RET-TK) expression, and ret/PTC plus RET-TK positivity, on age, sex, tumor size, staging, number of neoplastic foci, and histological subtype. Methods: The genetic study was conducted with the RT-PCR-Southern blot technique. Standard Student's t-test and Fisher exact test were applied for the association analyses. Results: The molecular genetic study demonstrated the positivity of ret/PTC1 and ret/PTC3 in 13 of 48 tumors (27.1%), and an exclusive or preferential RET-TK expression in 17 cases (35.4%). None of the three genetico-clinical analyses showed any significant association between ret/PTC expression and the clinical and pathological features of the cancers. Conclusions: These data indicate that RET rearrangements may not play any distinctive role in driving histotype development and cancer progression in these neoplasms. Moreover, they weaken the possibility of using ret/PTC as a prognostic marker for papillary thyroid carcinomas.
引用
收藏
页码:505 / 513
页数:9
相关论文
共 37 条
[1]  
Bongarzone I, 1998, CLIN CANCER RES, V4, P223
[2]   MOLECULAR CHARACTERIZATION OF A THYROID TUMOR-SPECIFIC TRANSFORMING SEQUENCE FORMED BY THE FUSION OF RET TYROSINE KINASE AND THE REGULATORY SUBUNIT RI-ALPHA OF CYCLIC AMP-DEPENDENT PROTEIN KINASE-A [J].
BONGARZONE, I ;
MONZINI, N ;
BORRELLO, MG ;
CARCANO, C ;
FERRARESI, G ;
ARIGHI, E ;
MONDELLINI, P ;
DELLAPORTA, G ;
PIEROTTI, MA .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (01) :358-366
[3]  
BONGARZONE I, 1994, CANCER RES, V54, P2979
[4]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[5]   DIFFERENTIATION OF T-CELL LYMPHOKINE GENE-EXPRESSION - THE INVITRO ACQUISITION OF T-CELL MEMORY [J].
EHLERS, S ;
SMITH, KA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (01) :25-36
[6]   RET/PTC rearrangements in thyroid nodules: Studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults [J].
Elisei, R ;
Romei, C ;
Vorontsova, T ;
Cosci, B ;
Veremeychik, V ;
Kuchinskaya, E ;
Basolo, F ;
Demidchik, EP ;
Miccoli, P ;
Pinchera, A ;
Pacini, F .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (07) :3211-3216
[7]   Expression and alternative splicing of c-ret RNA in papillary thyroid carcinomas [J].
Fluge, O ;
Haugen, DRF ;
Akslen, LA ;
Marstad, A ;
Santoro, M ;
Fusco, A ;
Varhaug, JE ;
Lillehaug, JR .
ONCOGENE, 2001, 20 (07) :885-892
[8]   PTC IS A NOVEL REARRANGED FORM OF THE RET PROTO-ONCOGENE AND IS FREQUENTLY DETECTED INVIVO IN HUMAN THYROID PAPILLARY CARCINOMAS [J].
GRIECO, M ;
SANTORO, M ;
BERLINGIERI, MT ;
MELILLO, RM ;
DONGHI, R ;
BONGARZONE, I ;
PIEROTTI, MA ;
DELLAPORTA, G ;
FUSCO, A ;
VECCHIO, G .
CELL, 1990, 60 (04) :557-563
[9]  
JHIANG SM, 1992, ONCOGENE, V7, P1331
[10]   DEVELOPMENT OF A SINGLE-STEP DUPLEX RT-PCR DETECTING DIFFERENT FORMS OF RET ACTIVATION, AND IDENTIFICATION OF THE 3RD FORM OF IN-VIVO RET ACTIVATION IN HUMAN PAPILLARY THYROID-CARCINOMA [J].
JHIANG, SM ;
SMANIK, PA ;
MAZZAFERRI, EL .
CANCER LETTERS, 1994, 78 (1-3) :69-76