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E Saggiorato
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M Papotti
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( Baloch et al. 2002 , Castro & Gharib 2003 ). Moreover, the cytological diagnosis of a follicular variant of papillary carcinoma represents an additional problem, since the diagnostic cytological criteria of papillary carcinoma (cytoplasmic

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Isabel Amendoeira Department of Pathology, Centro Hospitalar S. João, Porto, Portugal
Department of Pathology, Medical Faculty of the University of Porto, Porto, Portugal
Ipatimup – Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

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Tiago Maia Department of Pathology, Centro Hospitalar S. João, Porto, Portugal
Department of Pathology, Medical Faculty of the University of Porto, Porto, Portugal

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Manuel Sobrinho-Simões Department of Pathology, Centro Hospitalar S. João, Porto, Portugal
Department of Pathology, Medical Faculty of the University of Porto, Porto, Portugal
Ipatimup – Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
I3S – Institute of Investigation and Innovation in Health, Porto, Portugal

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, follicular adenoma (FA) or follicular carcinoma (FTC) for encapsulated follicular-patterned lesions, the latter if capsular and/or vascular invasion was present, and papillary carcinomas for tumors displaying papillae formation. Later, Lindsay first ( Lindsay

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Maria Rosaria Rusciano Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Marcella Salzano Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Sara Monaco Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Maria Rosaria Sapio Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Maddalena Illario Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Valentina De Falco Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Massimo Santoro Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Pietro Campiglia Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Lucio Pastore Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy
Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Gianfranco Fenzi Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Guido Rossi Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy
Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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Mario Vitale Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy
Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

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experiment, single individual cultures were used. The TAD-2 cell line, obtained by Simian virus 40 infection of human fetal thyroid cells. was generously donated by Dr T F Davies (Mount Sinai, New York, NY, USA). Thyroid papillary carcinoma cell lines TPC-1

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N Garcia de la Torre
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I Buley
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J A H Wass
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H E Turner
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), diffuse Hy due to Graves’ disease (22), follicular adenoma (FA) (54), papillary carcinoma (PC) (27), PMC (8), follicular carcinoma (FC) (20), MC (8) and normal thyroid (NT) tissue (19). Samples of NT tissue came from patients with a previous

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J M Gómez
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N Gómez
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M Sahún
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A Rafecas
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C Villabona
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J Soler
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Abstract

Despite the usual excellent prognosis of differentiated thyroid carcinoma, some patients die because of disease. It has been speculated that lethal disease may have a better prognosis if patients are treated with extensive surgery plus 131I ablative treatment. We have analyzed a group of 223 patients with differentiated thyroid carcinoma treated under a uniform therapeutic protocol of surgery and followed for 3 to 17.7 years, in order to differentiate patients with a high and a low risk of mortality and the influence of therapy on survival rate.

The therapeutic protocol was as follows. If the diagnosis was papillary carcinoma, subtotal thyroidectomy was performed and cervical nodes were removed if they were suspicious for cancer. If the diagnosis was follicular carcinoma, a total thyroidectomy was performed. 131I was given in cases of patients who were more than 60 years old or who had extrathyroid disease or metastases in papillary carcinomas and in macroangioinvasive follicular carcinomas. In survival analysis, the event used as the end-point was death due to thyroid carcinoma and summarized by the Kaplan-Meier curve and the Mantel-Cox method.

We found three independent prognostic factors which determined mortality: over 60 years of age, tumor size larger than 6 cm and metastases. On the basis of these factors we identified two risk groups: a low-risk group (A), who had no risk factors, composed of 153 patients whose survival rate at 205 months was 100% and a high-risk group (B), who had one or more risk factors, composed of 55 patients whose survival rate at 213 months was 39.6%. Seventeen patients in this second group died from thyroid carcinoma. We therefore analyzed the effect of treatment in group B. Patients who had more extensive surgery had a similar survival rate to those who had less extensive surgery and 131I administration did not modify the survival rate.

These data support the idea that the identification of low-risk groups may facilitate a more rational approach to treatment of differentiated thyroid carcinoma, avoiding aggressive therapy in cases with a good prognosis.

Endocrine-Related Cancer (1997) 4 459-464

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Raffaele Ciampi
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Thomas J Giordano
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Kathryn Wikenheiser-Brokamp
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Ronald J Koenig
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Yuri E Nikiforov
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pathway have been demonstrated to be crucial in the pathogenesis of papillary carcinomas, as they are found in more than 70% of all tumors and rarely overlap in the same tumor, suggesting that activation of a single effector of this pathway is sufficient

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Monica Fedele Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Dario Palmieri Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Gennaro Chiappetta Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Rosa Pasquinelli Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Ivana De Martino Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Claudio Arra Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Giuseppe Palma Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Teresa Valentino Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Giovanna M Pierantoni Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Giuseppe Viglietto Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Jay L Rothstein Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Massimo Santoro Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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Alfredo Fusco Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

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.4% of tumors ( Vasko et al . 2003 ). K-RAS mutations in exon 1 were found more often in papillary carcinomas ( De Micco 2003 ). The genetic lesions described above are mutually exclusive, since no tumors have been found bearing more than one of these

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J Di Cristofaro
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V Vasko
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V Savchenko
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S Cherenko
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A Larin
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M D Ringel
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M Saji
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M Marcy
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J F Henry
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P Carayon
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C De Micco
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heterogeneous tumor class and that some are composed of cell populations with different molecular oncogenic processes ( Ishizaka et al. 1991 , Vasko et al. 2003 ). In thyroid nodules with incomplete morphological features of papillary carcinoma, ret

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Sonia Cheng Department of Pathology, Servicio de Endocrinología, Department of Medicine, University Health Network and the Ontario Cancer Institute, 200 Elizabeth Street, 11th Floor, Toronto, Ontario, Canada M5G 2C4
Department of Pathology, Servicio de Endocrinología, Department of Medicine, University Health Network and the Ontario Cancer Institute, 200 Elizabeth Street, 11th Floor, Toronto, Ontario, Canada M5G 2C4

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Wei Liu Department of Pathology, Servicio de Endocrinología, Department of Medicine, University Health Network and the Ontario Cancer Institute, 200 Elizabeth Street, 11th Floor, Toronto, Ontario, Canada M5G 2C4

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Moises Mercado Department of Pathology, Servicio de Endocrinología, Department of Medicine, University Health Network and the Ontario Cancer Institute, 200 Elizabeth Street, 11th Floor, Toronto, Ontario, Canada M5G 2C4

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Shereen Ezzat Department of Pathology, Servicio de Endocrinología, Department of Medicine, University Health Network and the Ontario Cancer Institute, 200 Elizabeth Street, 11th Floor, Toronto, Ontario, Canada M5G 2C4

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Sylvia L Asa Department of Pathology, Servicio de Endocrinología, Department of Medicine, University Health Network and the Ontario Cancer Institute, 200 Elizabeth Street, 11th Floor, Toronto, Ontario, Canada M5G 2C4

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metastatic sample; 45% were Stage T1, 56.8% were classified as papillary (including micropapillary), and 37.71% were follicular variant papillary carcinoma. Clinical and pathological variables From the 375 patients with complete clinical and pathologic

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Koji Sakamoto Department of Otorhinolaryngology, Saiseikai Utsunomiya Hospital, Utsunomiya City, Tochigi, Japan
Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Hiroyuki Ozawa Department of Otorhinolaryngology, Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan

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Yoichiro Sato Department of Otorhinolaryngology, Saiseikai Utsunomiya Hospital, Utsunomiya City, Tochigi, Japan

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Masashi Nakaishi Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Atsuko Sakanushi Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Takeshi Matsunobu Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Kimihiro Okubo Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Seiichi Shinden Department of Otorhinolaryngology, Saiseikai Utsunomiya Hospital, Utsunomiya City, Tochigi, Japan

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ectopic thyroid gland of the lateral neck. Patients sometimes present with a single cystic metastasis from occult primary papillary carcinoma, which is difficult to distinguish from lateral cervical cysts with imaging studies and FNAC; however, the

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