RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes

Follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma

Kerry J. Rhoden, Kristian Unger, Giuliana Salvatore, Yesim Yilmaz, Volodymyr Vovk, Gennaro Chiappetta, Mazin B. Qumsiyeh, Jay L. Rothstein, Alfredo Fusco, Massimo Santoro, Horst Zitzelsberger, Giovanni Tallini

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Context: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid carcinoma, but its specificity has been questioned because of the disputed identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and other thyroid lesions. Objective: The objective of this study was to determine 1) whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its recombination rate in thyroid tumors. Design/Patients: Forty-three samples from 31 cases of HT were examined using interphase fluorescence in situ hybridization (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser capture microdissection to enrich samples for follicular cells. The results were compared with those similarly obtained in 34 papillary carcinomas, eight thyroid oncocytic tumors, and 21 normal thyroids. Results: Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26% (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. Conclusions: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.

Original languageEnglish
Pages (from-to)2414-2423
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number6
DOIs
Publication statusPublished - 2006

Fingerprint

Hashimoto Disease
Papillary Carcinoma
Genetic Recombination
Tumors
Microdissection
Fluorescence
Thyroid Gland
Thyroiditis
Fluorescence In Situ Hybridization
Laser Capture Microdissection
Lasers
Real-Time Polymerase Chain Reaction
Neoplasms
Cells
Messenger RNA
Papillary Thyroid cancer
Thyroid Epithelial Cells
Interphase
Inflammation
Carcinoma

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes : Follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma. / Rhoden, Kerry J.; Unger, Kristian; Salvatore, Giuliana; Yilmaz, Yesim; Vovk, Volodymyr; Chiappetta, Gennaro; Qumsiyeh, Mazin B.; Rothstein, Jay L.; Fusco, Alfredo; Santoro, Massimo; Zitzelsberger, Horst; Tallini, Giovanni.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 6, 2006, p. 2414-2423.

Research output: Contribution to journalArticle

Rhoden, Kerry J. ; Unger, Kristian ; Salvatore, Giuliana ; Yilmaz, Yesim ; Vovk, Volodymyr ; Chiappetta, Gennaro ; Qumsiyeh, Mazin B. ; Rothstein, Jay L. ; Fusco, Alfredo ; Santoro, Massimo ; Zitzelsberger, Horst ; Tallini, Giovanni. / RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes : Follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 6. pp. 2414-2423.
@article{7097af8939ba4fd6a2438dcc48e1ddcf,
title = "RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: Follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma",
abstract = "Context: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid carcinoma, but its specificity has been questioned because of the disputed identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and other thyroid lesions. Objective: The objective of this study was to determine 1) whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its recombination rate in thyroid tumors. Design/Patients: Forty-three samples from 31 cases of HT were examined using interphase fluorescence in situ hybridization (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser capture microdissection to enrich samples for follicular cells. The results were compared with those similarly obtained in 34 papillary carcinomas, eight thyroid oncocytic tumors, and 21 normal thyroids. Results: Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17{\%} (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26{\%} (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. Conclusions: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.",
author = "Rhoden, {Kerry J.} and Kristian Unger and Giuliana Salvatore and Yesim Yilmaz and Volodymyr Vovk and Gennaro Chiappetta and Qumsiyeh, {Mazin B.} and Rothstein, {Jay L.} and Alfredo Fusco and Massimo Santoro and Horst Zitzelsberger and Giovanni Tallini",
year = "2006",
doi = "10.1210/jc.2006-0240",
language = "English",
volume = "91",
pages = "2414--2423",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes

T2 - Follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma

AU - Rhoden, Kerry J.

AU - Unger, Kristian

AU - Salvatore, Giuliana

AU - Yilmaz, Yesim

AU - Vovk, Volodymyr

AU - Chiappetta, Gennaro

AU - Qumsiyeh, Mazin B.

AU - Rothstein, Jay L.

AU - Fusco, Alfredo

AU - Santoro, Massimo

AU - Zitzelsberger, Horst

AU - Tallini, Giovanni

PY - 2006

Y1 - 2006

N2 - Context: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid carcinoma, but its specificity has been questioned because of the disputed identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and other thyroid lesions. Objective: The objective of this study was to determine 1) whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its recombination rate in thyroid tumors. Design/Patients: Forty-three samples from 31 cases of HT were examined using interphase fluorescence in situ hybridization (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser capture microdissection to enrich samples for follicular cells. The results were compared with those similarly obtained in 34 papillary carcinomas, eight thyroid oncocytic tumors, and 21 normal thyroids. Results: Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26% (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. Conclusions: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.

AB - Context: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid carcinoma, but its specificity has been questioned because of the disputed identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and other thyroid lesions. Objective: The objective of this study was to determine 1) whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its recombination rate in thyroid tumors. Design/Patients: Forty-three samples from 31 cases of HT were examined using interphase fluorescence in situ hybridization (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser capture microdissection to enrich samples for follicular cells. The results were compared with those similarly obtained in 34 papillary carcinomas, eight thyroid oncocytic tumors, and 21 normal thyroids. Results: Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26% (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. Conclusions: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.

UR - http://www.scopus.com/inward/record.url?scp=33744962523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744962523&partnerID=8YFLogxK

U2 - 10.1210/jc.2006-0240

DO - 10.1210/jc.2006-0240

M3 - Article

VL - 91

SP - 2414

EP - 2423

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -