Absence of the BRAF mutation in HBME1+ and CK19+ atypical cell clusters in Hashimoto thyroiditis: supportive evidence against preneoplastic change.

Abstract

An association between Hashimoto thyroiditis and papillary thyroid carcinoma has been postulated for decades. We undertook this study to identify potential precursors of papillary thyroid carcinoma in Hashimoto thyroiditis using a combination of morphologic, immunohistochemical, and molecular techniques. For the study, samples from 59 cases of Hashimoto thyroiditis were stained with antibodies to HBME1 and cytokeratin (CK)19. Tiny HBME1+ and CK19+ atypical cell clusters were identified and analyzed for the BRAF mutation by the colorimetric Mutector assay and allele-specific polymerase chain reaction. HBME1+ and CK19+ atypical cell clusters were identified in 12 (20%) of 59 cases. The minute size (<1 mm) of the clusters and the incomplete nuclear changes precluded a diagnosis of papillary microcarcinoma. The atypical cell clusters from all 12 cases were negative for BRAF. The absence of the BRAF mutation in these atypical cell clusters suggests that they may not be preneoplastic. Caution should be exercised in interpreting positive HBME1 or CK19 staining in Hashimoto thyroiditis.

• Authors: Michel R Nasr, Sanjay Mukhopadhyay, Shengle Zhang, Anna-Luise A Katzenstein
• Journal: American journal of clinical pathology (Am J Clin Pathol) Vol. 132 Issue 6 Pg. 906-12 (Dec 2009) ISSN: 1943-7722 [Electronic] England
• PMID: 19926583 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• DNA, Neoplasm
• HBME-1 antigen
• Keratin-19
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Adenocarcinoma, Papillary (genetics, metabolism, pathology)
• Biomarkers, Tumor (metabolism)
• DNA Mutational Analysis
• DNA, Neoplasm (analysis)
• Diagnosis, Differential
• Hashimoto Disease (genetics, metabolism, pathology)
• Humans
• Keratin-19 (metabolism)
• Mutation
• Precancerous Conditions (genetics, metabolism, pathology)
• Proto-Oncogene Proteins B-raf (genetics, metabolism)
• Thyroid Neoplasms (genetics, metabolism, pathology)