J Korean Surg Soc.  2013 Jan;84(1):9-17.

Osteopontin expression in papillary thyroid carcinoma and its relationship with the BRAF mutation and tumor characteristics

Affiliations
  • 1Department of Surgery, Chung-Ang University Hospital, Seoul, Korea. poplipss@daum.net

Abstract

PURPOSE
We evaluated the relationship between the degree of osteopontin (OPN) expression in papillary thyroid carcinoma (PTC) specimens and the presence of the BRAF mutation and clinicopathologic variables.
METHODS
Fifty-six snap-frozen thyroid tumor samples, including those of 49 PTCs, four follicular adenomas, two follicular carcinomas, and one Hurthle cell adenoma, were studied. We performed reverse transcription-polymerase chain reaction (RT-PCR) to assess the OPN expression levels. We also tested the BRAF codon 599 mutations using RT-PCR with the direct sequencing method. All of the tumors were microscopically reexamined by a pathologist with a special interest in thyroid neoplasia.
RESULTS
OPN mRNA was significantly overexpressed in the PTC samples compared with other thyroid tumors (P = 0.011). In PTCs, the OPN expression level was higher in the BRAF mutation group than in the wild-type group (P = 0.041). Among the clinicopathologic variables, nonfollicular variant histologic subtypes (P = 0.002) and the presence of lymph node metastases (P = 0.042) were correlated with elevated level of OPN expression.
CONCLUSION
OPN might play a crucial role in tumorigenesis and the progression of PTC.

Keyword

Osteoponin; Papillary thyroid cancer

MeSH Terms

Adenoma
Carcinoma
Cell Transformation, Neoplastic
Codon
Factor IX
Lymph Nodes
Neoplasm Metastasis
Osteopontin
RNA, Messenger
Thyroid Gland
Thyroid Neoplasms
Carcinoma
Codon
Factor IX
Osteopontin
RNA, Messenger
Thyroid Neoplasms

Figure

  • Fig. 1 Osteopontin (OPN) expression according to histologic type. Each product of reverse transcription-polymerase chain reaction of OPN mRNA was loaded onto a 1.5% agarose gel that was stained with ethidium bromide (0.5 µg/mL). MyImager 1000 Image Analysis System was used for the quantification of each band. OPN mRNA expression of each sample was recorded as the fold increase with respect to the expression of the housekeeping GAPDH gene. CP, classic papillary type of papillary thyroid carcinoma; FV, follicular variant of papillary thyroid carcinoma; FA, follicular adenoma.

  • Fig. 2 Sequence chromatograms of BRAF exon 15 wild-type and mutant type of PTC BRAF mutation-positive sample (mutant type) shows the heterogeneous thymine-to-adenine transversion at nucleotide position 1796, which results in a valine-to-glutamate substitution at residue 599. All of the detected BRAF mutations in this study were these BRAFV599E mutations.


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