BRAF Mutation Predicts a Poorer Clinical Prognosis for Papillary Thyroid Cancer

Xing, Mingzhao; Westra, William H.; Tufano, Ralph P.; Cohen, Yoram; Rosenbaum, Eli; Rhoden, Kerry J.; Carson, Kathryn A.; Vasko, Vasily; Larin, Alexander; Tallini, Giovanni; Tolaney, Sara M.; Holt, Elizabeth H.; Hui, Pei; Umbricht, Christopher B.; Basaria, Shehzad; Ewertz, Marge; Tufaro, Anthony P.; Califano, Joseph A.; Ringel, Matthew D.; Zeiger, Martha A.; Sidransky, David; Ladenson, Paul W.

doi:10.1210/jc.2005-0987

Cited by 898 publications

(805 citation statements)

References 29 publications

Supporting

Mentioning

735

Contrasting

Unclassified

Order By: Relevance

“…Additionally, the BRAF mutation occurs most commonly in aggressive subtypes of PTC [178,201]. Loss of NIS and TPO are early markers of dedifferentiation and they are also responsible for poor prognosis in BRAF positive PTCs [202].…”

Section: Molecular Targets In Histopathological Diagnosis and Classifmentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

Section: Molecular Targets In Histopathological Diagnosis and Classifmentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

“…BRAF mutations are the most common mutation in PTCs, and the transverse point mutation at codon 600 ( BRAF V600E) is the most common type of BRAF mutations 15, 16, 17. Several studies demonstrated a strong association between BRAF mutations and poor clinicopathological outcomes for patients with PTCs 18, 19, 20. RAS mutations can be found in follicular neoplasms and are more common in FTCs (40–50%) than in follicular thyroid adenomas (20–40%) 21, 22, 23, 24.…”

Section: Introductionmentioning

confidence: 99%

Genetic alterations of differentiated thyroid carcinoma in iodine‐rich and iodine‐deficient countries

et al. 2016

View full text Add to dashboard Cite

BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine‐rich country (Japan) and an iodine‐deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele‐specific polymerase chain reaction (AS‐PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS,HRAS, and KRAS), and RT‐PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E,RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine‐rich and iodine‐deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer.

show abstract

“…The additional molecular changes that promote tumor progression, however, are not well characterized, but mutations in other oncogenes and tumor suppressor genes and altered cell signaling, cell cycle regulation, and apoptosis have been described in clinicopathologically aggressive thyroid neoplasms. 16,18,[20][21][22] As these changes have not been studied in the columnar cell variant of papillary thyroid carcinoma, we screened for mutations in BRAF and evaluated the immunophenotypic expression of the neoplasia-associated biomarkers b-catenin, cyclin D1, the cell proliferation marker Ki-67 (MIB-1), bcl-2, p53, estrogen receptor (ER), and progesterone receptor (PR) in nine cases of clinically aggressive and indolent columnar cell carcinomas.…”

mentioning

confidence: 99%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

View full text Add to dashboard Cite

The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF V600E ), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasiaassociated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of b-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Keywords: BRAF (BRAF V600E ); b-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma Papillary thyroid carcinoma is a common endocrine neoplasm that is typically indolent and associated with long-term survival. This favorable biological behavior reflects the vast majority of conventional and histological variants of well-differentiated papillary thyroid carcinoma. However, a more aggressive tumoral growth characterizes a small subset that behaves more akin to poorly differentiated and undifferentiated thyroid carcinoma. Initially included in this group of aggressive neoplasms, the columnar cell variant is a rare subtype with variable biological behavior. Early reports described tumors with fast growth rates, aggressive local invasion, high rates of recurrence, early metastasis to regional lymph nodes and distant

show abstract

BRAF Mutation Predicts a Poorer Clinical Prognosis for Papillary Thyroid Cancer

Abstract: In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.

Cited by 898 publications

References 29 publications

An update on molecular biology of thyroid cancers

An update on molecular biology of thyroid cancers

Genetic alterations of differentiated thyroid carcinoma in iodine‐rich and iodine‐deficient countries

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Contact Info

Product

Resources

About