{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:32:31Z","timestamp":1774686751414,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T00:00:00Z","timestamp":1354060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Activating mutations in the valine\u2010to\u2010glutamic acid substitution at position 600 of the v\u2010raf murine sarcoma viral oncogene homolog B1 (<jats:italic>BRAF\u20101<\/jats:italic>) gene are detected frequently in patients with papillary thyroid carcinoma (PTC). These mutations have been identified in approximately 29% to 69% of PTCs and in &gt;80% of PTCs of the tall cell variant, whereas they have not been detected in benign lesions or in the majority of those (80%) with the follicular variant of PTC. The objective of the current study was to evaluate the role of liquid\u2010based cytology (LBC) for the detection of <jats:italic>BRAF<\/jats:italic> mutations in the outcome of patients who have thyroid PTC measuring \u22641 cm and, hence, in guiding their clinical and surgical management.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>From October 2010 through June 2011, 230 consecutive cases were diagnosed as positive for malignancy on fine\u2010needle aspiration cytology processed by LBC. Of these, 73 PTCs \u22641 cm underwent <jats:italic>BRAF<\/jats:italic> mutational analysis. The aspirated material was processed using an LBC technique. After DNA extraction of the residual material, <jats:italic>BRAF<\/jats:italic> mutation analysis was performed using a direct sequencing method.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Fifty of 73 patients (68.5%) underwent surgery, and 34 of those patients (68%) had tumors that expressed a <jats:italic>BRAF<\/jats:italic> mutation (31 PTCs, including 11 tall cell variants and 3 follicular\u2010variant PTCs). A significant association between <jats:italic>BRAF<\/jats:italic> mutation and bilaterality of cancer was observed (odds ratio, 0.077; <jats:italic>P<\/jats:italic> = .0007). <jats:italic>BRAF<\/jats:italic> mutation was associated significantly with lymph node involvement (odds ratio, 19; <jats:italic>P<\/jats:italic> = .0007) but not with extracapsular infiltration (odds ratio, 0.298; <jats:italic>P<\/jats:italic> = .179).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The current results indicated that <jats:italic>BRAF<\/jats:italic> gene mutations can be identified successfully on LBC material and using other cytologic methods with high reproducibility, feasibility, and informative results. The presence of a <jats:italic>BRAF<\/jats:italic> mutation may preoperatively predict the behavior of microscopic PTC, suggesting a more aggressive surgical approach. Cancer (Cancer Cytopathol) 2013;121:291\u20137. \u00a9 2012 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21258","type":"journal-article","created":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T20:53:11Z","timestamp":1354135991000},"page":"291-297","source":"Crossref","is-referenced-by-count":100,"title":["<i>BRAF<\/i> (V600E) mutation analysis on liquid\u2010based cytology\u2010processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma"],"prefix":"10.1002","volume":"121","author":[{"given":"Esther Diana","family":"Rossi","sequence":"first","affiliation":[{"name":"Division of Anatomic Pathology and Histology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Martini","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology and Histology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Capodimonti","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology and Histology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celestino Pio","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Division of Endocrine Surgery Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio Gaetano","family":"Vellone","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology and Histology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian Franco","family":"Zannoni","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology and Histology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi Maria","family":"Larocca","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology and Histology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Fadda","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology and Histology Agostino Gemelli School of Medicine Catholic University of the Sacred Heart Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,11,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2303.2009.00659.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21026"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0956-5507.2003.00098.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.10391"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2303.2000.00228.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.9027"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000325890"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0240"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0247"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206706"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.5.7504"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-010-0729-4"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22218"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-004-1018-0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.01.010"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0607"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0896"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-87666-5"},{"key":"e_1_2_7_20_1","first-page":"405","article-title":"SIAPEC\u2010IAP Italian Consensus Working Group. 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