BRAF V600E associates with cytoplasmatic localization of p27kip1 and higher cytokeratin 19 expression in papillary thyroid carcinoma

被引:24
作者
Guerra, Anna [1 ]
Marotta, Vincenzo [2 ]
Deandrea, Maurilio [3 ]
Motta, Manuela [4 ]
Limone, Paolo Piero [3 ]
Caleo, Alessia [5 ]
Zeppa, Pio [1 ]
Esposito, Silvano [1 ]
Fulciniti, Franco [6 ]
Vitale, Mario [1 ]
机构
[1] Univ Salerno, Dept Med & Surg, I-84081 Salerno, Italy
[2] Univ Naples Federico II, Dept Clin & Mol Endocrinol & Oncol, I-80131 Naples, Italy
[3] AO Ordine Mauriziano, Presidio Osped Umberto 1, SC Endocrinol, Turin, Italy
[4] AO Ordine Mauriziano, Presidio Osped Umberto 1, SC Anat Patol, Turin, Italy
[5] AOU San Giovanni Dio & Ruggi Aragona, SC Anat Patol, Salerno, Italy
[6] Ist Nazl Tumori Fdn G Pascale, AF Anat Patol & Citopatol, SSD Citopatol, Naples, Italy
关键词
BRAFV600E; Thyroid cancer; CK19; Gal-3; p27Kip1; FINE-NEEDLE-ASPIRATION; KINASE INHIBITOR P27(KIP1); MESSENGER-RNA; DEPENDENT DEGRADATION; BREAST-CANCER; GALECTIN-3; P27; PROTEIN; BRAF(V600E); BENIGN;
D O I
10.1007/s12020-012-9843-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAF (V600E) mutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAF (V600E) mutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAF (V600E) (P a parts per thousand currency sign 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0-5 % of cells with nuclear staining, 6-15 % or > 15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAF (V600E) positive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent (P = 0.024). In conclusion, we provide evidences that BRAF (V600E) is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC.
引用
收藏
页码:165 / 171
页数:7
相关论文
共 46 条
[1]  
Akahani S, 1997, CANCER RES, V57, P5272
[2]   Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules [J].
Beesley, MF ;
McLaren, KM .
HISTOPATHOLOGY, 2002, 41 (03) :236-243
[3]   Breast cancer banishes p27 from nucleus [J].
Blain, SW ;
Massagué, J .
NATURE MEDICINE, 2002, 8 (10) :1076-1078
[4]   Molecular detection of thyroid cancer: an update [J].
Bojunga, J ;
Zeuzem, S .
CLINICAL ENDOCRINOLOGY, 2004, 61 (05) :523-530
[5]   Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue [J].
Brown, Lewis M. ;
Helmke, Steve M. ;
Hunsucker, Stephen W. ;
Netea-Maier, Romana T. ;
Chiang, Simon A. ;
Heinz, David E. ;
Shroyer, Kenneth R. ;
Duncan, Mark W. ;
Haugen, Bryan R. .
MOLECULAR CARCINOGENESIS, 2006, 45 (08) :613-626
[6]   Decreased levels of the cell-cycle inhibitor p27(Kip1) protein: Prognostic implications in primary breast cancer [J].
Catzavelos, C ;
Bhatacharya, N ;
Ung, YC ;
Wilson, JA ;
Roncari, L ;
Sandhu, C ;
Shaw, P ;
Yeger, H ;
MoravaProtzner, I ;
Kapusta, L ;
Franssen, E ;
Pritchard, KI ;
Slingerland, JM .
NATURE MEDICINE, 1997, 3 (02) :227-230
[7]   Immunohistochemical diagnosis of papillary thyroid carcinoma [J].
Cheung, CC ;
Ezzat, S ;
Freeman, JL ;
Rosen, IB ;
Asa, SL .
MODERN PATHOLOGY, 2001, 14 (04) :338-342
[8]  
CHIARIOTTI L, 1992, ONCOGENE, V7, P2507
[9]   Unusual Short-Term Complete Response to Two Regimens of Cytotoxic Chemotherapy in a Patient with Poorly Differentiated Thyroid Carcinoma [J].
Crouzeix, Genevieve ;
Michels, Jean-Jacques ;
Sevin, Emmanuel ;
Aide, Nicolas ;
Vaur, Dominique ;
Bardet, Stephane .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (09) :3046-3050
[10]   IDENTIFICATION OF GALECTIN-3 AS A FACTOR IN PRE-MESSENGER-RNA SPLICING [J].
DAGHER, SF ;
WANG, JL ;
PATTERSON, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (04) :1213-1217