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犬黑色素瘤诊断:RACK1作为一种潜在的生物标志物

Canine melanoma diagnosis: RACK1 as a potential biological marker.

作者信息

Campagne C, Julé S, Alleaume C, Bernex F, Ezagal J, Château-Joubert S, Estrada M, Aubin-Houzelstein G, Panthier J-J, Egidy G

机构信息

INRA, UMR955 de Génétique fonctionnelle et médicale, Ecole Nationale Vétérinaire d'Alfort, 7 avenue du Général de Gaulle, Maisons-Alfort, F-94704 France. Email:

出版信息

Vet Pathol. 2013 Nov;50(6):1083-90. doi: 10.1177/0300985813490754. Epub 2013 Jun 4.

Abstract

Melanoma diagnosis in dogs can be challenging due to the variety of histological appearances of canine melanocytic neoplasms. Markers of malignancy are needed. Receptor for activated C-kinase 1 (RACK1) was found to characterize melanomas in other mammals. We investigated the value of RACK1 detection in the classification of 19 cutaneous and 5 mucosal melanocytic neoplasms in dogs. These tumors were categorized as melanocytomas or benign and melanomas or malignant after evaluation of their morphology, mitotic index, and Ki-67 growth fraction. Using immunofluorescence, we confirmed microphthalmia-associated transcription factor (MITF) as a marker of normal and transformed melanocytic cells in dog tissues. All control (n = 10) and tumoral (n = 24) samples stained positively for MITF (34/34, 100%). Whereas RACK1 was not detected in healthy skin melanocytes, melanocytic lesions were all positive for RACK1 signal (24/24, 100%). RACK1 cytoplasmic staining appeared with 2 distinct distribution patterns: strong, diffuse, and homogeneous or granular and heterogeneous. All melanoma samples (13/13, 100%) stained homogeneously for RACK1. All melanocytomas (11/11, 100%) stained heterogeneously for RACK1. Immunohistochemistry was less consistent than immunofluorescence for all labelings in melanocytic lesions, which were often very pigmented. Thus, the fluorescent RACK1-MITF labeling pattern helped to distinguish melanomas from melanocytomas. Furthermore, RACK1 labeling correlated with 2 of 11 morphological features linked to malignancy: cell and nuclear size. These results suggest that RACK1 may be used as a marker in dog melanomas.

摘要

由于犬黑素细胞肿瘤的组织学表现多样,犬黑色素瘤的诊断可能具有挑战性。因此需要恶性肿瘤的标志物。已发现活化C激酶1受体(RACK1)可作为其他哺乳动物黑色素瘤的特征。我们研究了RACK1检测在犬19例皮肤和5例黏膜黑素细胞肿瘤分类中的价值。在评估这些肿瘤的形态、有丝分裂指数和Ki-67生长分数后,将其分类为黑素细胞瘤或良性肿瘤以及黑色素瘤或恶性肿瘤。通过免疫荧光,我们证实小眼畸形相关转录因子(MITF)是犬组织中正常和转化黑素细胞的标志物。所有对照样本(n = 10)和肿瘤样本(n = 24)的MITF染色均为阳性(34/34,100%)。而在健康皮肤黑素细胞中未检测到RACK1,黑素细胞病变的RACK1信号均为阳性(24/24,100%)。RACK1的细胞质染色呈现两种不同的分布模式:强、弥漫且均匀或颗粒状且不均匀。所有黑色素瘤样本(13/13,100%)的RACK1染色均为均匀。所有黑素细胞瘤(11/11,100%)的RACK1染色均为不均匀。对于黑素细胞病变中所有标记物的检测,免疫组织化学的一致性不如免疫荧光,因为这些病变通常色素沉着很深。因此,荧光RACK1-MITF标记模式有助于区分黑色素瘤和黑素细胞瘤。此外,RACK1标记与11种与恶性相关的形态学特征中的2种相关:细胞和细胞核大小。这些结果表明,RACK1可作为犬黑色素瘤的标志物。

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