Jour G, West K, Ghali V, Shank D, Ephrem G, Wenig B M
Department of Pathology and Laboratory Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY 10003, USA.
Head Neck Pathol. 2013 Sep;7(3):224-31. doi: 10.1007/s12105-012-0417-9. Epub 2013 Jan 13.
Salivary gland tumors (SGT) are a heterogeneous group of lesions. There is conflicting data concerning the molecular events involving the tumour suppressor retinoblastoma protein (pRb) pathway in these tumors. Few studies examined the alterations in components of the Rb pathway by immunohistochemical (IHC) methods in benign and malignant SGTs. Furthermore, recent evidence implicates human papillomavirus (HPV) in mucoepidermoid carcinoma (MEC) carcinogenesis. The purpose of our study is to examine p16(INK4A) and cyclin D1 expression in a variety of benign and malignant salivary gland tumors, and to investigate p16(INK4A) expression as a surrogate marker for HPV infection in MEC. Our series includes 30 malignant tumors [14 MEC, 6 acinic cell carcinomas (ACC), 5 polymorphous low grade adenocarcinomas (PLGA), 5 (AdCC)] and 14 benign tumors (4 benign cysts, 5 Warthin tumors and 5 pleomorphic adenomas (PA). All cases were tested by IHC for p16(INK4A) and cyclin D1. Testing for HPV wide spectrum (HPV-WS) was performed by in situ hybridization in all MEC cases. Staining intensity was recorded semi quantitatively (on a scale from 0 to 4+). Fisher's exact test and Pearson X2 test with a p < 0.05 were used. Cyclin D1 and p16(INK4A) are expressed similarly in malignant and benign tumors (p = 0.146 and p = 0.543, respectively). None of the MEC cases showed nuclear reactivity for HPV-WS. Statistical analysis showed positive correlation between cyclin D1 and p16(INK4A) expression. Our findings suggest that p16(INK4A) overexpression is likely secondary to cyclin D1 gene upregulation or amplification. Further molecular studies are warranted.
涎腺肿瘤（SGT）是一组异质性病变。关于这些肿瘤中涉及肿瘤抑制蛋白视网膜母细胞瘤蛋白（pRb）通路的分子事件，存在相互矛盾的数据。很少有研究通过免疫组织化学（IHC）方法检测良性和恶性SGT中Rb通路成分的改变。此外，最近有证据表明人乳头瘤病毒（HPV）与黏液表皮样癌（MEC）的致癌作用有关。我们研究的目的是检测多种良性和恶性涎腺肿瘤中p16（INK4A）和细胞周期蛋白D1的表达，并研究p16（INK4A）表达作为MEC中HPV感染替代标志物的情况。我们的系列研究包括30例恶性肿瘤[14例MEC、6例腺泡细胞癌（ACC）、5例多形性低度腺癌（PLGA）、5例腺样囊性癌（AdCC）]和14例良性肿瘤（4例良性囊肿、5例沃辛瘤和5例多形性腺瘤（PA））。所有病例均通过IHC检测p16（INK4A）和细胞周期蛋白D1。所有MEC病例均通过原位杂交进行广谱HPV（HPV-WS）检测。染色强度采用半定量记录（范围为0至4+）。采用Fisher精确检验和p<0.05的Pearson X2检验。细胞周期蛋白D1和p16（INK4A）在恶性和良性肿瘤中的表达相似（分别为p=0.146和p=0.543）。所有MEC病例均未显示HPV-WS的核反应性。统计分析显示细胞周期蛋白D1与p16（INK4A）表达之间呈正相关。我们的研究结果表明，p16（INK4A）过表达可能继发于细胞周期蛋白D1基因的上调或扩增。有必要进行进一步的分子研究。
