腺样囊性癌嗜神经侵袭的临床病理研究

目的:探讨腺样囊性癌嗜神经侵袭的临床及组织病理学特征。方法:34例经病理确诊的腺样囊性癌病例,病理切片取材见神经断面。对34例病例的临床表现、病理学特征、诊断、治疗以及预后进行分析。结果:ACC复发率似与神经侵袭的病理及临床症状、体征表现有一定关系。但本组病例样本较少,尚需更多样本进行研究。结论:对腺样囊性癌嗜神经侵袭的临床病理特征进行研究,可为其机理研究提供参考,以便早发现、早治疗,提高治愈率及生存率。     

口腔颌面部腺样囊性癌嗜神经侵袭的临床分析

目的:探讨口腔颌面部腺样囊性癌（ACC）嗜神经侵袭（PNI）发生情况及相关影响因素。方法:回顾性分析2008年1月至2016年12月山西省肿瘤医院收治的55例口腔颌面部ACC患者的临床资料,采用多元logistic回归模型分析患者临床特征与PNI发生的相关性。结果:55例患者中发生PNI 25例（45.5%）,其中腮腺...     

涎腺腺样囊性癌生物学特性研究

由上海第二医科大学附属第九人民医院口腔颌面外科研究完成的“诞腺腺样囊性癌生物学特性研究”课题，于1996年10月通过上海市科学技术成果鉴定。该研究由何荣根、邱蔚六等教授针对涎腺癌的临床和病理实践中提出的和当前国内外争论的热点课题，以腺样囊性癌（ACC）为代表，从其生物学特性认识入手进行了较系统的实验研究。分别建立了来自腭部小涎腺和腮腺的涎腺腺样囊性癌ACC-2和ACC-3细胞系，完成了各种细胞生物学特性检测和鉴定。首次证实ACC细胞在试管内能分泌基底膜成份层粘蛋白（LN）、Ⅳ型胶原、肝硫酸乙酰糖蛋白、内粘蛋白（En…     

嗜神经侵袭阳性鼻腔副鼻窦腺样囊性癌的治疗及预后分析

目的分析嗜神经侵袭(PNI)阳性鼻腔副鼻窦腺样囊性癌(ACC)的疗效, 探讨PNI在鼻腔副鼻窦ACC中的预后价值。方法回顾性分析2000年1月至2016年12月中国医学科学院肿瘤医院收治的105例鼻腔副鼻窦ACC患者的临床资料。按照美国癌症联合委员会和国际抗癌联盟第8版分期系统重新分期。随访获取患者治疗失败和生存资料, 预后影响因素的单因素分析采用Log rank检验, 多因素分析采用Cox回归比例风险模型。结果上颌窦(59例)为最常见的肿瘤原发部位, 其次为鼻腔(38例)。Ⅲ～Ⅳ期患者93例。治疗方式包括单纯手术14例, 单纯放疗13例, 术前放疗+手术10例, 手术+术后放疗68例。中位随访91.8个月, 5年局部控制率、无远处转移生存率、无进展生存率和总生存率分别为72.6%、73.0%、52.9%和78.0%。33例(31.4%)患者PNI阳性, 其5年无远处转移生存率、无进展生存率和总生存率分别为53.7%、29.4%和56.5%, 均低于PNI阴性组(分别为80.8%、63.0%和86.8%, 均P<0.05), 而两组的局部控制率差异无统计学意义(64.5%和76....     

神经细胞黏附分子49例涎腺腺样囊性癌表达及临床意义

[目的]探讨神经细胞黏附分子（NCAM）在涎腺腺样囊性癌（SACC）中的表达及临床意义。[方法]应用免疫组织化学方法检测49例涎腺腺样囊性癌中NCAM的表达情况。[结果]NCAM阳性表达率为57.14%（28/49）。NCAM在涎腺腺样囊性癌的表达与患者性别、肿瘤部位、原发灶分期无相关性。NCAM阳性表达率在管状型与实性型有显著性差异（χ^2=4.07,P=0.04）。有无神经侵犯NCAM阳性表达存在显著性差异（χ^2=10.02,P〈0.05）。[结论]神经细胞黏附分子与涎腺腺样囊性癌的神经侵袭性显著相关,NCAM在SACC中起到了重要作用。     

酪氨酸激酶B在涎腺腺样囊性癌中的表达及与嗜神经侵袭的关系

目的检测酪氨酸激酶B(TrkB)在涎腺腺样囊性癌(ACC)的表达情况，探讨TrkB与ACC嗜神经侵袭的关系。方法研究对象为28例ACC，3例正常腮腺，3例正常颌下腺，3例正常舌下腺及5例涎腺腺泡细胞癌标本，采用免疫组织化学及图像分析法对组织切片中的TrkB进行检测。结果以病理学表现为标准，28例ACC中的嗜神经侵袭率为46．4％(13／28)，TrkB阳性率为92．8％(26／28)，存在嗜神经现象组中TrkB表达水平明显高于未见嗜神经现象组(P=0．001)。TrkB的表达在正常大涎腺的导管细胞为阳性，而在腺泡细胞癌胞浆内均为阴性。结论TrkB可能作为ACC嗜神经侵袭的生物学标志物。TrkB表达的增高可能是ACC嗜神经侵袭的机理之一。     

涎腺腺样囊性癌的治疗体会

作者根据临床经验和文献复习，对涎腺腺样囊性癌的治疗提出以下体会。认为①应当废除那种把腺样囊性癌当作低度恶性处理的老观念，应有足够手术切除；②应当根据不同的原发部位特点，制订不同手术原则；③术后常规放射治疗是需要的；④术前严禁作切开活检，采用术前细针穿活检或术中冰冻切片病理检查；适当病例可采用术后化疗。     

腺样囊性癌两个细胞系体外侵袭能力比较

目的：研究转移潜能不同的两个腺样囊性癌细胞系体外侵袭能力的差异。方法：选用肺低转移细胞系Ａｃｃ－２和从中筛选出肺高转移细胞系Ａｃｃ－Ｍ,利用ＭＴＴ法检测与几种基底膜成分的粘附能力;划痕法检测运动能力;ＰＡＧＥ底物酶谱法检测分泌Ⅳ型胶原酶的能力;改良勃顿小室法观察对重组基底膜的侵袭能力。结果：①１小时后Ａｃｃ－２细胞系对３种细胞外基质的粘附率分别是纤维粘连蛋白（ＦＮ）６１．８％、层粘连蛋白（ＬＮ）４     

涎腺腺样囊性癌的复发转移因素分析

通过６０例涎腺腺样囊性癌的随诊，结果发现：局部复发率为２１．７％。复发主要与原发部位、病理类型、局部扩散及切除范围有关。腺样囊性癌局部侵袭性强，切除范围不易确定，对术后切缘有癌残留者，应追加术后放疗。本组淋巴结转移少见（３％），转移部位多在原发灶周围。在广泛切除原发灶后，一般无需行预防性颈清扫术。血行转移较多见（２１．７％），常发生于肺部。但出现血行转移的病人经治疗后仍可长期带瘤生存，故血行转移并非切除原发灶的手术禁忌证。     

茶多酚对腺样囊性癌侵袭和转移影响的体外实验研究

[目的]探讨绿茶多酚（GTP）对人腺样囊性癌（SACC）侵袭和转移的影响及其机制。[方法]不同浓度GTP处理SACC高转移细胞株ACC-M,通过Boyden小室模型测定其侵袭及黏附能力，细胞迁移实验测定细胞运动能力，流式细胞仪测定SACC细胞TGF-β1、MMP2、TIMP2表达的改变。[结果]形态学上GTP处理组细胞形态较规则、异形性小。GTP能明显抑制ACC-M细胞侵袭、黏附及运动能力（P〈0．05），并随浓度提高作用增强。GTP处理组TGF-β1表达降低（P＜0．05），MMP2阳性表达细胞减少（P〈0．05），TIMP2阳性表达细胞增多（P〈0．05），MMP2／TIMP2比值下降。[结论]GTP能抑制SACC侵袭与转移，其机制可能与直接抑制细胞迁移运动，抑制细胞基质溶解相关基因蛋白酶及转化生长因子表达有关。     

CDH12 promotes the invasion of salivary adenoid cystic carcinoma

Cadherins are found in almost all living organisms. In addition to their role in the formation and maintenance of normal tissue architecture, cadherins seem to play a crucial role in the cell-cell interactions of cancer cells in tumorigenesis, invasion and metastasis. The aim of the present study was to identify the role of CDH12 in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). Real-time PCR results showed that CDH12 is abnormally expressed in the highly metastatic SACC cell line ACC-M, compared to ACC-2, a SACC cell line with low metastatic ability. CDH12 expression was significantly higher in clinical samples with metastasis and recurrence than in those without metastasis and recurrence (P<0.05), as demonstrated by immunohistochemical analysis. Overexpression of the CDH12 protein in ACC-M cells infected with an adenovirus vector containing CDH12 enhanced the invasive and migratory ability of ACC-M cells in?vitro compared to ACC-M cells infected with empty vector. Likewise, knockdown of CDH12 by small interfering RNA efficiently inhibited the invasion and migration of ACC-M cells in?vitro. These results indicate that CDH12 may play an important role in the invasion and metastasis of SACC.     

EMMPRIN contributes to the in vitro invasion of human salivary adenoid cystic carcinoma cells

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in tumor invasion by stimulating matrix metalloproteinase (MMP) expression. Our previous immunohistochemical study found that the expression of EMMPRIN in salivary adenoid cystic carcinoma (SACC) was positively correlated with tumor perineural and perivascular invasion. The present study was designed to further investigate the role of EMMPRIN in the invasion of SACC. Western blot results showed that EMMPRIN was upregulated in the highly metastatic SACC cell line SACC-LM, compared to SACC-83, a SACC cell line with low metastatic ability. Blocking of EMMPRIN by its antibody significantly decreased the adhesion, secretion of MMP-2 and MMP-9, and invasion activity of SACC-LM cells in vitro (P<0.01). Co-cultures of SACC-LM cells with fibroblasts significantly produced elevated levels of MMP-2 and MMP-9, and promoted the in vitro invasion activity of SACC-LM cells, compared with cultures of SACC-LM cells alone (P<0.01). These results indicate that EMMPRIN may play an important role in the invasion of SACC by stimulating the expression of MMP-2 and MMP-9 in tumor and stromal cells.     

Expression of neural cell adhesion molecule in salivary adenoid cystic carcinoma and its correlation with perineural invasion

The expression of neural cell adhesion molecule (NCAM) was analyzed in immunohistochemical preparations from adenoid cystic carcinoma. The goal was to evaluate whether NCAM expression could be used as a biological marker for the perineural invasion of adenoid cystic carcinoma in the head and neck. The presence of perineural invasion and NCAM expression was evaluated in samples from 49 patients. Perineural invasion was identified in 33 of them (67%). A high incidence of perineural invasion was found in adenoid cystic carcinoma in the parotid, hard palate, maxillary sinus and oral cavity. Positive NCAM staining was observed in 28 of 49 patients (57%). Of the 28 patients with NCAM staining, perineural invasion was identified in 24 (86%). In contrast, only 9 (43%) of the 21 tumors without NCAM staining had perineural invasion. The difference in NCAM expression between cases with and without perineural invasion was statistically significant (p<0.01). When positive NCAM staining was used to estimate the presence of perineural invasion, the sensitivity was 73 and the specificity 75%. Histopathologic nodal involvement was found in 6 of 18 cases in which neck dissection had been performed. All 6 cases displayed positive NCAM staining, and 5 displayed perineural invasion in the primary adenoid cystic carcinoma. In conclusion, NCAM expression can, to a certain extent, be used as a predictor of perineural invasion in adenoid cystic carcinoma. Moreover, lymph node metastases could serve as a clinical indicator for perineural invasion and for NCAM expression.     

Inhibition of STAT3 reduces proliferation and invasion in salivary gland adenoid cystic carcinoma

In this study, we accessed the expression and correlation of p-STAT3 with Survivin, Cyclin D1, CD147, Slug and Ki67 by immunohistochemical staining of human tissue microarray which contains 72 adenoid cystic carcinoma (AdCC), 12 pleomorphic adenoma (PMA) and 18 normal salivary gland (NSG) using digital pathological scanner and scoring system. We found that the expression of p-STAT3, Survivin, Slug, Cyclin D1 and CD147 was significantly increased in AdCC as compared with PMA and (or) NSG (p<0.05). While, the level of p-STAT3 and expression of Cyclin D1 and CD147 was not associated with pathological type of human AdCC (p>0.05). Correlation analysis of these proteins revealed that p-STAT3 up-regulates the expression of Survivin, Slug, Cyclin D1 and CD147 (p<0.05). Moreover, the activation of STAT3 was associated with proliferation marker Ki-67 (p<0.05). Selective inhibition of STAT3 by a small molecule S3I-201 significantly reduced human SACC-83 and SACC-LM cells proliferation, migration and invasion with the corresponding decrease in expression of Survivin, Slug, Cyclin D1 and CD147. These findings indicate that high phosphorylation level of STAT3 in AdCC is related to Survivin, Slug, Cyclin D1 and CD147. We suggest that the inhibition of STAT3 may be a novel strategy for neoadjuvant chemotherapeutic treatment of AdCC.     

EMMPRIN silencing inhibits proliferation and perineural invasion of human salivary adenoid cystic carcinoma cells in vitro and in vivo

Salivary adenoid cystic carcinoma (SACC) is a frequent subtype of salivary gland malignancy, and it has an important biological behavior for perineural invasion (PNI). Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in the invasive property of many malignancies by stimulating matrix metalloproteinase (MMP) expression. The present study was designed to investigate the role and possible mechanism of EMMPRIN in the PNI of SACC using RNA interference (RNAi) technology. We found that silencing of EMMPRIN expression in the human SACC cell line (SACC-83) suppressed the cell proliferation, adhesion, MMP-2 and MMP-9 secretion, and PNI activity in vitro. EMMPRIN silencing also inhibited the tumor growth and Ki-67 labeled proliferation index in vivo. Using tumor PNI models in nude mice, EMMPRIN silencing inhibited the infiltration, swelling and functional loss of the affected sciatic nerves, as well as the expression of MMP-2 and MMP-9. These results demonstrate that EMMPRIN participates in the PNI of SACC cells by mediating the expression of MMP-2 and MMP-9. Our findings suggest that EMMPRIN is a potential target for anti-PNI treatment in SACC.     

Ezrin在涎腺腺样囊性癌组织中的表达

目的:探讨Ezrin在涎腺腺样囊性癌组织中的表达及意义。方法:用免疫组织化学SP法检测Ezrin在涎腺腺样囊性癌组织和正常涎腺组织中的表达,分析其在涎腺腺样囊性癌组织中的表达与肿瘤的侵袭性、复发、转移和预后的关系。结果:Ezrin在涎腺腺样囊性癌和正常涎腺组织中的阳性率表达分别为44.68%和9.09%,P<0.05;在癌细胞中主要为胞质内表达,染色深,而在正常涎腺组织则主要为细胞膜表达,染色浅或阴性。Ezrin的表达强度与有无神经受侵、有无发生局部复发及远处转移相关,P<0.05。Ezrin表达阳性组和阴性组的5年累积生存率分别为66.70%和100.00%,10年累及生存率分别为27.83%和95.00%,阳性组较阴性组预后差,P<0.05。结论:Ezrin的表达强度与涎腺腺样囊性癌的发生、侵袭性、复发和转移性有关,且Ezrin阳性表达预示患者预后不良。