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。     

人涎腺腺样囊性癌嗜神经侵袭超微结构的观察研究

目的:通过电镜检测来进一步探索人涎腺腺样囊性癌嗜神经侵袭的超微形态特征.方法:将人涎腺腺样囊性癌Acc-M细胞系注射入5只裸鼠双侧臀部肌肉内,切取其中发生神经侵袭并出现功能障碍的荷瘤;通过透射电镜检测来观察腺样囊性癌的嗜神经侵袭过程. 结果:肿瘤细胞破坏神经外膜及神经束膜,进入神经纤维之间,并以吞噬的方式对神经纤维进行侵袭,致使髓鞘、轴突发生变性、溶解而被吸收.结论:涎腺腺样囊性癌细胞在对神经的侵袭过程中具有一定的吞噬作用,且这种现象在神经侵袭中起了很重要的作用.     

腺样囊性癌组织神经生长因子及受体表达与神经浸润相关性的探讨

目的:观察神经生长因子(NGF)及其功能性受体酪氨酸激酶A(TrkA)在腺样囊性癌(ACC)的表达情况,探讨NGF和TrkA在ACC神经浸润(NI)过程中的作用及其意义。方法:47例石蜡包埋ACC标本,常规HE染色,观察有无NI;并依据形态特点将NI类型分为侵入型和围神经型。免疫组织化学检测NGF和TrkA的表达情况。7例新鲜ACC标本,RT-PCR法检测NGF和TrkA的mRNA的表达水平。结果:47例ACC中37例存在NI,其中侵入型25例、围神经型12例。7例新鲜标本5例存在NI。免疫组织化学染色结果显示,NGF在NI组阳性率为86.49%,非NI组为50.00%,侵入型组为92.00%,围神经组为90.00%;TrkA在NI组阳性率为59.46%,非NI组为40.00%,侵入型组为68.00%,围神经组为50.00%。RT-PCR检测结果显示,NGF mRNA的表达水平在NI组较高,TrkA mRNA的表达两组差异无统计学意义。结论:神经周围癌细胞NGF的表达高于远离神经的癌细胞,而其受体TrkA在神经束膜和肿瘤细胞表面均有表达,NGF与其受体的结合促进癌细胞向着神经聚集并沿其生长,形成NI。     

酪氨酸激酶B在涎腺腺样囊性癌中的表达及意义

目的探讨酪氨酸激酶B（TrkB）与涎腺腺样囊性癌（SACC）的关系。方法采用免疫组化链亲和素法分析45例SACC的TrkB表达,并统计分析TrkB与SACC病理学分型、临床分期、区域淋巴结转移和神经侵犯的关系。结果TrkB表达与SACC病理学分型无明显相关（P〉0.05）,而与临床分期、区域淋巴结转移和神经侵犯呈正相关（P〈0.05）。结论TrkB能促进SACC区域淋巴结转移和神经侵犯的发生,并可作为指标来预测SACC的区域淋巴结转移和神经侵犯。     

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...     

Neural cell adhesion molecule and perineural invasion in gallbladder cancer

To clarify the role of neural cell adhesion molecule (NCAM) in perineural invasion, NCAM expression was studied by immunohistochemical staining in 26 cases with gallbladder cancer. In gallbladder cancer, the incidence of perineural invasion and that of positive NCAM expression was 42% and 31%, respectively, which are less frequent than those of bile duct cancer in our previous report. Perineural invasion was observed in 88% of the patients with positive expression of NCAM and in 22% of those with negative expression. The former is similar to that of bile duct cancer but the latter is significantly lower. Eighty percent of the cancer cells that invaded the perineural space were positive for NCAM, when the primary tumor was positive for NCAM expression. Therefore, in gallbladder cancer, positive cells in NCAM expression likely invade the perineural spaces. However, the perineural invasion of negative cells in NCAM expression is not likely to occur as compared to bile duct cancer. In conclusion, perineural invasion in gallbladder cancer is not as common as in bile duct cancer, but the role of NCAM in perineural invasion is more important in gallbladder cancer than in bile duct cancer. © 1995 Wiley-Liss, Inc.     

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.     

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....     

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.     

Twist在涎腺腺样囊性癌中的表达及其临床意义

目的 探讨转录因子Twist在涎腺腺样囊性癌中的表达水平及其与各临床病理因素的关系.方法 采用免疫组化方法检测48例涎腺腺样囊性癌、18例多形性腺瘤和10正常腮腺组织中Twist蛋白的表达情况,分析Twist表达与腺样囊性癌临床病理因素的关系.结果 Twist在涎腺腺样囊性癌组织中的表达水平明显高于多形性腺瘤和正常腮腺组织(P<0.05).Twist表达与腺样囊性癌的病理分型、嗜神经侵袭、术后复发及远位转移有相关性(P<0.05).结论 Twist蛋白表达可能与涎腺腺样囊性癌的分化调节、嗜神经侵袭及远位转移有关.检测Twist的表达水平对判断腺样囊性癌患者的预后有一定的参考价值.     

Expression of epidermal growth factor receptor in different salivary adenoid cystic carcinoma cell lines

Objective： To investigate the expression of epidermal growth factor receptor, a receptor tyrosine protein kinase, in the subcellular fractions of human salivary adenoid cystic carcinoma cell lines SACC-83 and SACC-LM. Methods： Low metastatic and high metastatic cells of the adenoid cystic carcinoma, SACC-83 and SACC-LM, were cultured. Their subcellular fractions were extracted. The expression of epidermal growth factor receptor was detected with Western blot method, and the results of protein expression were quantitatively analyzed by FluorChem V2.0 software. Results： The results of Western blot analysis indicated that, EGFR expression on the membrane of SACC-83 cells was significantly higher than that of SACC-LM cells, but its expression in cytoplasm was significantly less in the former than the later （P〈0.01）. In SACC-83 cell line, EGFR was over-expressed in membrane （P〈0.01）, but in SACC-LM cell line, EGFR was over-expressed in cytoplasm （P〈0.01）. Conclusion： The results suggest that the obtaining of metastasis ability is related to the high expression of EGFR protein in cytoplasm, so the molecular targeting therapy to EGFR may be an ideal treatment for the invasion and metastasis of salivary adenoid cystic carcinoma.     

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.     

Neural cell adhesion molecule (NCAM) and perineural invasion in bile duct cancer

Perineural invasion is associated with tumor spreading and an unfavorable prognosis in a variety of cancers. Recently, neural cell adhesion molecule (NCAM) has been reported to be affinitive to neural tissues, which suggests some relationship between NCAM and perineural invasion. This study was designed to elucidate the role of the expression of NCAM on the development of perineural invasion in bile duct cancer. A histopathologic study was performed on 24 patients with bile duct carcinoma who underwent resections. The overall incidence of NCAM expression in the resected specimen was 66.7% and that of perineural invasion was 87.5%. Furthermore, NCAM expression was shown to be positive in 16 (76%) out of 21 cases in whom perineural invasion was observed. A significant positive correlation was found between the expression of NCAM and perineural invasion in bile duct cancer. These results highlight an important role of NCAM in the development of perineural invasion in bile duct cancer. © 1993 Wiley-Liss, Inc.     

The role of basement membrane proteins on the expression of neural cell adhesion molecule (N-CAM) in an adenoid cystic carcinoma cell line

We investigated the presence of neural cell adhesion molecule (N-CAM) in the adenoid cystic carcinoma cell line CAC2 using immunofluorescence microscopy. Additionally, we analysed the role of laminin and type IV collagen in N-CAM expression. We demonstrated that cultured adenoid cystic carcinoma cells express N-CAM. Control cells presented a scattered N-CAM expression on cell membrane, and type IV collagen had no effect in N-CAM distribution. CAC2 cells grown on laminin-coated coverslips expressed N-CAM concentrated on cell lamellipodia suggesting relationship with migratory activity. Our results showed that cultured adenoid cystic carcinoma cells express N-CAM and this expression is modulated by extracellular matrix.     

E钙粘素在涎腺腺样囊性癌中的表达及其意义

背景与目的:近年来关于上皮型钙粘素与肿瘤关系的研究比较多,但不同研究得到的结果差异较大,而且近年来的研究显示,E钙粘素在肿瘤转移过程中的作用可能具有多面性.本文旨在研究E钙粘素在涎腺腺样囊性癌中的表达水平,探讨E钙粘素与涎腺腺样囊性癌的神经侵犯、局部复发、远处转移以及预后的关系.方法:采用免疫组化技术检测55例涎腺腺样囊性癌组织标本和20例正常涎腺组织中E钙粘素的表达.应用Kaplan-Meier法进行生存分析,组间比较用log-rank检验,两组比率的比较采用χ2检验.结果:本组患者的5年和10年生存率分别为78.2%和51.4%:E钙粘素在正常涎腺组织中的阳性率(90.0%)显著高于涎腺腺样囊性癌组织(63.6%)(P＜0.05);E钙粘素在有神经受侵、局部复发及远处转移者的肿瘤组织中的阳性率(50.0%、52.4%及47.8%),均低于无神经受侵、无局部复发及无远处转移者(71.4%、70.6%及75.0%).结论:E钙粘素在涎腺腺样囊性癌组织中表达下调;其表达水平与神经侵犯、局部复发及发生远处转移相关.     

涎腺腺样囊性癌中丝裂原激活蛋白激酶p38的表达及意义

目的 探讨丝裂原激活蛋白激酶p38(p38MAPK)在涎腺腺样囊性癌(SACC)中的表达及临床意义.方法 采用组织微阵列平台,运用免疫组化和原位杂交技术,检测52例SACC和11例正常涎腺组织中p38MAPK蛋白和mRNA的表达,并分析其与SACC 临床病理特征的关系.结果 正常涎腺组织和SACC组织中,p38MAPK蛋白的阳性表达率分别为36.4%和96.2%,差异有统计学意义(P＜0.01).p38MAPK蛋白表达与SACC的淋巴结转移、神经侵犯有关(均P＜0.05).正常涎腺组织和SACC组织中,p38MAPK mRNA的阳性表达率分别为45.5%和94.2%,差异有统计学意义(P＜0.01).p38MAPK mRNA表达与SACC的淋巴结转移、神经侵犯有关(均P＜0.05).SACC组织中,p38MAPK蛋白与mRNA的表达呈正相关(r=0.409,P＜0.01).结论 在SACC组织中,p38MAPK表达上调,p38MAPK通路可能与SACC的发生、侵袭和转移有关.

Abstract：

Objective To investigate the expression of p38 mitogen-activated protein kinase (p38MAPK) in salivary adenoid cystic carcinoma (SACC) tissues and their clinicopathologic significance.Methods The protein and mRNA expressions of p38MAPK were examined by immunohistochemistry and in situ hybridization, respectively, in 52 cases of SACC and in 11 normal salivary gland tissues adjacent to the tumors on a tissue microarray platform.Results The positive rate of p38MAPK protein expression in the paracancerous normal salivary gland tissues and that in SACC were 36.4% and 96.2%, respectively,showing a significant statistical difference (P ＜ 0.01 ).The protein expression of p38MAPK was positively correlated with the lymph node metastasis and nerve involvement (P ＜ 0.05 ).The positive rates of p38MAPK mRNA in the paracancerous tissues and in the SACC tissues were 45.5% and 94.2%,respectively, with a significant statistical difference (P ＜0.01 ).The mRNA expression of p38MAPK was positively correlated with the lymph node metastasis and nerve involvement (P ＜ 0.05 ).In the SACC, there was a notable positive correlation between the p38MAPK protein and mRNA expressions (r = 0.409, P ＜0.01).Conclusions The expression of p38MAPK is up-regulated in salivary adenoid cystic carcinoma.p38MARK may be involved in the tumorigenesis, development and metastasis of this cancer.