生物治疗涎腺腺样囊性癌的研究进展

涎腺腺样囊性癌是目前最为常见的涎腺恶性肿瘤之一,该肿瘤具有显著的两大生物学特性：嗜神经侵袭性和肺高转移性,而这两大生物学特性也直接影响着涎腺腺样囊性癌的治疗和预后.该肿瘤对手术、放射治疗及化学药物治疗效果均不十分理想,因此,生物治疗引起了国内外学者的广泛关注研究,并取得了一定的成果.     

涎腺基底细胞腺瘤和腺癌与腺样囊性癌的比较观察

目的 研究涎腺基底细胞腺瘤和基底细胞腺癌与腺样囊性癌的形态学特征、免疫表型和鉴别诊断。方法 对5例基底细胞腺瘤，5例基底细胞腺癌和7例腺样囊性癌进行了免疫组化和双重免疫电镜(2例)的观察。结果 基底细胞腺瘤和基底细胞腺癌在免疫表型方面非常相似；基底细胞腺瘤(癌)与腺样囊性癌之间在免疫表型和超微结构方面有一定的差别。结论 基底细胞腺瘤和基底细胞腺癌的鉴别诊断基于两者的生长方式和组织学特征。免疫组化和免疫电镜观察有助于基底细胞腺瘤(癌)与腺样囊性癌的鉴别诊断。     

乳腺腺样囊性癌与涎腺腺样囊性癌的临床病理分析及比较

目的 分析比较乳腺腺样囊性癌(adenoid cystic carcinoma of the breast,BAdCC)和涎腺腺样囊性癌(salivary glands adenoid cystic carcinoma,SGAdCC)的临床特点、组织形态、免疫表型、生物学行为及预后的异同点.方法 收集8例BAdCC和12例SGAdCC的临床资料,行光镜观察及免疫组化染色,对两组病例进行生存分析.结果 BAdCC患者平均年龄51岁,临床常表现为缓慢的膨胀性生长的肿块,偶伴有疼痛,神经周围浸润不明显,所有病例计56枚淋巴结均未见转移,1例在术后5年复发;SGAdCC患者平均年龄53.5岁,半数患者出现疼痛和麻木,神经周围及邻近骨胳常浸润常见,27枚淋巴结有5枚转移(18.5%),术后短期复发常见,二者的无复发生存率差异有显著性.结论 BAdCC非常罕见,BAdCC与SGAdCC在组织形态和免疫表型上无明显的差异,但二者的生物学行为明显不同,BAdCC呈惰性临床过程,而SGAdCC具有明显的侵袭性,导致这种差异的原因需进一步研究.     

趋化因子 SDF-1α及其受体介导涎腺腺样囊性癌细胞的趋化与侵袭

探讨趋化因子SDF-1α及其受体CXCR4对涎腺腺样囊性癌细胞趋化与侵袭活性的促进作用。采用RT-PCR法检测涎腺腺样囊性癌肺高、低转移细胞株ACC-M和ACC-2中CXCR4 mRNA的表达;Boyden趋化小室法检测在SDF-1α作用下ACC-M细胞和ACC-2细胞的趋化与侵袭活性;检测CXCR4 mAb对ACC-M细胞和ACC-2细胞趋化活性和侵袭活性的抑制作用。结果显示:2株涎腺腺样囊性癌细胞中均存在不同程度CXCR4 mRNA的表达,其在肺高转移细胞株ACC-M中的表达显著高于肺低转移细胞株ACC-2;SDF-1α对2种细胞均具有趋化活性和侵袭活性,且对ACC-M细胞的趋化活性和侵袭活性显著强于ACC-2细胞;CXCR4 mAb能够抑制涎腺腺样囊性癌细胞的这种趋化活性和侵袭活性。趋化因子SDF-1α及其受体CXCR4能够介导涎腺腺样囊性癌细胞的趋化与侵袭。     

涎腺腺样囊性癌和基底细胞腺瘤的免疫表型及临床病理特征

目的观察CK7、Calponin、CD117、Ki-67在涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)和基底细胞腺瘤(basal celladenoma,BCA)中的免疫表型及其病理组织形态学差异,以提高对该类肿瘤鉴别诊断的认识。方法对发生于涎腺的26例BCA和17例ACC进行临床和病理组织形态观察并免疫组化标记(CK7、Calponin、CD117、Ki-67)。结果临床特点为两种肿瘤的发病年龄相似,但发生部位不同,ACC好发于腮腺以外的小涎腺,BCA多数发生于腮腺;病理特点为前者表现为浸润性生长并累及周围组织;免疫组化显示两种肿瘤存在免疫表型差异:其中CD117在ACC和BCA之间的强阳性率差异有统计学意义(P<0.05);Ki-67在BCA和ACC之间的强阳性率差异有统计学意义(P<0.01)。结论 ACC具有浸润性生长的生物学特征,病理特点上与BCA鉴别主要基于两者的生长方式和组织形态学检查,CD117和Ki-67免疫组化标记有助于其鉴别诊断。     

整合素连接激酶与磷酸脂酶在人涎腺腺样囊性癌中的表达

目的观察整合素连接激酶(ILK)与磷酸酶基因(PTEN)在涎腺腺样囊性癌(SACC)中的表达,探讨ILK,PTEN在SACC发生发展中的作用。方法通过免疫组化法检测25例SACC标本及12例正常涎腺标本中ILK,PTEN在SACC中的表达。结果ILK在SACC细胞中高表达并定位在细胞浆,在正常涎腺组织中无表达或低表达(P0.05),PTEN在SACC细胞中低表达,在正常涎腺组织中高表达(P0.05)。结论ILK和PTEN在SACC的不同表达预示二者的功能不同。     

涎腺腺样囊性癌中ADAM-17的表达及临床意义

目的探讨ADAM-17在涎腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)中的表达及临床意义。方法收集48例SACC石蜡组织和20例新鲜组织,分别采用免疫组化EnVision两步法和RT-PCR法检测SACC组织中ADAM-17蛋白和mRNA表达水平,并分析其与临床病理学参数之间的相关性。结果 ADAM-17蛋白在48例SACC组织中阳性率为72.9%(35/48),ADAM-17mRNA水平在20例SACC中平均相对表达量为(0.40±0.18),两者的表达均高于正常对照组,差异具有统计学意义(P<0.001),两者的表达与肿瘤的大小、TNM分期和患者的生存时间均有相关性。结论 ADAM-17在SACC中高表达,可能介导癌组织生长、侵袭和转移,其有望成为一个新的治疗靶点。     

细针吸取细胞块技术在涎腺腺样囊性癌诊断中的应用

<正>涏腺腺样囊性癌（adenoid cystic carcinoma,ACC）属于涎腺上皮性恶性肿瘤,术前易漏、误诊。ACC是以腺上皮、肌上皮细胞双相分化,具有管状、腺样和实性结构为特点,病程缓慢但长期预后不佳的涎腺恶性肿瘤^[1]。ACC术前诊断较难,术中冷冻病理检查难以确诊^[2]。由于ACC易出现复发和转移,局部大块切除是根治ACC的主要原则。因此,术前确诊对手术方式的选择非常重要。本科室采用细针吸取细胞学（fine needle aspiration cytology,FNA）检查并制作细胞块的方法,提高涎腺ACC的术前确诊率,现报道如下。     

涎腺腺样囊性癌中PD-L2的表达及临床意义

目的 探讨涎腺腺样囊性癌(salivary adenoid cystic carcinoma, SACC)组织中程序性死亡配体-2(programmed death-ligand 2, PD-L2)的表达及临床意义。方法 采用免疫组化EnVision法检测67例SACC中PD-L2的表达,免疫组化双染法检测PD-L2和CD68/CD163共表达情况,并分析PD-L2、CD68、CD163表达与SACC临床病理特征及预后的关系。结果 免疫组化结果显示,SACC肿瘤细胞和肿瘤浸润性免疫细胞(tumor-infiltrating immune cell, TIIC)中PD-L2的阳性率分别为17.9%(12/67)、53.7%(36/67)。肿瘤细胞以及TIIC的PD-L2表达均与淋巴结转移相关(P均<0.05),两者在有淋巴结转移组中PD-L2的表达高于无淋巴结转移组;肿瘤细胞以及TIIC中PD-L2的表达均与患者性别、年龄、肿瘤最大径、发病部位、主要结构、临床分期、神经侵犯以及脉管癌栓无关(P均>0.05)。免疫组化双染结果显示,部分TIIC PD-L2阳性细胞表达CD68和...     

涎腺腺样囊性癌的细胞学诊断及其与基底细胞腺瘤的鉴别北大核心CSCD

目的分析涎腺腺样囊性癌（ADCC）的细胞学形态特点,探讨涎腺ADCC与基底细胞腺瘤（BCA）的细胞学鉴别。方法回顾性分析首都医科大学附属北京同仁医院2010年1月至2017年1月头颈部30例涎腺ADCC及12例涎腺BCA的细胞学涂片／印片。除2例ADCC为针吸涂片外,余病例均为组织印片。所有病例诊断均经组织学证实。结果ADCC的肿瘤性导管细胞呈三维簇状、实性片状或单个散在分布;半透明黏液小球常见（20／30,66．7％）;细胞核呈圆形、卵圆形,有不同程度（多为轻度）的异型性;核仁常见（21／30,70．0％）,部分病例核仁明显;瘤细胞胞质稀少。ADCC细胞核的异型性具体表现在：（1）核染色深,核染色质粗或略粗、分布不均;（2）细胞核略大,且大小不一;（3）细胞核形状有不同程度（常为轻度）的不规则。核分裂象少见,30例ADCC均未见坏死。BCA细胞学形态特点部分与ADCC重叠,其与ADCC的不同之处主要在于：（1）单个散在分布的肿瘤性导管细胞少见：（2）半透明黏液小球少见（1／12）;（3）细胞核染色浅或略深,形状规则一致、大小均一、无异型性,较ADCC者小且更为细长,无核仁或见不明显小核仁;（4）瘤细胞胞质较ADCC丰富。结论涎腺ADCC与BCA细胞学表现既相互重叠又各有特点,绝大多数病例可通过细胞学诊断、鉴别。半透明黏液小球是细胞学诊断ADCC的重要线索,但不是该肿瘤的特异性改变。肿瘤性导管细胞核的异型性是诊断ADCC的必要条件,也是鉴别ADCC与BCA可靠的细胞学指标。     

Hybrid carcinoma of the salivary gland: salivary duct adenocarcinoma adenoid cystic carcinoma

AIMS: Hybrid tumours of the salivary gland are rare neoplasms that have been described only in the parotid and palate. Their recognition is important particularly when the component tumours have different biological behaviours. The occurrence of a submandibular hybrid tumour has not been reported. METHODS AND RESULTS: We describe a case of a 36-year-old woman with a hybrid carcinoma composed of salivary duct adenocarcinoma and adenoid cystic carcinoma of the right submandibular gland. There was no evidence of a pre-existing or concurrent pleomorphic adenoma. The presence of the two components was verified by differential immunohistochemical staining using a panel of cytokeratin, vimentin, smooth muscle actin and S100. The patient subsequently developed metastases to the pelvis, lumbar, vertebra and wrist. The clinical course in this patient was consistent with the behaviour of the salivary duct adenocarcinoma component. CONCLUSIONS: The histogenesis of hybrid tumours is largely unknown, but in this case it may represent diverging differentiation of luminal tumour cells. Because some histological features of different salivary gland tumours overlap, immunohistochemistry is a valuable tool especially when used to delineate the components of a hybrid tumour.     

DNA analysis at p53 locus in adenoid cystic carcinoma: Comparison of molecular study and p53 immunostaining

Abnormalities of the p53 tumor suppressor gene were investigated in 22 foci from 14 adenoid cystic carcinomas (ACC) by polymerase chain reaction (PCR)-based assays for dinucleotide (CA)_n and pentanucleotide (AAAAT)_n repeat polymorphisms and by immunohistochemical staining for oncoprotein expression. Adenoid cystic carcinomas were divided into lower grade (tubular and cribriform) subtypes and higher grade (trabecular and solid) subtypes. Histologically identified tumor cells were precisely microdissected from archival microslides and were used for molecular analysis. The overall frequency of p53 gene mutations detected by PCR-loss-of-heterozygosity (LOH) analysis was 57% and was higher than the frequency of overexpression of p53 oncoprotein detected by immunostaining (43%). In the molecular analysis of individual histological subtype foci, the number of foci with p53 gene mutation was slgnificantly greater in the higher grade subtype foci than in the lower grade subtype foci and was greatest in solid-type foci (100%). In all six tumors in which histologically different foci were present In the Same tumors, mutations of the p53 gene were detected. When tumor heterogeneity of the p53 gene was present among different histological foci in the same tumors, the mutations were always detected in the higher grade foci. When lower and higher grade foci were present in the same tumors, the identical mutations detected In the lower grade foci were present in the corresponding higher grade foci. These findings indicate that abnormaliies of the p53 gene are involved in carcinogenesis and/or progression of this tumor and, furthermore, suggest that molecular analyses of ACC may provide information of prognostic importance.     

Prognostic value of apoptosis and apoptosis-associated proteins in salivary gland adenoid cystic carcinoma

The purpose of the present study was to investigate the level of apoptosis and expressions of p53, mdm2 and bcl-2 proteins in salivary gland adenoid cystic carcinoma (ACC) to determine potential relationships among apoptosis, apoptosis-associated proteins and clinical cumulative survival. Thirty-nine formalin-fixed, paraffin-embedded cases, cribriform (17), tubular (13) and solid (9), were studied by immunohistochemistry. Apoptosis detection and analysis were determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). There was an inverse significance between the apoptotic index (AI) and bcl-2 expression (P = 0.018), whereas no correlation was found between the AI and either p53 or mdm2 expression (P = 0.416 and P = 0.456). Co-expression of p53 and mdm2 was found in 22 cases (P = 0.037). Patients with p53-positive tumors had a worse prognosis than those with p53-negative tumors (P = 0.014). Patients with a high AI had a better cumulative survival than patients with a low AI (P = 0.038). The present study suggests that p53 expression and AI can be useful as prognostic values; bcl-2 protein plays a role in the down-regulation of apoptosis and is also potentially useful as a prognostic parameter in salivary gland ACC.     

唾液腺腺样囊性癌中相关微小RNAs及其靶基因的生物信息学分析

目的 探讨唾液腺腺样囊性癌(SACC)潜在的微小RNAs(miRNAs)分子标志物,构建miRNA-mRNA调控网络,并阐明其潜在的分子机制.方法 从Gene Expression Omnibus(GEO)数据库下载2个SACC的微阵列芯片数据,通过R语言进行分析差异的miRNAs与mRNA.应用FunRich 3.1...     

Cytological features of dedifferentiated adenoid cystic carcinoma of the trachea

Adenoid cystic carcinoma (AdCC) is a distinct type of carcinoma, and cytological examination has been recognized as a useful tool in its diagnosis. Dedifferentiation is defined as the abrupt transformation of a low‐grade tumor into a tumor with high‐grade components. Albeit extremely rare, dedifferentiated AdCC has been reported: however, the cytological features of this tumor have not been documented. We observed a case in which a 66‐year‐old Japanese male had stenosis and thickness of the lower tracheal and bronchial walls. Cytological smears of a bronchial brush specimen revealed features typical for low‐grade AdCC. However, a few cohesive epithelial cell clusters composed of large, atypical polygonal cells with large nuclei and conspicuous nucleoli also were present. This component was considered to represent dedifferentiated carcinoma. Histopathological study of the resected bronchial tumor revealed dedifferentiated AdCC. The cytological diagnosis of conventional low‐grade AdCC is straightforward in most cases, although extremely rare, dedifferentiated carcinoma can occur within the conventional AdCC, and detection of a dedifferentiated component is possible in a cytological specimen because of obvious nuclear atypia. Therefore, careful observation is needed because cytologic diagnosis of dedifferentiated AdCC can help expedite treatment of this highly aggressive tumor. Diagn. Cytopathol. 2014;42:880–883. © 2013 Wiley Periodicals, Inc.     

RNAi knockdown of C-erbB2 expression inhibits salivary gland adenoid cystic carcinoma SACC-83 cell growth in vitro

Objective

To knockdown the C-erbB2 gene in salivary gland adenoid cystic carcinoma SACC-83 cells using RNA interference, and determine the effect of silencing C-erbB2 on cell proliferation.

Methods

C-erbB2-siRNA was transfected into SACC-83 cells. RT-PCR and immunohistochemistry were used to detect C-erbB2 expression in SACC-83 cells. Cell proliferation was measured by the MTT assay and gene knockdown was achieved by RNA interference. Apoptosis was analyzed by flow cytometry.

Results

Compared with the control, C-erbB2 mRNA expression was decreased in the C-erbB2-siRNA transfection group, and immunohistochemical analysis indicated that C-erbB2 protein expression was decreased. After C-erbB2-siRNA was transfected for 48 h, absorbance at 570 nm (MTT) was 0.185±0.021 compared with 0.354±0.034, 0.299±0.053, and 0.314±0.049 in the blank control, liposome control and negative control siRNA groups, respectively. The differences were statistically significant (P < 0.05) between the C-erbB2-siRNA group and the control groups. Following the C-erbB2 knockdown, the percentage of apoptotic cells was 5.63% compared with 2.04%, 2.85%, and 2.98% in the three control groups, respectively. Proliferation of SACC-83 cells was inhibited, and early apoptotic cells were increased.

Conclusion

RNA interference can effectively silence C-erbB2 gene expression and inhibit growth of SACC-83 cells, which indicates the potential of targeting this gene as a novel gene therapy approach for the treatment of salivary gland adenoid cystic carcinoma.     

Dedifferentiation of adenoid cystic carcinoma: Report of a case implicating p53 gene mutation

Adenoid cystic carcinoma is an indolent tumour with an unfavorable long-term prognosis. Dedifferentiation of adenoid cystic carcinoma, which is associated with an accelerated clinical course, has recently been described. We report a case with immunohistochemical and molecular workup to elucidate the likely mechanism of dedifferentiation. The patient, a 64-year-old woman, developed dedifferentiated adenoid cystic carcinoma of the submandibular gland ab initio, accompanied by cervical lymph node metastasis. Histologically, the low-grade adenoid cystic carcinoma merged gradually into an extensive dedifferentiated component that was composed of solid sheets and cords of anaplastic tumor cells with focal gland formation. Immunohistochemically, the dedifferentiated component, but not the adenoid cyst carcinoma component, showed strong overexpression of p53 protein and cyclin D1, as well as a higher Ki67 index. Molecular study confirmed the presence of p53 gene mutation selectively in the dedifferentiated component, suggesting a pivotal role of p53 gene alteration in the dedifferentiation process of adenoid cystic carcinoma.     

Stromal melanocytosis of an adenoid cystic carcinoma arising from the palatal minor salivary gland

An unusual case of adenoid cystic carcinoma arising from the palatal minor salivary gland in a 63-year-old Japanese female is reported. In addition to the characteristic histopath-ologic features of adenoid cystic carcinoma, spindle- and dendritic-shaped cells containing excessive amounts of melanin pigment were densely and widely distributed in the stroma resulting in a blue nevus-like appearance. Neither melanocytes nor melanin pigments were seen within the parenchyma. The possible histogenesis of melanocytes in the stroma of the salivary gland carcinoma is discussed, although no firm conclusion could be drawn.     

Hepatic metastasis as an initial manifestation of salivary adenoid cystic carcinoma: Cytologic diagnosis

Adenoid cystic carcinoma is a malignant tumor of the salivary glands. It is slow growing and is characterized by the delayed development of distant metastasis, which may develop even a decade or more after initial treatment of the primary tumor. We present the case of a 68-year-old male with complaints and radiological findings suggestive of primary hepatocellular carcinoma. However, fine-needle aspiration findings showed metastasis of adenoid cystic carcinoma. A retrospective clinical and ultrasound examination of the patient revealed a small asymptomatic enlargement of the submandibular salivary gland that was aspirated and showed features of adenoid cystic carcinoma.