胰腺癌细胞的嗜神经性与神经周浸润机理的研究进展

目的综述胰腺癌细胞神经周浸润(perineural invasion,PNI)的发生机理,为胰腺癌治疗寻找新的靶点。方法对包含有关胰腺癌PNI、嗜神经浸润、神经-肿瘤微环境和神经生长因子的文献进行分析,总结有关PNI的发生机理。结果胰腺组织本身具有的丰富神经支配和神经纤维鞘具有裂隙样的结构是PNI的解剖基础。癌细胞表达神经源性标志物或获得嗜神经浸润表型可能是PNI的病理基础。肿瘤-神经微环境或神经生长因子家族及其相应受体可能是PNI的分子基础。对于PNI,不仅仅在于癌细胞本身具有的嗜神经浸润能力,也可能是癌细胞和神经纤维之间相互作用的结果。结论 PNI的机理较复杂,尚没有明确的定论,但相关机理将可能为胰腺癌的治疗提供新的靶点。     

恶性肿瘤外周神经转移研究进展

【摘要】〓外周神经浸润(PNI)与多种类型肿瘤转移、复发关系密切,是独立预后不良因素。本文从明确PNI概念开始,综述目前PNI分子和病理机制、体外内模型建立等研究进展,旨在更深入地了解PNI在肿瘤转移、复发中的作用,为进一步研究PNI机制及开发靶向PNI治疗策略奠定基础。     

前列腺癌神经侵犯的研究现状摆俊博1,陶宁2,安恒庆1,

前列腺癌神经周围浸润(PNI)发生率较高,其发生与手术根治程度及术后复发密切相关。本文将对有关前列腺癌PNI机制的研究现状以及PNI与病理、预后、前列腺癌根治手术的关系作一综述,阐述PNI在前列腺癌发展中的影响。     

消化道恶性肿瘤的周围神经浸润研究进展

消化道恶性肿瘤病人的生存时间决定于肿瘤的生物学特点及肿瘤的分期目前,临床普遍采用的肿瘤分期是TNM分期。而研究表明,除TNM分期外,还有一些独立的预后判断指标值得关注如周围神经浸润(perineural invasionPNI)等。肿瘤的周围神经浸润是指肿瘤细胞侵犯局部邻近的神经的神经束膜或神经肌束。在消化道恶性肿瘤中PNI多见于胰腺癌和胆道系统的恶性肿瘤,偶尔出现在直肠癌中,被认为是肿瘤的局部扩散方式之一,对判断预后也有重要作用[1]。PNI最早在前列腺癌的研究中被发现,是最常见也是最重要的前列腺癌局部生长的方式之一。因此,PNI不仅…     

胃癌神经旁浸润的临床特征与预后分析

目的 探讨胃癌神经旁浸润（PNI）的临床意义.方法 对2004年1月至2008年5月期间178例行胃癌根治术后的胃癌组织石蜡标本行苏木精-伊红染色,以肿瘤细胞浸润神经束或神经束膜判定为PNI阳性.分析PNI与胃癌临床病理特征及预后的关系.结果 PNI阳性78例（43.8%）.PNI与肿瘤浸润深度（P＜0.01）、淋巴结转移（P＜0.01）和TNM分期（P＜0.01）有关,但与患者的年龄、性别、肿瘤位置和分化程度无关.单因素分析显示,胃癌患者总体生存率与PNI、胃癌浸润深度、淋巴结转移和TNM分期有关（均P＜0.01）;PNI阳性患者平均生存期（28.6个月）明显短于PNI阴性患者（44.3个月）（P＜0.01）.多因素分析显示,PNI是影响患者总体生存率的独立因素（相对危险度为2.257,95%CI为1.268～4.019,P=0.006）.结论 PNI与肿瘤的进展有关,胃癌术后检测PNI可以作为判断患者预后指标之一.     

结直肠癌神经浸润的研究进展

神经浸润是造成结直肠恶性肿瘤术后复发及远处转移的重要影响因素,对患者预后影响较大,但目前对与结直肠癌神经浸润的研究较少,发生机制尚未明确。本文结合国内外相关研究,对结直肠癌神经浸润的定义、发病机制、诊断方法及临床意义进行分析和总结,为结直肠癌神经浸润的诊断及治疗提供更完善的的理论依据。     

直肠癌神经周围浸润的临床研究

目的 探讨直肠癌神经周嗣浸润（PNI）的临床意义.方法 回顾性分析郴州市第一人民医院2003年1月至2005年1月间行直肠前切除低位吻合术（Dixon）的204例直肠癌患者的临床资料,标本常规石蜡切片后行苏木精-伊红染色,以肿瘤细胞浸润神经束或神经束膜判定为PNI阳性.分析PNI与直肠癌临床病理特征和预后的关系.结果 204例直肠癌患者中PIN阳性65例（31.9%）.PNI与肿瘤大小、浸润深度、淋巴结转移、TNM分期、肿瘤生长方式、分化程度、肿瘤切除情况有关（P＜0.05）.PNI阳性组患者术后生存时间为（43.8±1.5）个月,明显短于PNI阴性组的（57.2±1.5）个月（P＜0.01）.PNI阳性的Ⅱ期患者术后平均生存时间为（46.5±3.2）个月,显著低于Ⅲ期患者的（55.7±1.2）个月（P＜0.05）.结论 PNI可作为直肠癌的预后判断指标.     

胃癌局部神经侵犯的临床研究

目的：探讨胃癌局部神经侵犯（PNI）的临床意义。方法：对110例胃癌根治手术的病理组织行苏木素-伊红染色,肿瘤细胞侵犯神经束或神经束膜为PNI阳性。结果：110例中PNI阳性49例,PNI与肿瘤大小、浸润深度、区域淋巴结转移、TNM分期、脉管癌栓、断端阳性有显著相关性,与性别、年龄、肿瘤部位及远处转移无相关性。结论：胃癌周围神经侵犯与肿瘤的进展密切相关,但不是影响预后的独立因素。     

神经旁浸润对胃癌根治术后患者预后的影响

目的：探讨神经旁浸润（PNI）对胃癌患者行根治性切除术后预后的影响。方法回顾性分析252例行胃癌根治术后的患者的临床资料。胃癌组织的石蜡标本以苏木精伊红（HE）染色,当肿瘤细胞浸润神经束膜或神经束内时判断为PNI阳性。分析PNI与其他临床病理特征之间的关系及其对患者预后的影响。结果 PNI阳性率32．1％（81／252）。PNI阳性率与T分期、N分期、TNM分期、肿瘤分化程度、血管和淋巴管侵犯及Lauren分型有关（P＜0．05）,与患者的性别、年龄、肿瘤大小、肿瘤部位及Borrmann分型无关（P＞0．05）。随着肿瘤的进展,PNI阳性率增高。PNI阳性患者的5年累积生存率与平均生存时间分别为23．9％和34．5个月,明显低于PNI阴性患者的43．6％与43．8个月,差异有统计学意义（χ2＝11．765,P＝0．001）。多因素分析显示,PNI是影响患者预后的独立因素（P＝0．023,HR＝0．182,95％CI 0．042～0．793）。结论胃癌患者的PNI阳性率较高,PNI与胃癌的进展有关,是胃癌患者预后不良的标志之一。     

胃癌神经侵犯的相关临床病理因素：单中心509例分析

目的:分析胃癌患者神经侵犯(PNI)的相关临床病理因素。方法:收集江苏大学附属医院2014年6月—2017年6月509例胃癌患者的临床和病理资料,分析PNI与患者临床病理因素的关系。结果:509例胃癌患者中,神经侵犯阳性患者250例,阴性患者259例。单因素分析显示,胃癌PNI与肿瘤浸润深度、组织分化程度、淋巴结转移和TNM分期有关(均P0.001),而与患者年龄、性别无关(均P0.05);趋势χ~2检验显示胃癌PNI与肿瘤浸润深度相关性最大(r=0.623,P0.001);二分类Logistic回归分析表明肿瘤浸润深度为胃癌神经侵犯的独立危险因素(OR=6.285,95%CI=4.009~9.854,P0.001)。结论:胃癌患者PNI与肿瘤浸润深度、组织分化程度、淋巴结转移数目和TNM分期有关,其中肿瘤浸润深度可能是最重要的因素。     

The Effect of Perineural Invasion on Overall Survival in Patients with Gastric Carcinoma

Aims  The availability of different treatment options for gastric carcinoma has reopened the question of correct definition of high-risk categories, which may help in identifying patients with high risk for poor prognosis who would benefit more from adjuvant therapy after operation. Perineural invasion (PNI) seems to provide useful information for management. Therefore, we examined the effect of PNI on overall survival (OS) in patients with gastric carcinoma and the association between PNI and other clinical and pathological factors. Patients and Methods  A total of 1,632 patients with gastric carcinoma from 2000 to 2005 were analyzed retrospectively. Paraffin sections of surgical specimens from all patients who underwent gastric resection were stained with laminin. If carcinoma cells infiltrated into the perineurium or neural fascicles, PNI was assessed as positive. Survival analysis was done in 1,372 patients with T1–T4 tumors who underwent curative resection. Result  PNI was positive in 518 of the 1,632 patients (31.7%). The size of tumors, T stage, differentiation of tumor, and clinical stage were significantly related to PNI positivity. The proportion of large tumors was significantly higher in PNI-positive patients than in PNI-negative patients (P < 0.01). As the depth of gastric mural invasion or clinical stage increased, the positive rate of PNI also increased. The OS of the PNI-positive patients was significantly shorter than that of the PNI-negative patients in the univariate analysis (P < 0.01). At multivariate Cox proportional hazards model of OS analysis, the positivity of PNI appeared to be an independent prognostic factor for OS (hazards ratio [HR] = 3.23, 95%CI = 2.6–8.11, P < 0.01), which was also influenced by tumor differentiation, T stage, and clinical stage (P < 0.01). Conclusion  Our results suggested that the incidence of PNI was high in gastric carcinoma and that it corresponded to the progression of disease. It could provide additional information for identifying patients who are at high risk for poor prognosis. PNI can be a candidate for a new kind of prognostic parameters.     

p75NGFR Immunostaining for the Detection of Perineural Invasion by Cutaneous Squamous Cell Carcinoma

BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) may portend a poor prognosis for patients. p75NGFR (nerve growth factor receptor) is part of a membrane receptor complex that binds nerve growth factor. Its use for detecting PNI in CSCC in comparison with S-100 immunohistochemical staining has not been explored. OBJECTIVE : To determine whether detection of PNI may be improved by staining with p75NGFR compared with hematoxylin and eosin (H&E) and S-100. METHODS: Thirty-four cases of CSCC were retrospectively evaluated for the presence of PNI using standard H&E, as well as S-100 and p75NGFR immunohistochemical stains. Staining intensity was correlated to the presence or absence of PNI and tumor differentiation. RESULTS: The results showed a positive correlation between staining intensity and the presence of PNI detected by p75NGFR (p=.04). Using p75NGFR allowed for the detection of seven cases of PNI not detected by H&E alone. Five of these cases were detected by S-100, with two cases seen by p75NGFR only. Six cases of PNI were detected using S-100 not seen on H&E, with one case also not seen using p75NGFR. CONCLUSION: p75NGFR immunostaining increased detection of PNI compared with H&E. p75NGFR could serve as an alternative to S-100 in the detection of PNI or as part of an immunostaining panel for PNI detection.     

ֱ�����񾭽���Ԥ���о�

??Affact of perineural invasion on the prognosis of patients with rectum cancer FAN Ping, TIAN Jing-zhong, LI Guang-yun, et al. Department of General Surgery, Bozhou People’s Hospital, Bozhou236800, China Corresponding author: FAN Ping, E-mail: dengfang1992@sina.com Abstract Objective To analyze the effect of perineural invasion on evaluating the prognosis of patients with rectal cancer. Methods The clinical data of 213 patients with rectum cancer performed total mesorectal excision (TME) from 2000 to 2007 at Bozhou People’s Hospital were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent TME were stained with laminin. The effect of PNI on overall survival (OS) in patients with rectum cancer and the association between PNI and other clinical and pathological parameters were analyzed. Results PNI was positive in 62 of all the 213 patients (29.11%). The size of tumors, T stage and clinical stage were related to PNI significantly. The OS of the PNI-positive patients [??23.04±9.95??months] was shorter than that of the PNI-negative patients [??52.10±14.61??months] in the univariate analysis significantly (P<0.01). And at multivariate Cox proportional hazards model of OS analysis, the positivity of PNI appeared to be an independent prognostic factor to OS , which was also influenced by tumor size, lymph node metastasis and clinical stage (P<0.01). Conclusion The incidence of PNI plays an important role in evaluation of the tumor classification, stage and the prognosis of rectum cancer and it could serve as an independent predictor of prognosis of rectum cancer.     

Limited value of perineural invasion in radical prostatectomy specimens as a predictor of biochemical recurrence in Japanese men with clinically localized prostate cancer

The objective of this study was to determine whether the presence of perineural invasion (PNI) in radical prostatectomy specimens could be a useful prognostic parameter in Japanese men with prostate cancer. Between January 1995 and September 2003, 202 Japanese men underwent radical retropubic prostatectomy for prostate cancer without any neoadjuvant therapies prior to surgery. We retrospectively analyzed the relationship between PNI in radical prostatectomy specimens and other prognostic factors, and also assessed the significance of PNI in biochemical recurrence after radical prostatectomy. The presence of PNI was significantly related to clinical stage, pathological stage, Gleason score, seminal vesicle invasion, lymph node metastasis and tumor volume, but not pretreatment serum prostate specific antigen value. During the observation period, biochemical recurrence occurred in 20 patients (3 in patients without PNI and 17 in those with PNI), and the biochemical recurrence-free survival rate in patients with PNI was significantly lower than that in patients without PNI. In addition to-PNI, pathological stage, seminal vesicle invasion, lymph node metastasis and tumor volume were significantly associated with the biochemical recurrence-free survival rate; however, among these five factors, only seminal vesicle invasion was an independent predictor of biochemical recurrence on multivariate analysis. Despite a significant association between several prognostic parameters, PNI was not an independent predictor of biochemical recurrence; therefore, it may not provide an additive effect to consider the presence of PNI in predicting the prognosis of Japanese men who underwent radical prostatectomy if there are other conventional parameters available.     

LIMK与结直肠癌关系的研究进展

目的了解LIM激酶(LIMK)与结直肠癌的关系,为结直肠癌的转移、侵袭及靶向治疗提供研究依据。方法复习近年来国内外关于LIMK的结构功能以及其与结直肠癌关系研究进展的相关文献并加以综述。结果 LIMK及其主要通路ROCK/LIMK/cofilin及PAK/LIMK/cofilin上下游因子均参与了肿瘤细胞周期进展、肿瘤细胞侵袭、迁移、增殖等多种细胞生物学行为,如p21活化蛋白激酶4(PAK4)通过PAK4/LIMK1/cofilin信号通路参与细胞骨架动力学调节癌细胞迁移和侵袭,cofilin经过Rho/ROCK/LIMK1/cofilin通路影响肿瘤细胞运动和形态的变化,从而参与肿瘤细胞的侵袭和迁移;两种肿瘤转移相关蛋白MYH9和ACTN4为LIMK1的直接靶标,此三者相互作用可以促进结肠癌进展。LIMK家族的另一成员LIMK2可通过限制上皮间充质转化过程抑制细胞转移的能力,并与β-连环蛋白的核可激活Wnt信号传导途径,从而导致结肠癌进展和转移。二烯丙基二硫可以下调结肠癌细胞SW480中LIMK1的表达,抑制LIMK1/cofilin信号通路,阻碍血管生成和上皮间充质转化,抑制结肠癌的迁移和侵袭,而其他LIMK抑制剂暂未在结直肠癌中得到验证。结论结直肠癌及其转移的分子机制尚未完全阐明,通过对结直肠癌及其转移机制与LIMK关系的深入研究,可为结直肠癌及转移提供分子靶向治疗突破点,并有助于为探究结直肠癌的诊断、判断复发、预后及转移情况提供更多帮助。     

Criteria for extramural perineural invasion as a prognostic factor in rectal cancer.

BACKGROUND: An abundant extramural autonomic nerve network is an anatomical feature of the rectum. Extramural perineural invasion (PNI) may influence the prognosis after resection of rectal cancer, however, few assessment criteria exist. METHODS: PNI was investigated in 364 patients who underwent curative surgery for rectal cancer penetrating the muscular layer. A grading system was established based on the 'intensity' (number of PNI foci in a 20-power field) and 'depth' (distance from the muscularis propria) of PNI. PNI-0 was defined as without PNI, PNI-1 as 'intensity' of less than five foci and 'depth' less than 10 mm, and PNI-2 as five or more foci or 10 mm or greater 'depth' of invasion. RESULTS: PNI was observed in 52 patients (14 per cent) and strongly correlated with pathological tumour node metastasis (pTNM) stage. Five-year survival was related to PNI grade (74 per cent in PNI-0, 50 per cent in PNI-1 and 22 per cent in PNI-2). The rate of local recurrence was also related to PNI stage: 43 per cent in PNI-2 and 9 per cent in both PNI-0 and PNI-1. Multivariate analyses showed that graded PNI was associated both with local recurrence and long-term survival, independent of tumour depth (pTNM T) and nodal involvement (pTNM N). CONCLUSION: The PNI grading system may be useful in prognosis and allow case selection for intensive postoperative adjuvant therapy.