腫瘤神經旁浸潤的研究進展△_《中國普外基礎與臨床雜志》

作者：

周濤 ,  呂成余 , 姚建洪 , 張一帆 , 陳維 , 袁愛華

南京醫科大學附屬南京第一醫院（南京市第一醫院）普外科（江蘇南京 210006）;

關鍵詞：

腫瘤神經旁浸潤定義分子機制

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　為進一步了解腫瘤神經旁浸潤（PNI）的概念、可能分子機制及臨床意義，以尋找新的腫瘤治療途徑。
方法　對有關PNI的定義、分子機制及臨床研究文獻進行綜述并分析。
結果　目前對于PNI被廣泛接受的定義是腫瘤接近并包繞至少33%神經周徑或者穿透三層神經鞘中的任意一層。PNI不僅僅是簡單的擴散，更像是浸潤和侵犯。目前主要有“低阻力通道”和“信號交互傳遞”兩種學說用以解釋其發生機制。近期的研究表明“信號交互傳遞”更能合理解釋PNI的發生機制。而包括成纖維細胞在內的基質成分，在促進PNI發生的復雜信號通路中起著關鍵作用；神經營養素和軸突導向分子在PNI的進程中起調節作用。臨床研究發現，PNI在頭頸部腫瘤、胃癌、胰腺癌、結直腸癌、前列腺癌等惡性腫瘤中是判斷預后的指標，陽性提示預后較差，5年存活率較低。
結論　PNI的發生機理極為復雜，關于其詳細的機理仍無明確的定論，故繼續這方面的研究將為揭開腫瘤PNI的機理提供理論基礎，也可為腫瘤的治療提供新的靶點。

引用本文： 周濤,呂成余,姚建洪,張一帆,陳維,袁愛華. 腫瘤神經旁浸潤的研究進展△. 中國普外基礎與臨床雜志, 2013, 20(5): 569-573. doi: 復制

1.	Cruveilhier J. Maladies des Nerfs：anatomie Pathologique du Corp Humain[M]. 2nd ed. Paris：Bailliere JB， 1835：1835-1842.
2.	Bilici A， Seker M， Ustaalioglu BB， et al. Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection[J]. Ann Surg Oncol， 2010， 17(8)：2037-2044.
3.	Liebig C， Ayala G， Wilks J， et al. Perineural invasion is an indep-endent predictor of outcome in colorectal cancer[J]. J Clin Oncol，.
4.	Saadat S， Barghouth I， Kazzazi A， et al. Risk factors associatedwith perineural invasion in prostate cancer[J]. Afr J Urol， 2012，.
5.	Loeb S， Epstein JI， Humphreys EB， et al. Does perineural invasion on prostate biopsy predict adverse prostatectomy outcomes?[J]. BJU Int， 2010， 105(11)：1510-1513.
6.	Stolinski C. Structure and composition of the outer connective tissue sheaths of peripheral nerve[J]. J Anat， 1995， 186(pt 1)：123-130.
7.	Batsakis JG. Nerves and neurotropic carcinomas[J]. Ann Otol Rhinol Laryngol， 1985， 94(4 pt 1)：426-427.
8.	Bockman DE， Büchler M， Beger HG. Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage[J]. Gastroenterology， 1994， 107(1)：219-230.
9.	Veness MJ. Perineural spread in head and neck skin cancer[J]. Australas J Dermatol， 2000， 41(2)：117-119.
10.	Liebig C， Ayala G， Wilks JA， et al. Perineural invasion in cancer：a review of the literature[J]. Cancer， 2009， 115(15)：3379-3391.
11.	Dunn M， Morgan MB， Beer TW. Perineural invasion：identification， significance， and a standardized definition[J]. Dermatol Surg， 2009， 35(2)：214-221.
12.	Liu H， Ma Q， Xu Q， et al. Therapeutic potential of perineural invasion， hypoxia and desmoplasia in pancreatic cancer[J]. Curr Pharm Des， 2012， 18(17)：2395-2403.
13.	Johnston M， Yu E， Kim J. Perineural invasion and spread in head and neck cancer[J]. Expert Rev Anticancer Ther， 2012， 12(3)：359-371.
14.	Ayala GE， Wheeler TM， Shine HD， et al. In vitro dorsal root ganglia and human prostate cell line interaction：redefining perineural invasion in prostate cancer[J]. Prostate， 2001， 49(3)：213-223.
15.	Ceyhan GO， Demir IE， Altintas B， et al. Neural invasion in panc-reatic cancer：a mutual tropism between neurons and cancer cells[J]. Biochem Biophys Res Commun， 2008， 374(3)：442-447.
16.	Cornell RJ， Rowley D， Wheeler T， et al. Neuroepithelial interactions in prostate cancer are enhanced in the presence ofprostatic stroma[J]. Urology， 2003， 61(4)：870-875.
17.	Chilton JK. Molecular mechanisms of axon guidance[J]. Dev Biol， 2006， 292(1)：13-24.
18.	(2)：82-86.
19.	Chédotal A， Kerjan G， Moreau-Fauvarque C. The brain within the tumor：new roles for axon guidance molecules in cancers[J]. Cell Death Differ， 2005， 12(8)：1044-1056.
20.	Boyd JG， Gordon T. Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury[J]. Mol Neurobiol， 2003， 27(3)：277-324.
21.	Dalal R， Djakiew D. Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate[J]. Mol Cell Endocrinol， 1997， 134(1)：15-22.
22.	Ketterer K， Rao S， Friess H， et al. Reverse transcription-PCR analysis of laser-captured cells points to potential paracrine and autocrine actions of neurotrophins in pancreatic cancer[J]. Clin Cancer Res， 2003， 9(14)：5127-5136.
23.	Okada Y， Eibl G， Guha S， et al. Nerve growth factor stimulates MMP-2 expression and activity and increases invasion by human pancreatic cancer cells[J]. Clin Exp Metastasis， 2004， 21(4)：285-292.
24.	Okada Y， Takeyama H， Sato M， et al. Experimental implication of celiac ganglionotropic invasion of pancreatic-cancer cells bearingc-ret proto-oncogene with reference to glial-cell-line-derived neuro-trophic factor (GDNF)[J]. Int J Cancer， 1999， 81(1)：67-73.
25.	Kurtz KA， Hoffman HT， Zimmerman MB， et al. Perineural and vascular invasion in oral cavity squamous carcinoma：increased incidence on re-review of slides and by using immunohistochemicalenhancement[J]. Arch Pathol Lab Med， 2005， 129(3)：354-359.
26.	Ling W， Mijiti A， Moming A. Survival pattern and prognostic factors of patients with squamous cell carcinoma of the tongue：a retrospective analysis of 210 cases[J]. Oral Maxillofac Surg， 2013， 71(4)：775-785.
27.	Brandwein-Gensler M， Teixeira MS， et al. Oral squamous cell carcinoma：histologic risk assessment， but not margin status， is strongly predictive of local disease-free and overall survival[J]. Am J Surg Pathol， 2005， 29(2)：167-178.
28.	Pilch BZ， Gillies E， Houck JR Jr， et al. Upper aerodigestic tract：Head and neck[M]. New York. College of AmericanPathologists， 2005：12-16.
29.	Luo TH， Fan GE， Bi JW， et al. The effect of perineural invasionon overall survival in patients with gastric carcinoma[J]. J Gastrointest Surg， 2008， 12(7)：1263-1267.
30.	謝洪虎，呂成余，黃文斌. 胃癌神經旁浸潤的臨床特征與預后分析[J]. 中華胃腸外科雜志， 2010， 13(6)：413-416.
31.	Ayala GE， Dai H， Ittmann M， et al. Growth and survival mechanisms associated with perineural invasion in prostate cancer[J].Cancer Res， 2004， 64(17)：6082-6090.
32.	Ahmad Z， Arshad H. Needle biopsy findings in prostatic adeno-carcinoma：experience at a tertiary care center in a developingcountry[J]. Ann Diagn Pathol， 2012， pii：S1092-9134(12)00148-00147.
33.	Lee IH， Roberts R， Shah RB， et al. Perineural invasion is a marker for pathologically advanced disease in localized prostate cancer[J]. Int J Radiat Oncol Biol Phys， 2007， 68(4)：1059-1064.
34.	Cartwright T， Richards DA， Boehm KA. Cancer of the pancreas：are we making progress? A review of studies in the US Oncology Research Network[J]. Cancer Control， 2008， 15(4)：308-313.
35.	Li J， Ma Q， Liu H， et al. Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia[J]. PLoS One， 2011， 6(2)：e17385.
36.	Ozaki H， Hiraoka T， Mizumoto R， et al. The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection[J]. Surg Today， 1999， 29(1)：16-22.
37.	Takahashi T， Ishikura H， Motohara T， et al. Perineural invasion by ductal adenocarcinoma of the pancreas[J]. J Surg Oncol， 1997， 65(3)：164-170.
38.	Peng J， Sheng W， Huang D， et al. Perineural invasion in pT3N0 rectal cancer：the incidence and its prognostic effect[J]. Cancer，.
39.	， 27(31)：5131-5137.
40.	， 117(7)：1415-1421.

1. Cruveilhier J. Maladies des Nerfs：anatomie Pathologique du Corp Humain[M]. 2nd ed. Paris：Bailliere JB， 1835：1835-1842.
2. Bilici A， Seker M， Ustaalioglu BB， et al. Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection[J]. Ann Surg Oncol， 2010， 17(8)：2037-2044.
3. Liebig C， Ayala G， Wilks J， et al. Perineural invasion is an indep-endent predictor of outcome in colorectal cancer[J]. J Clin Oncol，.
4. Saadat S， Barghouth I， Kazzazi A， et al. Risk factors associatedwith perineural invasion in prostate cancer[J]. Afr J Urol， 2012，.
5. Loeb S， Epstein JI， Humphreys EB， et al. Does perineural invasion on prostate biopsy predict adverse prostatectomy outcomes?[J]. BJU Int， 2010， 105(11)：1510-1513.
6. Stolinski C. Structure and composition of the outer connective tissue sheaths of peripheral nerve[J]. J Anat， 1995， 186(pt 1)：123-130.
7. Batsakis JG. Nerves and neurotropic carcinomas[J]. Ann Otol Rhinol Laryngol， 1985， 94(4 pt 1)：426-427.
8. Bockman DE， Büchler M， Beger HG. Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage[J]. Gastroenterology， 1994， 107(1)：219-230.
9. Veness MJ. Perineural spread in head and neck skin cancer[J]. Australas J Dermatol， 2000， 41(2)：117-119.
10. Liebig C， Ayala G， Wilks JA， et al. Perineural invasion in cancer：a review of the literature[J]. Cancer， 2009， 115(15)：3379-3391.
11. Dunn M， Morgan MB， Beer TW. Perineural invasion：identification， significance， and a standardized definition[J]. Dermatol Surg， 2009， 35(2)：214-221.
12. Liu H， Ma Q， Xu Q， et al. Therapeutic potential of perineural invasion， hypoxia and desmoplasia in pancreatic cancer[J]. Curr Pharm Des， 2012， 18(17)：2395-2403.
13. Johnston M， Yu E， Kim J. Perineural invasion and spread in head and neck cancer[J]. Expert Rev Anticancer Ther， 2012， 12(3)：359-371.
14. Ayala GE， Wheeler TM， Shine HD， et al. In vitro dorsal root ganglia and human prostate cell line interaction：redefining perineural invasion in prostate cancer[J]. Prostate， 2001， 49(3)：213-223.
15. Ceyhan GO， Demir IE， Altintas B， et al. Neural invasion in panc-reatic cancer：a mutual tropism between neurons and cancer cells[J]. Biochem Biophys Res Commun， 2008， 374(3)：442-447.
16. Cornell RJ， Rowley D， Wheeler T， et al. Neuroepithelial interactions in prostate cancer are enhanced in the presence ofprostatic stroma[J]. Urology， 2003， 61(4)：870-875.
17. Chilton JK. Molecular mechanisms of axon guidance[J]. Dev Biol， 2006， 292(1)：13-24.
18. (2)：82-86.
19. Chédotal A， Kerjan G， Moreau-Fauvarque C. The brain within the tumor：new roles for axon guidance molecules in cancers[J]. Cell Death Differ， 2005， 12(8)：1044-1056.
20. Boyd JG， Gordon T. Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury[J]. Mol Neurobiol， 2003， 27(3)：277-324.
21. Dalal R， Djakiew D. Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate[J]. Mol Cell Endocrinol， 1997， 134(1)：15-22.
22. Ketterer K， Rao S， Friess H， et al. Reverse transcription-PCR analysis of laser-captured cells points to potential paracrine and autocrine actions of neurotrophins in pancreatic cancer[J]. Clin Cancer Res， 2003， 9(14)：5127-5136.
23. Okada Y， Eibl G， Guha S， et al. Nerve growth factor stimulates MMP-2 expression and activity and increases invasion by human pancreatic cancer cells[J]. Clin Exp Metastasis， 2004， 21(4)：285-292.
24. Okada Y， Takeyama H， Sato M， et al. Experimental implication of celiac ganglionotropic invasion of pancreatic-cancer cells bearingc-ret proto-oncogene with reference to glial-cell-line-derived neuro-trophic factor (GDNF)[J]. Int J Cancer， 1999， 81(1)：67-73.
25. Kurtz KA， Hoffman HT， Zimmerman MB， et al. Perineural and vascular invasion in oral cavity squamous carcinoma：increased incidence on re-review of slides and by using immunohistochemicalenhancement[J]. Arch Pathol Lab Med， 2005， 129(3)：354-359.
26. Ling W， Mijiti A， Moming A. Survival pattern and prognostic factors of patients with squamous cell carcinoma of the tongue：a retrospective analysis of 210 cases[J]. Oral Maxillofac Surg， 2013， 71(4)：775-785.
27. Brandwein-Gensler M， Teixeira MS， et al. Oral squamous cell carcinoma：histologic risk assessment， but not margin status， is strongly predictive of local disease-free and overall survival[J]. Am J Surg Pathol， 2005， 29(2)：167-178.
28. Pilch BZ， Gillies E， Houck JR Jr， et al. Upper aerodigestic tract：Head and neck[M]. New York. College of AmericanPathologists， 2005：12-16.
29. Luo TH， Fan GE， Bi JW， et al. The effect of perineural invasionon overall survival in patients with gastric carcinoma[J]. J Gastrointest Surg， 2008， 12(7)：1263-1267.
30. 謝洪虎，呂成余，黃文斌. 胃癌神經旁浸潤的臨床特征與預后分析[J]. 中華胃腸外科雜志， 2010， 13(6)：413-416.
31. Ayala GE， Dai H， Ittmann M， et al. Growth and survival mechanisms associated with perineural invasion in prostate cancer[J].Cancer Res， 2004， 64(17)：6082-6090.
32. Ahmad Z， Arshad H. Needle biopsy findings in prostatic adeno-carcinoma：experience at a tertiary care center in a developingcountry[J]. Ann Diagn Pathol， 2012， pii：S1092-9134(12)00148-00147.
33. Lee IH， Roberts R， Shah RB， et al. Perineural invasion is a marker for pathologically advanced disease in localized prostate cancer[J]. Int J Radiat Oncol Biol Phys， 2007， 68(4)：1059-1064.
34. Cartwright T， Richards DA， Boehm KA. Cancer of the pancreas：are we making progress? A review of studies in the US Oncology Research Network[J]. Cancer Control， 2008， 15(4)：308-313.
35. Li J， Ma Q， Liu H， et al. Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia[J]. PLoS One， 2011， 6(2)：e17385.
36. Ozaki H， Hiraoka T， Mizumoto R， et al. The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection[J]. Surg Today， 1999， 29(1)：16-22.
37. Takahashi T， Ishikura H， Motohara T， et al. Perineural invasion by ductal adenocarcinoma of the pancreas[J]. J Surg Oncol， 1997， 65(3)：164-170.
38. Peng J， Sheng W， Huang D， et al. Perineural invasion in pT3N0 rectal cancer：the incidence and its prognostic effect[J]. Cancer，.
39. ， 27(31)：5131-5137.
40. ， 117(7)：1415-1421.

《中國普外基礎與臨床雜志》

腫瘤神經旁浸潤的研究進展△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

下一篇

Format

Content

《中國普外基礎與臨床雜志》

腫瘤神經旁浸潤的研究進展△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

下一篇

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料