Research Progression of Perineural Invasion of Tumor_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHOU Tao ,  LU Chengyu , YAO Jianhong , ZHANG Yifan , CHEN Wei , YUAN Aihua

Department of General Surgery， The First Affiliated Nanjing Hospital of Nanjing Medical University， Nanjing 210006， Jiangsu Province， China;

Corresponding author：

LU Chengyu, Email: lcy_1234@yahoo.com.cn

Keywords：

Tumor; Perineural invasion; Definition; Molecular mechanism

Video：

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Objective 　To further comprehend the definition， molecular mechanism， and clinical significance of perineural invasion （PNI） so as to explore new therapy for the tumors.
Methods 　The literatures about the definition， molecular mechanism， and clinical study of PNI were reviewed and analyzed.
Results 　At present， widely accepted definition of PNI was that at least 33% of the circumference of the nerve should be surrounded by tumor cells or tumor cells within any of three layers of the nerve sheath. The newest theory on molecular mechanism of PNI was that PNI was more like infiltration， invasion， not just diffusion. “Path of low-resistance” and “Reciprocal signaling interactions” were the main theories. More recently， the studies had demonstrated that “Reciprocal signaling interactions” could more clearly explain the mechanism of PNI. Stromal elements， including fibroblasts， seemed to play a key role in the complex signaling interactions driving PNI. Neurotrophins and axonal guidance molecules had been implicated in promoting the progress of PNI. PNI was a prognosis index in the cancers of the head and neck， stomach， pancreas， colon and rectum， and prostate， which was positive indicated that the patients would have a poor prognosis and a low 5-year survival rate.
Conclusions 　The mechanism of PNI is very complex， and its clear mechanism is still undefined. Keeping on researching the mechanism of PNI could provide theoretical foundation to disclose the mechanism and the therapy of PNI.

Citation： ZHOU Tao,LU Chengyu,YAO Jianhong,ZHANG Yifan,CHEN Wei,YUAN Aihua. Research Progression of Perineural Invasion of Tumor. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(5): 569-573. doi: Copy

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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.
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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.
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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.
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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.	谢洪虎，吕成余，黄文斌. 胃癌神经旁浸润的临床特征与预后分析[J]. 中华胃肠外科杂志， 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. 谢洪虎，吕成余，黄文斌. 胃癌神经旁浸润的临床特征与预后分析[J]. 中华胃肠外科杂志， 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.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Progression of Perineural Invasion of Tumor

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