Digestive Diseases and Sciences

, Volume 57, Issue 2, pp 364–370 | Cite as

Localization of Nerve Fibers in Colonic Polyps, Adenomas, and Adenocarcinomas by Immunocytochemical Staining for PGP 9.5

  • Tatsuo Tomita
Original Article



PGP 9.5 is a cytoplasmic protein and is a specific marker for neurites and neurons.


Using anti-PGP 9.5, this study aimed to localize nerve fibers in normal colons, polyps, adenomas and adenocarcinomas.


Colonic polyps, adenomas and T1 to T3 adenocarcinomas with adjacent normal colon were immunostained for PGP 9.5 using rabbit anti-PGP 9.5.


In normal colon, numerous nerve fibers were localized in inner and outer muscles, from which submucosa and lamina propria were innervated. In hyperplastic polyps and tubular adenomas, the stalk revealed Meissner’s plexus and large-diameter nerve fibers, and fine nerve fibers innervated abundantly in lamina propria of hyperplastic polyps and small tubular adenomas. In villous adenomas, large-diameter nerve fibers and Meissner’s plexus were localized in the stalk whereas a few or no fine nerve fibers were localized in fine stroma. In adenocarcinomas, more fine fibers were localized in submucosal stroma adjacent to the invading carcinoma in T1 carcinomas but there were no nerve fibers in the midst of tumors in T2 and T3 carcinomas. There were focally and sporadically increased nerve fibers adjacent to invading cancer nests in 5 of 8 T2 cases. In T3 carcinomas, fragmented Auerbach’s plexus were noted in cancer-invaded colonic muscles and there were no increased fine nerve fibers in the cancer-invaded subserosa in the majority of cases. PGP 9.5 immunostaining revealed tumor-associated neurogenesis in submucosa but no obviously increased nerve fibers within cancer-invaded muscles.


This lack of tumor-associated neurogenesis supports insidious and often silent clinical presentation of colonic carcinomas until invading through the colonic wall to adjacent organs.


Colonic adenoma Adenocarcinoma Colonic carcinoma Immunocytochemistry Nerve PGP 9.5 



I sincerely thank Dr Ov Slayden for allowing me to use his research laboratory to perform immununocytochemical staining at Reproductive Science Division, Oregon National Primate Center, Beaverton, OR. This study was supported in part by ONRRC Core Grant NIH RR 000163.


  1. 1.
    Hoyle CHV, Burnstock G. Neuronal populations in the submucous plexus of the human colon. J Anat. 1989;166:7–22.PubMedGoogle Scholar
  2. 2.
    Irwin DA. The anatomy of Auerbach’s plexus. Am J Anat. 2005;49:141–166.CrossRefGoogle Scholar
  3. 3.
    Jackson P, Thompson RJ. The demonstration of new human brain-specific proteins by high two-dimensional polyacrylamide gel electrophoresis. J Neural Sci. 1981;49:429–438.CrossRefGoogle Scholar
  4. 4.
    Thompson RJ, Doran JF, Jackson P, et al. PGP 9.5—a new member for vertebrate neurons and neuroendocrine cells. Brain Res. 1983;278:224–228.PubMedCrossRefGoogle Scholar
  5. 5.
    Wilkinson KD, Lee KM, Deschpande S, et al. The neuron specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydroxylase. Science. 1989;246:670–673.PubMedCrossRefGoogle Scholar
  6. 6.
    Karanth SS, Springall DR, Kuhn DM, et al. An immunocytochemical study of cutaneous innervations and the distribution of neuropeptides and protein gene product 9.5 in man and commonly employed laboratory animals. Am J Anat. 1991;191:369–383.PubMedCrossRefGoogle Scholar
  7. 7.
    Michell BS, Schumacher U, Kaiserling E. Are tumours innervated? Immunohistological investigation using antibodies against the neuronal marker protein gene product 9.5 in benign, malignant and experimental tumours. Tumor Biol. 1994;15:269–274.CrossRefGoogle Scholar
  8. 8.
    Chamary VL, Robson T, Loizidou M, et al. Progressive loss of perivascular nerve adjacent to colorectal cancer. Eur J Surg Oncol. 2000;26:588–593.PubMedCrossRefGoogle Scholar
  9. 9.
    Compton CC. Colorectal carcinoma: diagnostic, prognostic, and molecular features. Mod Pathol. 2003;16:376–388.PubMedCrossRefGoogle Scholar
  10. 10.
    Sobin LH, Wittekind CH. Colon and rectum. In: Sobin LH, Wittekind CH, eds. TNM Classification of Malignant Tumours. Geneva: Wiley, UICC; 2002:72–76.Google Scholar
  11. 11.
    Tomita T. Immunocytochemical localization of lymphatic vessels in colonic polyps and adenomas. Dig Dis Sci. 2008;53:1880–1885.PubMedCrossRefGoogle Scholar
  12. 12.
    Vonlaufen A, Wiedle G, Borisch B, et al. Integrin alpha beta expression in colon carcinoma correlates with survival. Mod Pathol. 2001;14:1126–1132.PubMedCrossRefGoogle Scholar
  13. 13.
    Zimmerman RL, Ross HM, Causas RE. Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel D2–40. Oncol Rep. 2004;11:47–50.PubMedGoogle Scholar
  14. 14.
    Rmali KA, Puntis CA, Jiang WG, et al. Tumour-associated angiogenesis in human colorectal cancer. Colorec Dis. 2006;9:3–14.CrossRefGoogle Scholar
  15. 15.
    Sundlisaeter E, Dicko A, Sakariassen O, et al. Lymphangiogenesis in colorectal cancer- prognostic and therapeutic aspects. Int J Cancer. 2007;121:1401–1409.PubMedCrossRefGoogle Scholar
  16. 16.
    Fujita S, Nakanisi Y, Taniguchi H, et al. Cancer invasion to Auerbach’s plexus is an important prognostic factor in patients with pT3-pT4 colorectal cancer. Dis Colon Rectum. 2007;50:1860–1866.PubMedCrossRefGoogle Scholar
  17. 17.
    Yamazaki T, Hibi K, Takase T, et al. PGP9.5 as a marker for invasive colorectal cancer. Clin Cancer Res. 2002;8:192–195.PubMedGoogle Scholar
  18. 18.
    Martin R, Fraile B, Peinadeo F, et al. Immunohistochemical localization of PGP 9.5, ubiquitin and NPY immunoreactivities in epithelial and neuroendocrine cells from normal and hyperplastic human prostate. J Histochem Cytochem. 2000;48:1121–1130.PubMedCrossRefGoogle Scholar
  19. 19.
    Liblich A, Cross SS, Catto JWF, et al. Human prostate cancer cells express neuroendocrine cell marker PGP 9.5 and chromogranin A. Prostate. 2007;67:1761–1769.CrossRefGoogle Scholar
  20. 20.
    Ansari P. Acute abdominal pain. In: Porter RS, Kaplan JL, eds. Merck Manual of Diganosis and Therapy. Whitehouse Station, NJ: Merck and Company; 2007:1–6.Google Scholar
  21. 21.
    Cappell MS. Pathophysiology, clinical presentation and management of colon cancer. Gastroenterol Clin NA. 2008;37:1–24.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Pathology and Oregon National Primate CenterOregon Health and Science UniversityPortlandUSA
  2. 2.Oregon National Primate CenterBeavertonUSA

Personalised recommendations