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

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Abstract

Background

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

Aims

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

Methods

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

Results

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.

Conclusions

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.

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References

  1. Hoyle CHV, Burnstock G. Neuronal populations in the submucous plexus of the human colon. J Anat. 1989;166:7–22.

    PubMed  CAS  Google Scholar 

  2. Irwin DA. The anatomy of Auerbach’s plexus. Am J Anat. 2005;49:141–166.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  9. Compton CC. Colorectal carcinoma: diagnostic, prognostic, and molecular features. Mod Pathol. 2003;16:376–388.

    Article  PubMed  Google Scholar 

  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. Tomita T. Immunocytochemical localization of lymphatic vessels in colonic polyps and adenomas. Dig Dis Sci. 2008;53:1880–1885.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  14. Rmali KA, Puntis CA, Jiang WG, et al. Tumour-associated angiogenesis in human colorectal cancer. Colorec Dis. 2006;9:3–14.

    Article  Google Scholar 

  15. Sundlisaeter E, Dicko A, Sakariassen O, et al. Lymphangiogenesis in colorectal cancer- prognostic and therapeutic aspects. Int J Cancer. 2007;121:1401–1409.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

  21. Cappell MS. Pathophysiology, clinical presentation and management of colon cancer. Gastroenterol Clin NA. 2008;37:1–24.

    Article  Google Scholar 

Download references

Acknowledgments

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.

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Correspondence to Tatsuo Tomita.

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Tomita, T. Localization of Nerve Fibers in Colonic Polyps, Adenomas, and Adenocarcinomas by Immunocytochemical Staining for PGP 9.5. Dig Dis Sci 57, 364–370 (2012). https://doi.org/10.1007/s10620-011-1876-7

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  • DOI: https://doi.org/10.1007/s10620-011-1876-7

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