Skip to main content
SpringerLink
Log in

Immunohistochemical evaluation of tissue-specific proteolytic enzymes in adenomas containing foci of early carcinoma

Correlations with cathepsin D expression and other malignant features

  • Research Article
  • Published:
International Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Background: Cathepsin D (CD) is an aspartyl lysosomal protease, and the prognostic value of CD expression has been studied in a variety of tumors, however, its role in early adenocarcinomas remains unclear.

Aim of the Study: We evaluated the expression of CD in a series of colorectal adenomas with severe dysplasia containing foci of early carcinoma and compared the results to several histopathological and immunohistochemical features.

Methods: Adenomas were obtained by endoscopic polypectomy from 33 patients. Twenty-four of the 33 adenomas contained well-differentiated adenocarcinomas and nine adenomas contained moderately differentiated adenocarcinomas.

Results: Positive CD expressions were observed in 25% of well-differentiated adenocarcinomas and in 66.7% of moderately differentiated adenocarcinomas (p<0.05). Of the 12 adenocarcinomas with positive CD expression, four had positive CD expression in their adenomas (p<0.01), 6 showed positive Ki-67 expression in their adenomas (NS), and 10 had positive p53 expression in their adenomas (p<0.05). No significant association was seen between the level of CD expression and adenoma size.

Conclusions: The expression of CD in adenocarcinoma correlated significantly with differentiation, and with the levels of CD and p53 expression in the adenomas of the polyp.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Liotta LA. Tumor invasion and metastases: role of the basement membrane. Warner-Lambert Parke-Davis Award Lecture. Am J Pathol 1984;117:339–348.

    PubMed  CAS  Google Scholar 

  2. Briozzo P, Morisset M, Capony F, et al. In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells. Cancer Res 1988;48:3688–3692.

    PubMed  CAS  Google Scholar 

  3. Nazeer T, Malfetano JH, Rosano TG, Ross JS. Correlation of tumor cytosol cathepsin D with differentiation and invasiveness of endometrial adenocarcinoma. Am J Clin Pathol 1992;97:764–769.

    PubMed  CAS  Google Scholar 

  4. Saku T, Sakai H, Tsuda N, et al. Cathepsins D and E in normal, metaplastic, dysplastic, and carcinomatous gastric tissue: an immunohistochemical study. Gut 1990;31:1250–1255.

    Article  Google Scholar 

  5. Valentini AM, Pirrelli M, Armentano R, Caruso ML. The immunohistochemical expression of cathepsin D in colorectal cancer. Anticancer Res 1996;16:77–80.

    PubMed  CAS  Google Scholar 

  6. Mayer A, Fritz E, Fortelny R, et al. Immunohistochemical evaluation of cathepsin D expression in colorectal cancer. Cancer Invest 1997;15:106–110.

    Article  PubMed  CAS  Google Scholar 

  7. Kanber Y, Demirbag NR, Sam AD, Aydin N. Cathepsin D expression in colorectal adenocarcinomas and adenomas. Int J Biol Markers 2002;17:165–168.

    PubMed  CAS  Google Scholar 

  8. Japanese Society for Cancer of the Colon and Rectum. Pathological rules, in General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus, 6th ed. Japan: Kanehara, Tokyo, 1998 (in Japanese).

  9. Ioachim EE, Goussia AC, Machera M, et al. Immunohistochemical evaluation of cathepsin D expression in colorectal tumours: a correlation with extracellular matrix components, p53, pRb, bcl-2, c-erbB-2, EGFR and proliferation indices. Anticancer Res 1999;19:2147–2155.

    PubMed  CAS  Google Scholar 

  10. Sedivy R, Wolf B, Kalipciyan M, et al. Genetic analysis of multiple synchronous lesions of the colon adenomacarcinoma sequence. Br J Cancer 2000;82:1276–1282.

    Article  PubMed  CAS  Google Scholar 

  11. Yao T, Kajiwara M, Kouzuki T, et al. Villous tumor of the colon and rectum with special reference to roles of p53 and bcl-2 in adenoma-carcinoma sequence. Pathol Int 1999;49:374–382.

    Article  PubMed  CAS  Google Scholar 

  12. Saleh HA, Jackson H, Khatib G, Banerjee M. Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia. Pathol Oncol Res 1999;5:273–279.

    Article  PubMed  CAS  Google Scholar 

  13. Kikuchi Y, Dinjens WN, Bosman FT. Proliferation and apoptosis in proliferative lesions of the colon and rectum. Virchows Arch 1997;431:111–117.

    Article  PubMed  CAS  Google Scholar 

  14. Johnston PG, O’Brien MJ, Dervan PA, Carney DN. Immunohistochemical analysis of cell kinetic parameters in colonic adenocarcinomas, adenomas, and normal mucosa. Hum Pathol 1989;20:696–700.

    Article  PubMed  CAS  Google Scholar 

  15. Mosnier JF, Perret AG, Vindimian M, et al. An immunohistochemical study of the simultaneous expression of bcl-2 and p53 oncoproteins in epithelial tumors of the colon and rectum. Arch Pathol Lab Med 1996;120:654–659.

    PubMed  CAS  Google Scholar 

  16. Hamana T, Kawai K, Serizawa A, et al. Immunohistochemical demonstration of p53 protein in colorectal adenomas and adenocarcinomas. Reliable application of the heat-induced antigen retrieval method to formalin-fixed, paraffin-embedded material. Pathol Int 1994;44:765–770.

    Article  PubMed  CAS  Google Scholar 

  17. Ohue M, Tomita N, Monden T, et al. A frequent alteration of p53 gene in carcinoma in adenoma of colon. Cancer Res 1994;54:4798–4804.

    PubMed  CAS  Google Scholar 

  18. Darmon E, Cleary KR, Wargovich MJ. Immunohistochemical analysis of p53 overexpression in human colonic tumors. Cancer Detect Prev 1994;18:187–195.

    PubMed  CAS  Google Scholar 

  19. Sheahan K, Shuja S, Murnane MJ. Cysteine protease activities and tumor development in human colorectal carcinoma. Cancer Res 1989;49:3809–3814.

    PubMed  CAS  Google Scholar 

  20. Tumminello FM, Gebbia N, Pizzolanti G, et al. Cathepsin D content in colorectal cancer. Correlation with cathepsin D activity and other biological parameters: a preliminary report. Oncology 1995;52:237–242.

    Article  PubMed  CAS  Google Scholar 

  21. Mayer A, Fritz E, Fortelny R, et al. Immunohistochemical evaluation of cathepsin D expression in colorectal cancer. Cancer Invest 1997;15:106–110.

    Article  PubMed  CAS  Google Scholar 

  22. Arao J, Fukui H, Ono Y, et al. Immunohistochemical localization of cathepsin D in colorectal tumors. Dis Colon Rectum 2000;43:396–401.

    Article  PubMed  CAS  Google Scholar 

  23. Harris GJ, Senagore AJ, Lavery IC, et al. Factors affecting survival after palliative resection of colorectal carcinoma. Colorectal Dis 2002;4:31–35.

    Article  PubMed  Google Scholar 

  24. Geraghty JM, Williams CB, Talbot IC. Malignant colorectal polyps: venous invasion and successful treatment by endoscopic polypectomy. Gut 1991;32:774–778.

    Article  PubMed  CAS  Google Scholar 

  25. Bertorelle R, Esposito G, Del Mistro A, et al. Association of p53 gene and protein alterations with metastases in colorectal cancer. Am J Surg Pathol 1995;19:463–471.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Pathology, Showa University School of Medicine, 5 Hatanodai-1, Shinagawa-ku, 142-8666, Tokyo, Japan

    Toshiaki Kunimura MD, Tomoko Inagaki, Masahiro Wada, Jun Ushio, Kasumi Sato, Tetsuji Enosawa, Masanao Nakashima, Hirotaka Kato, Ryouji Hayashi, Kouji Saitou & Toshio Morohoshi

Authors
  1. Toshiaki Kunimura MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomoko Inagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahiro Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Ushio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kasumi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tetsuji Enosawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masanao Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hirotaka Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ryouji Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kouji Saitou
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Toshio Morohoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshiaki Kunimura MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kunimura, T., Inagaki, T., Wada, M. et al. Immunohistochemical evaluation of tissue-specific proteolytic enzymes in adenomas containing foci of early carcinoma. Int J Gastrointest Canc 33, 149–154 (2003). https://doi.org/10.1385/IJGC:33:2-3:149

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/IJGC:33:2-3:149

Key Words

Search

Navigation