Skip to main content

Advertisement

SpringerLink
Log in

Different apoptotic activity and p21WAF1/CIP1, but not p27Kip1, expression in serrated adenomas as compared with traditional adenomas and hyperplastic polyps of the colorectum

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Serrated adenomas (SAs), which include a wide spectrum of lesions, can be broadly divided into two subtypes: type I, closely mimicking hyperplastic polyps (HPs), and type II, unequivocal adenomatous tumor. Our preliminary findings showed clinicopathologic differences between them. The present study was conducted to investigate apoptotic activity and expression of the cell cycle regulator proteins p21WAF1/CIP1 and p27Kip1 in type I and II SAs, as compared with traditional adenomas (TAs) and HPs.

Methods

Apoptotic activity was estimated in hematoxylin-eosin stained specimens, and p21WAF1/CIP1 or p27Kip1 immunoreactivity was determined in 62 SAs (19 type I and 43 type II), 50 TAs and 19 HPs. The numbers (percentages) of apoptotic or immunoreactive cells were counted per 1,000 epithelial cells in equally separated crypt zones (upper, middle, and lower thirds).

Results

The apoptotic activity in the middle, but not the upper or lower crypt zone was higher in type II SAs (median 0.2%, interquartile range 0.1–0.5%) than in HPs (0.1%, 0.1–0.2%, P<0.01), whereas it was lower in type I SAs (0.2%, 0.1–0.3%) than in TAs (0.5%, 0.2–0.6%, P<0.001). P21WAF1/CIP1 expression in the lower crypt zone was higher in both type I and type II SAs (19.8%, 7.0–33.2% and 20.4%, 3.9–47.8%, P<0.0001) than in TAs (1.2%, 0.6–5.2%), and a similar tendency was also observed for the middle crypt zone. p27Kip1 expression did not vary among the groups.

Conclusions

The differences in apoptotic activity and p21WAF1/CIP1 expression between SAs and TAs or HPs indicate that SA should be considered as a distinct subtype of colorectal neoplasm. The two subtypes of SA do not differ in these parameters despite specific clinicopathological features.

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

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6A–C.

Similar content being viewed by others

References

  • Ajioka Y, Watanabe H, Jass JR, Yokota Y, Kobayashi M, Nishikura K (1998) Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum. Gut 42:680–684

    PubMed  Google Scholar 

  • Akino F, Mitomi H, Nakamura T, Ohtani Y, Ichinoe M, Okayasu I (2002) High apoptotic activity and low epithelial cell proliferation with underexpression of p21WAF1/CIP1 and p27Kip1 of mucinous carcinomas of the colorectum. Comparison with well-differentiated type. Am J Clin Pathol 117:908–915

    PubMed  Google Scholar 

  • Ansari B, Coates PJ, Greenstein BD, Hall PA (1993) In situ end-labelling detects DNA strand breaks in apoptosis and other physiological and pathological states. J Pathol 170:1–8

    CAS  PubMed  Google Scholar 

  • Ban S (1999) Small hyperplastic polyps of the colorectum showing deranged cell organization: a lesion considered to be a serrated adenoma? Am J Surg Pathol 23:1158–1160

    Google Scholar 

  • Ciaparrone M, Yamamoto H, Yao Y, Sgambato A, Cattoretti G, Tomita N, Monden T, Rotterdam H, Weinstein IB (1998) Localization and expression of p27KIP1 in multistage colorectal carcinogenesis. Cancer Res 58:114–122

    PubMed  Google Scholar 

  • Cordon-Cardo C (1995) Mutation of cell cycle regulators. Biological and clinical implications for human neoplasia. Am J Pathol 147:545–560

    PubMed  Google Scholar 

  • Doglioni C, Pelosio P, Laurino L, Macri E, Meggiolaro E, Favretti F, Barbareschi M (1996) p21/waf1/cip1 expression in normal mucosa and in adenomas and adenocarcinomas of the colon: its relationship with differentiation. J Pathol 179:248–253

    Article  PubMed  Google Scholar 

  • Frankfurt OS, Robb JA, Sugarbaker EV, Villa L (1996) Monoclonal antibody to single-stranded DNA is a specific and sensitive cellular marker of apoptosis. Exp Cell Res 226:387–397

    Article  CAS  PubMed  Google Scholar 

  • Fujishima N (1996) Proliferative activity of mixed hyperplastic adenomatous polyp/serrated adenoma in the large intestine, measured by PCNA (proliferating cell nuclear antigen). J Gastroenterol 31:207–213

    PubMed  Google Scholar 

  • Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501

    CAS  PubMed  Google Scholar 

  • Hiyama T, Yokozaki H, Shimamoto F, Haruma K, Yasui W, Kajiyama G, Tahara E (1998) Frequent p53 gene mutations in serrated adenomas of the colorectum. J Pathol 186:131–139

    Article  CAS  PubMed  Google Scholar 

  • Jaramillo E, Watanabe M, Rubio C, Slezak P (1996) Small colorectal serrated adenomas: endoscopic findings. Endoscopy 28:1–3

    PubMed  Google Scholar 

  • Jass JR, Sobin LH (1989). WHO histological typing of intestinal tumours, 2nd edn. Springer, Berlin Heidelberg New York

  • Kang M, Mitomi H, Sada M, Tokumitsu Y, Takahashi Y, Igarashi M, Katsumata T, Okayasu I (1997) Ki-67, p53, and Bcl-2 expression of serrated adenomas of the colon. Am J Surg Pathol 21:417–423

    Article  PubMed  Google Scholar 

  • Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    PubMed  Google Scholar 

  • Kobayashi T, Consoli U, Andreeff M, Shiku H, Deisseroth AB, Zhang W (1995) Activation of p21WAF1/Cip1 expression by a temperature-sensitive mutant of human p53 does not lead to apoptosis. Oncogene 11:2311–2316

    CAS  PubMed  Google Scholar 

  • Levine DS, Haggitt RC (1992) Colon. In: Sternberg SS, ed. Histology for pathologists. Raven Press, New York

  • Longacre TA, Fenoglio-Preiser CM (1990) Mixed hyperplastic adenomatous polyp/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol 14:524–537

    CAS  PubMed  Google Scholar 

  • Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T (1995) p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev 9:935–944

    CAS  PubMed  Google Scholar 

  • Matsumoto T, Mizuno M, Shimizu M, Manabe T, Iida M (1999a) Clinicopathological features of serrated adenoma of the colorectum: comparison with traditional adenoma. J Clin Pathol 52:513–516

    PubMed  Google Scholar 

  • Matsumoto T, Mizuno M, Shimizu M, Manabe T, Iida M, Fujishima M (1999b) Serrated adenoma of the colorectum: colonoscopic and histologic features. Gastrointest Endosc 49:736–742

    PubMed  Google Scholar 

  • Michieli P, Chedid M, Lin D, Pierce JH, Mercer WE, Givol D (1994) Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res 54:3391–3395

    CAS  PubMed  Google Scholar 

  • Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ (1995) p53-independent expression of p21cip1 in muscle and other terminally differentiating cells. Science 267:1024–1027

    CAS  PubMed  Google Scholar 

  • Polyak K, Kato J, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A (1994) p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-β and contact inhibition to cell cycle arrest. Genes Dev 8:9–22.

    CAS  PubMed  Google Scholar 

  • Rubio CA, Jaramillo E (1996) Flat serrated adenomas of the colorectal mucosa. Jpn J Cancer Res 87:305–309

    PubMed  Google Scholar 

  • Rubio CA, Rodensjö M (1995a) Flat serrated adenomas and flat tubular adenomas of the colorectal mucosa: differences in the pattern of cell proliferation. Jpn J Cancer Res 86:756–760

    PubMed  Google Scholar 

  • Rubio CA, Rodensjö M (1995b) p53 overexpression in flat serrated adenomas and flat tubular adenomas of the colorectal mucosa. J Cancer Res Clin Oncol 121:571–576

    PubMed  Google Scholar 

  • Sasaki K, Sato T, Kurose A, Ikeda E (1996) Immunohistochemical detection of p21waf1/cip1/sdi1 and p53 proteins in formalin-fixed, paraffin-embedded tissue sections of colorectal carcinoma. Hum Pathol 27:912–916

    CAS  PubMed  Google Scholar 

  • Sinicrope FA, Roddey G, Lemoine M, Ruan S, Stephens LC, Frazier ML, Shen Y, Zhang W (1998) Loss of p21WAF1/Cip1 protein expression accompanies progression of sporadic colorectal neoplasms but not hereditary nonpolyposis colorectal cancers. Clin Cancer Res 4:1251–1261

    CAS  PubMed  Google Scholar 

  • Strater J, Koretz K, Gunthert AR, Moller P (1995) In situ detection of enterocytic apoptosis in normal colonic mucosa and in familial adenomatous polyposis. Gut 37:819–825

    PubMed  Google Scholar 

  • Tateyama H, Li W, Takahashi E, Miura Y, Sugiura H, Eimoto T (2002) Apoptosis index and apoptosis-related antigen expression in serrated adenoma of the colorectum. The saw-toothed structure may be related to inhibition of apoptosis. Am J Surg Pathol 26:249–256

    Article  PubMed  Google Scholar 

  • Torlakovic E, Snover DC (1996) Serrated adenomatous polyposis in humans. Gastroenterology 110:748–755

    CAS  PubMed  Google Scholar 

  • Viale G, Pellegrini C, Mazzarol G, Maisonneuve P, Silverman ML, Bosari S (1999) p21WAF1/CIP1 expression in colorectal carcinoma correlates with advanced disease stage and p53 mutations. J Pathol 187:302–307

    Article  CAS  PubMed  Google Scholar 

  • Yao T, Kouzuki T, Kajiwara M, Matsui N, Oya M, Tsuneyoshi M (1999) 'Serrated adenoma' of the colorectum, with reference to its gastric differentiation and its malignant potential. J Pathol 187:511–517

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank H. Shinoda, K. Yamashita, M. Yokozawa, K. Kubokawa, I. Yokoyama, T. Tatebayashi, T. Kuba, S. Yoshida, and T. Takahashi, Kitasato University East Hospital, for their expert technical assistance.

This work is supported in part by Health and Labour Sciences Research Grants for Research on Allergic Diseases and Immunology (A.M.).

Author information

Authors and Affiliations

  1. Department of Pathology, National Sagamihara Hospital, 18-1 Sakura-dai, 228-8522, Sagamihara, Kanagawa, Japan

    Hiroyuki Mitomi

  2. Department of Internal Medicine, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan

    Miwa Sada, Kiyonori Kobayashi & Masahiro Igarashi

  3. Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa, Japan

    Akio Mori

  4. Department of Surgery, National Sagamihara Hospital, Sagamihara, Kanagawa, Japan

    Hideki Kanazawa & Yasuhiko Nishiyama

  5. Department of Surgery, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan

    Atsushi Ihara & Yoshimasa Otani

Authors
  1. Hiroyuki Mitomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miwa Sada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiyonori Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masahiro Igarashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akio Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideki Kanazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuhiko Nishiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Atsushi Ihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshimasa Otani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Mitomi.

Additional information

Drs. Mitomi and Sada contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitomi, H., Sada, M., Kobayashi, K. et al. Different apoptotic activity and p21WAF1/CIP1, but not p27Kip1, expression in serrated adenomas as compared with traditional adenomas and hyperplastic polyps of the colorectum. J Cancer Res Clin Oncol 129, 449–455 (2003). https://doi.org/10.1007/s00432-003-0478-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-003-0478-y

Keywords

Search

Navigation