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Borrmann’s Macroscopic Criteria and p-Smad2 Expression Are Useful Predictive Prognostic Markers for Cytology-Positive Gastric Cancer Patients Without Overt Peritoneal Metastasis

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

All patients with peritoneal-free cancer cells (CY1) do not always develop a peritoneal recurrence (P1). The goal of this study was to identify characteristic features of peritoneal-free cancer cells that could develop into peritoneal recurrence.

Methods

Of 1,474 patients, 91 were identified with CY1P0, and the remaining 1,383 with CY0P0. Immunohistochemical staining with anti-phosphorylated Smad 2 (p-Smad2) was performed on paraffin-embedded specimens from the 91 CY1P0 patients.

Results

CY1 was significantly correlated with Borrmann’s type-4 cancer, clinical T stage, and lymph node metastasis. CY1P0 patients with Borrmann’s type-4 cancer more frequently develop peritoneal recurrence than do those with other types of tumors. The 5-year survival rate of patients with Borrmann’s type-4 tumors was significantly (p = 0.023) low (6.3%) compared with that of patients with other types of tumors (27.7%). The prognosis for p-Smad2-positive patients was significantly poorer than that of p-Smad2-negative patients. In CY1 and/or P1 patients with Borrmann’s type-4 tumors, no significant difference in prognosis was identified between those who had surgery and those who did not.

Conclusions

Activated Smad signaling might be associated with a high potential for peritoneal recurrence in CY1P0 patients. Borrmann’s macroscopic criteria and p-Smad2 expression are useful markers for surgeons selecting advanced gastric cancer patients with CY1P0 for gastrectomy.

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References

  1. Maehara Y, Hasuda S, Koga T, Tokunaga E, Kakeji Y, Sugimachi K. Postoperative outcome and sites of recurrence in patients following curative resection of gastric cancer. Br J Surg. 2000;87:353–7.

    Article  PubMed  CAS  Google Scholar 

  2. Hiratsuka M, Iwanaga T, Furukawa H, Yasuda T, Nakano H, Nakamori S, Ohigashi H, Kameyama M, Sasaki Y, Kabuto T, et al. Important prognostic factors in surgically treated gastric cancer patients. Gan To Kagaku Ryoho. 1995;22:703–8.

    PubMed  CAS  Google Scholar 

  3. Nishimura S, Chung YS, Yashiro M, Inoue T, Sowa M. Role of alpha 2 beta 1- and alpha 3 beta 1-integrin in the peritoneal implantation of scirrhous gastric carcinoma. Br J Cancer. 1996;74:1406–12.

    Article  PubMed  CAS  Google Scholar 

  4. Yashiro M, Chung YS, Nishimura S, Inoue T, Sowa M. Establishment of two new scirrhous gastric cancer cell lines: analysis of factors associated with disseminated metastasis. Br J Cancer. 1995;72:1200–10.

    Article  PubMed  CAS  Google Scholar 

  5. Japanese Gastric Cancer. Japanese classification of gastric carcinoma, 2nd English edn. Gastric Cancer. 1998;1:10–24.

    Article  Google Scholar 

  6. Burke EC, Karpeh Jr MS, Conlon KC, Brennan MF. Peritoneal lavage cytology in gastric cancer: an independent predictor of outcome. Ann Surg Oncol. 1998;5:411–5.

    Article  PubMed  CAS  Google Scholar 

  7. Nath J, Moorthy K, Taniere P, Hallissey M, Alderson D. Peritoneal lavage cytology in patients with oesophagogastric adenocarcinoma. Br J Surg. 2008;95:721–6.

    Article  PubMed  CAS  Google Scholar 

  8. Yamamoto M, Matsuyama A, Kameyama T, Okamoto M, Okazaki J, Utsunomiya T, Tsutsui S, Fujiwara M, Ishida T. Prognostic re-evaluation of peritoneal lavage cytology in Japanese patients with gastric carcinoma. Hepatogastroenterology. 2009;56:261–5.

    PubMed  Google Scholar 

  9. Miyashiro I, Takachi K, Doki Y, Ishikawa O, Ohigashi H, Murata K, Sasaki Y, Imaoka S, Nakaizumi A, Takenaka A, Furukawa H, Hiratsuka M. When is curative gastrectomy justified for gastric cancer with positive peritoneal lavage cytology but negative macroscopic peritoneal implant? World J Surg. 2005;29:1131–4.

    Article  PubMed  Google Scholar 

  10. Fu H, Hu Z, Wen J, Wang K, Liu Y. TGF-beta promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways. Acta Biochim Biophys Sin (Shanghai). 2009;41:648–56.

    Article  CAS  Google Scholar 

  11. Inoue T, Chung YS, Yashiro M, Nishimura S, Hasuma T, Otani S, Sowa M. Transforming growth factor-beta and hepatocyte growth factor produced by gastric fibroblasts stimulate the invasiveness of scirrhous gastric cancer cells. Jpn J Cancer Res. 1997;88:152–9.

    Article  PubMed  CAS  Google Scholar 

  12. Tsuji T, Kawada Y, Kai-Murozono M, Komatsu S, Han SA, Takeuchi K, Mizushima H, Miyazaki K, Irimura T. Regulation of melanoma cell migration and invasion by laminin-5 and alpha3beta1 integrin (VLA-3). Clin Exp Metastasis. 2002;19:127–34.

    Article  PubMed  CAS  Google Scholar 

  13. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 2001;29:117–29.

    Article  PubMed  CAS  Google Scholar 

  14. Miyazono K, Suzuki H, Imamura T. Regulation of TGF-beta signaling and its roles in progression of tumors. Cancer Sci. 2003;94:230–4.

    Article  PubMed  CAS  Google Scholar 

  15. Kizaka-Kondoh S, Itasaka S, Zeng L, Tanaka S, Zhao T, Takahashi Y, Shibuya K, Hirota K, Semenza GL, Hiraoka M. Selective killing of hypoxia-inducible factor-1-active cells improves survival in a mouse model of invasive and metastatic pancreatic cancer. Clin Cancer Res. 2009;15:3433–41.

    Article  PubMed  CAS  Google Scholar 

  16. Cao Z, Flanders KC, Bertolette D, Lyakh LA, Wurthner JU, Parks WT, Letterio JJ, Ruscetti FW, Roberts AB. Levels of phospho-Smad2/3 are sensors of the interplay between effects of TGF-beta and retinoic acid on monocytic and granulocytic differentiation of HL-60 cells. Blood. 2003;101:498–507.

    Article  PubMed  CAS  Google Scholar 

  17. Feng XH, Derynck R. Specificity and versatility in TGF-beta signaling through Smads. Annu Rev Cell Dev Biol. 2005;21:659–93.

    Article  PubMed  CAS  Google Scholar 

  18. Kawajiri H, Yashiro M, Shinto O, Nakamura K, Tendo M, Takemura S, Node M, Hamashima Y, Kajimoto T, Sawada T, Ohira M, Hirakawa K. A novel transforming growth factor beta receptor kinase inhibitor, A-77, prevents the peritoneal dissemination of scirrhous gastric carcinoma. Clin Cancer Res. 2008;14:2850–60.

    Article  PubMed  CAS  Google Scholar 

  19. Takatsuki H, Komatsu S, Sano R, Takada Y, Tsuji T. Adhesion of gastric carcinoma cells to peritoneum mediated by alpha3beta1 integrin (VLA-3). Cancer Res. 2004;64:6065–70.

    Article  PubMed  CAS  Google Scholar 

  20. Sobin LH. TNM, 6th edn: new developments in general concepts and rules. Semin Surg Oncol. 2003;21:19–22.

    Article  PubMed  Google Scholar 

  21. Ishibashi H, Suzuki T, Suzuki S, Moriya T, Kaneko C, Takizawa T, Sunamori M, Handa M, Kondo T, Sasano H. Sex steroid hormone receptors in human thymoma. J Clin Endocrinol Metab. 2003;88:2309–17.

    Article  PubMed  CAS  Google Scholar 

  22. Shinto O, Yashiro M, Kawajiri H, Shimizu K, Shimizu T, Miwa A, Hirakawa K. Inhibitory effect of a TGFbeta receptor type-I inhibitor, Ki26894, on invasiveness of scirrhous gastric cancer cells. Br J Cancer. 2010;102:844–51.

    Article  PubMed  CAS  Google Scholar 

  23. Noda S, Yashiro M, Nshii T, Hirakawa K. Hypoxia upregulates adhesion ability to peritoneum through a transforming growth factor-beta-dependent mechanism in diffuse-type gastric cancer cells. Eur J Cancer. 2010;46:995–1005.

    Article  PubMed  CAS  Google Scholar 

  24. Wu CC, Chen JT, Chang MC, Ho ML, Chen CY, Yeh DC, Liu TJ, P’Eng KF. Optimal surgical strategy for potentially curable serosa-involved gastric carcinoma with intraperitoneal free cancer cells. J Am Coll Surg. 1997;184:611–7.

    PubMed  CAS  Google Scholar 

  25. Ikeguchi M, Miyake T, Matsunaga T, Yamamoto M, Fukumoto Y, Yamada Y, Fukuda K, Saito H, Tatebe S, Tsujitani S. Recent results of therapy for scirrhous gastric cancer. Surg Today. 2009;39:290–4.

    Article  PubMed  CAS  Google Scholar 

  26. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.

    PubMed  CAS  Google Scholar 

  27. Hara M, Nakanishi H, Jun Q, Kanemitsu Y, Ito S, Mochizuki Y, Yamamura Y, Kodera Y, Tatematsu M, Hirai T, Kato T. Comparative analysis of intraperitoneal minimal free cancer cells between colorectal and gastric cancer patients using quantitative RT-PCR: possible reason for rare peritoneal recurrence in colorectal cancer. Clin Exp Metastasis. 2007;24:179–89.

    Article  PubMed  Google Scholar 

  28. Vogel P, Ruschoff J, Kummel S, Zirngibl H, Hofstadter F, Hohenberger W, Jauch KW. Prognostic value of microscopic peritoneal dissemination: comparison between colon and gastric cancer. Dis Colon Rectum. 2000;43:92–100.

    Article  PubMed  CAS  Google Scholar 

  29. Luebke T, Baldus SE, Grass G, Bollschweiler E, Thiele J, Dienes HP, Hoelscher AH, Moenig SP. Histological grading in gastric cancer by Ming classification: correlation with histopathological subtypes, metastasis, and prognosis. World J Surg. 2005;29:1422–7.

    Article  PubMed  Google Scholar 

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Conflict of interest

The all of authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Satoru Noda, Masakazu Yashiro, Takahiro Toyokawa, Jyunya Morimoto, Osamu Shinto, Kazuya Muguruma, Tetsuji Sawada & Kosei Hirakawa

  2. Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Osaka, Japan

    Masakazu Yashiro

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  1. Satoru Noda
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  2. Masakazu Yashiro
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  3. Takahiro Toyokawa
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  4. Jyunya Morimoto
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Correspondence to Masakazu Yashiro.

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Noda, S., Yashiro, M., Toyokawa, T. et al. Borrmann’s Macroscopic Criteria and p-Smad2 Expression Are Useful Predictive Prognostic Markers for Cytology-Positive Gastric Cancer Patients Without Overt Peritoneal Metastasis. Ann Surg Oncol 18, 3718–3725 (2011). https://doi.org/10.1245/s10434-011-1768-2

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  • DOI: https://doi.org/10.1245/s10434-011-1768-2

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