Skip to main content
SpringerLink
Log in

Lymphatic Tumor Emboli Detected by D2-40 Immunostaining Can More Accurately Predict Lymph-node Metastasis

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

Resected specimens of superficial squamous cell carcinoma of the esophagus (SSCCE) underwent D2-40 immunostaining to accurately assess lymphatic tumor emboli (LY) and to analyze correlations between LY and lymph node metastasis (N). This present study was designed to determine the accuracy of LY grade for predicting the risk of N.

Materials and methods

We studied 75 patients with SSCCE who underwent surgical resection of their tumors. Resected specimens were sliced into continuous sections at 5 mm intervals. Intramucosal cancers are classified into three groups (m1, m2, m3), and submucosal cancers are also divided into three groups (sm1, sm2, sm3). The numbers of LY present in lymphatic ducts on D2-40 immunostaining, venous tumor emboli (V) on CD34 immunostaining, and lymphatic tumor emboli (ly) and V on hematoxylin-eosin staining (HE) and elastica van Gieson staining (EVG) were counted for each case. The presence of lymphatic tumor emboli was graded according to the total number of LY per case as follows: 0, LY0; 1 to 2, LY1; 3 to 9, LY2; and 10 or more, LY3.

Results

All m1 and m2 cases were LY− and N− Lymphatic tumor emboli were present in 54% of m3 cases, 70% of sm1 cases, 54% of sm2 cases, and 75% of sm3 cases. Determination of N was positive in 18% of m3 cases, 47% of sm1 cases, 36% of sm2 cases, and 62% of sm3 cases. The frequency of LY significantly correlated with the number of N (p < 0.0001). Multiple regression analysis showed that only LY and V significantly correlated with N. When the detection rate of N was compared between LY and ly, LY was superior to ly in terms of specificity, accuracy, positive predictive value, and false positive rate. As for LY grade, N was positive in 39.1% of LY1 cases, 81.8% of LY2 cases, and 100% of LY3 cases. Even in LY-, N was positive in one sm1 case and in two sm2 cases. In the sm1 case, the depth of invasion was 350 μm from the lower margin of the muscularis mucosae.

Conclusions

Evaluation of lymphatic invasion on the basis of LY is more accurate for the prediction of N than conventional techniques, and LY grade strongly correlates with N. In patients with SSCCE, mucosal cancers (m1, m2, and m3) and submucosal cancers with a depth of invasion of ≤200 μm from the lower margin of the muscularis mucosae on endoscopic mucosal resection have a low risk of N if the number of LY is 0. Endoscopic mucosal resection alone can provide good treatment outcomes in such patients.

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

Similar content being viewed by others

References

  1. Endo M, Yoshino K, Kawano T et al (2000) Clinicopathologic analysis of lymph node metastasis in surgically resected superficial cancer of the thoracic esophagus. Dis Esophagus 13:125–129

    Article  PubMed  CAS  Google Scholar 

  2. Shimizu Y, Tsukagoshi H, Fujita M et al (2002) Long-term outcome after endoscopic mucosal resection in patients with esophageal squamous cell carcinoma invading the muscularis mucosae or deeper. Gastrointest Endosc 56:387–390

    Article  PubMed  Google Scholar 

  3. Mariette C, Piessen G, Triboulet JP (2007) Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 8:545–553

    Article  PubMed  Google Scholar 

  4. Shimada H, Nabeya Y, Matsubara H et al (2006) Prediction of lymph node status in patients with superficial esophageal carcinoma: analysis of 160 surgically resected cancers. Am J Surg 191:250–254

    Article  PubMed  Google Scholar 

  5. Japanese Classification of Esophageal Cancer, Japan Esophageal Society (2008) Kanehara & Co., Ltd, Tokyo

  6. Kuwano H, Nishimura Y, Ohtsu A, for the Japan Esophageal Society et al (2008) Guidelines for diagnosis and treatment of carcinoma of the esophagus, April 2007 edition: part I. Esophagus 5:61–73

    Article  Google Scholar 

  7. Eguchi T, Nakanishi Y, Shimoda T et al (2006) Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases. Mod Pathol 19:475–480

    Article  PubMed  Google Scholar 

  8. Tajima Y, Nakanishi Y, Ochiai A et al (2000) Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma: analysis of 240 surgically resected tumors. Cancer 15(88):1285–1293

    Article  Google Scholar 

  9. Yonemura Y, Endou Y, Tabachi K et al (2006) Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40. Hum Pathol 37:1193–1199

    Article  PubMed  CAS  Google Scholar 

  10. Acs G, Dumoff KL, Solin LJ et al (2007) Extensive retraction artifact correlates with lymphatic invasion and nodal metastasis and predicts poor outcome in early stage breast carcinoma. Am J Surg Pathol 31:129–140

    Article  PubMed  Google Scholar 

  11. Kahn HJ, Bailey P, Marks A (2002) Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol 15:434–440

    Article  PubMed  Google Scholar 

  12. Cursiefen C, Schlötzer-Schrehardt U, Küchle M et al (2002) Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin. Invest Ophthalmol Vis Sci 43:2127–2135

    PubMed  Google Scholar 

  13. Alessandro F, Oreste G, Daniela M et al (2004) Tumor lymphangiogenesis in head and neck squamous cell carcinoma. Cancer 10:973–978

    Google Scholar 

  14. Franchi A, Gallo O, Massi D et al (2004) Tumor lymphangiogenesis in head and neck squamous cell carcinoma: a morphometric study with clinical correlations. Cancer 101:973–978

    Article  PubMed  Google Scholar 

  15. Niakosari F, Kahn HJ, Marks A et al (2005) Detection of lymphatic invasion in primary melanoma with monoclonal antibody D2-40: a new selective immunohistochemical marker of lymphatic endothelium. Arch Dermatol 141:440–444

    Article  PubMed  Google Scholar 

  16. Fukunaga M (2005) Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology 46:396–402

    Article  PubMed  CAS  Google Scholar 

  17. Evangelou E, Kyzas PA, Trikalinos TA (2005) Comparison of the diagnostic accuracy of lymphatic endothelium markers: Bayesian approach. Mod Pathol 18:1490–1497

    Article  PubMed  CAS  Google Scholar 

  18. Yamauchi C, Hasebe T, Iwasaki M et al (2007) Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance. Hum Pathol 38:247–259

    Article  PubMed  Google Scholar 

  19. Japanese Society for Esophageal Diseases (2004) Guidelines for clinical and pathological studies on carcinoma of the esophagus, ninth edition, preface, general principles, part I. Esophagus 1:61–88

    Google Scholar 

  20. Mori D, Yamasaki F, Shibaki M et al (2007) Lateral peritumoral lymphatic vessel invasion can predict lymph node metastasis in esophageal squamous cell carcinoma. Mod Pathol 20:694–700

    Article  PubMed  Google Scholar 

  21. Mizowaki T, Nishimura Y, Shimada Y et al (1996) Optimal size criteria of malignant lymph nodes in the treatment planning of radiotherapy for esophageal cancer: evaluation by computed tomography and magnetic resonance imaging. Int J Radiat Oncol Biol Phys 36:1091–1098

    Article  PubMed  CAS  Google Scholar 

  22. Kato H, Kuwano H, Nakajima M et al (2002) Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma. Cancer 94:921–928

    Article  PubMed  Google Scholar 

  23. Murata Y, Ohta M, Hayashi K et al (2003) Preoperative evaluation of lymph node metastasis in esophageal cancer. Ann Thorac Cardiovasc Surg 9:88–92

    PubMed  Google Scholar 

  24. Kajiyama Y, Iwanuma Y, Tomita N et al (2006) Size analysis of lymph node metastasis in esophageal cancer: diameter distribution and assessment of accuracy of preoperative diagnosis. Esophagus 3:189–195

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, School of Medicine, Kitasato University, Tokyo, Japan

    Hiromitsu Moriya, Nobuyuki Kobayashi, Natsuya Katada, Nobue Futawatari, Shinichi Sakuramoto, Shiro Kikuchi & Masahiko Watanabe

  2. Department of Pathology, School of Allied Health Sciences, Kitasato University, Tokyo, Japan

    Makoto Ohbu

  3. Department of Internal Medicine, School of Medicine, Kitasato University, Tokyo, Japan

    Satoshi Tanabe

  4. Department of Pathology, School of Medicine, Kitasato University, Tokyo, Japan

    Isao Okayasu

Authors
  1. Hiromitsu Moriya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Makoto Ohbu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nobuyuki Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoshi Tanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Natsuya Katada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nobue Futawatari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shinichi Sakuramoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shiro Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Isao Okayasu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masahiko Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiromitsu Moriya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moriya, H., Ohbu, M., Kobayashi, N. et al. Lymphatic Tumor Emboli Detected by D2-40 Immunostaining Can More Accurately Predict Lymph-node Metastasis. World J Surg 35, 2031–2037 (2011). https://doi.org/10.1007/s00268-011-1143-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-011-1143-2

Keywords

Search

Navigation