Abstract
Background
Among various clinical and pathological findings, lymphatic invasion (Ly) is the strongest risk factor for nodal metastasis in gastric cancer. However, the diagnosis of Ly is subjective and often inaccurate because of the difficulty of detecting lymphatic vessels with conventional hematoxylin and eosin (HE) staining.
Methods
The distribution of lymphatics in the normal gastric wall was immunohistochemically characterized using a new selective marker of lymphatic endothelium, D2-40, in surgical specimens resected for early gastric cancer (EGC). Then, Ly in the primary lesion was reevaluated, and the positive (PPV) and negative (NPV) predictive values for nodal metastasis were comparatively examined for Ly detected by HE staining (Ly-HE) and by immunohistochemical staining (Ly-IM) in 131 cases of EGC.
Results
D2-40-positive lymphatic vessels were observed in the deep proper mucosal layer, and the lymphatic vessel density (LVD) was extremely high in the muscularis mucosa (MM) layer. The number of Ly-IM-positive cases (15/131) was higher than the Ly-HE-positive cases (10/131). In 48 cases of intestinal-type cancer, Ly-IM had a PPV of 33.3% (2/6) and anNPV of 100% (42/42), which was more accurate than the corresponding figures for Ly-HE (25% and 98%, respectively). In contrast, the accuracy of Ly-IM was similar to that of Ly-HE in 83 cases of diffuse-type cancer.
Conclusion
Lymphatic vessels are most densely distributed in the MM layer in the gastric wall. Immunohistochemical identification of lymphatics is useful to increase the accuracy of diagnosing Ly in resected gastric EGCs. Ly-IM is superior to Ly-HE as a predictor of nodal metastasis, at least for intestinal-type EGC.
Article PDF
Similar content being viewed by others
References
T Sano M Sasako T Kinoshita K Maruyama (1993) ArticleTitleRecurrence of early gastric cancer: follow-up of 1475 patients and review of the Japanese literature Cancer 72 3174–8 Occurrence Handle8242540 Occurrence Handle1:STN:280:ByuD287nsVE%3D Occurrence Handle10.1002/1097-0142(19931201)72:11<3174::AID-CNCR2820721107>3.0.CO;2-H
HM Sue-Ling I Martin J Griffith DC Ward P Quirke MF Dixon et al. (1992) ArticleTitleEarly gastric cancer: 46 cases treated in one surgical department Gut 33 1318–22 Occurrence Handle1446852 Occurrence Handle1:STN:280:ByyD2sjgvVc%3D
S Miyamoto M Muto Y Hamamoto N Boku A Ohtsu S Baba et al. (2002) ArticleTitleA new technique for endoscopic mucosal resection with an insulated-tip electrosurgical knife improves the completeness of resection of intramucosal gastric neoplasms Gastrointest Endosc 55 576–81 Occurrence Handle11923778 Occurrence Handle10.1067/mge.2002.122579
M Ohkuwa K Hosokawa N Boku A Ohtu H Tajiri S Yoshida (2001) ArticleTitleNew endoscopic treatment for intramucosal gastric tumors using an insulated-tip diathermic knife Endoscopy 33 221–6 Occurrence Handle11293753 Occurrence Handle1:STN:280:DC%2BD3Mvit1ChtQ%3D%3D Occurrence Handle10.1055/s-2001-12805
T Gotoda A Yanagisawa M Sasako H Ono Y Nakanishi T Shimoda et al. (2000) ArticleTitleIncidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers Gastric Cancer 3 219–25 Occurrence Handle11984739 Occurrence Handle10.1007/PL00011720
Y Maehara H Orita T Okuyama S Moriguchi S Tsujitani D Korenaga et al. (1992) ArticleTitlePredictors of lymph node metastasis in early gastric cancer Br J Surg 79 245–7 Occurrence Handle1555092 Occurrence Handle1:STN:280:By2B3cfnt1U%3D
T Yamao K Shirao H Ono H Kondo D Saito H Yamaguchi et al. (1996) ArticleTitleRisk factors for lymph node metastasis from intramucosal gastric carcinoma Cancer 77 602–6 Occurrence Handle8616749 Occurrence Handle1:STN:280:BymC1cnosVU%3D Occurrence Handle10.1002/(SICI)1097-0142(19960215)77:4<602::AID-CNCR3>3.0.CO;2-I
T Gotoda M Sasako H Ono H Katai T Sano T Shimoda (2001) ArticleTitleEvaluation of the necessity for gastrectomy with lymph node dissection for patients with submucosal invasive gastric cancer Br J Surg 88 444–9 Occurrence Handle11260114 Occurrence Handle1:STN:280:DC%2BD3M7msVyhsw%3D%3D Occurrence Handle10.1046/j.1365-2168.2001.01725.x
SY Song S Park S Kim HJ Son JC Rhee (2004) ArticleTitleCharacteristics of intramucosal gastric carcinoma with lymph node metastatic disease Histopathology 44 437–44 Occurrence Handle15139991 Occurrence Handle1:STN:280:DC%2BD2c3ktF2rtw%3D%3D Occurrence Handle10.1111/j.1365-2559.2004.01870.x
HJ Son SY Song S Kim JH Noh TS Sohn DS Kim et al. (2005) ArticleTitleCharacteristics of submucosal gastric carcinoma with lymph node metastatic disease Histopathology 46 158–65 Occurrence Handle15693888 Occurrence Handle1:STN:280:DC%2BD2M%2Fms1Wksw%3D%3D Occurrence Handle10.1111/j.1365-2559.2005.02049.x
S Breiteneder-Geleff A Soleiman H Kowalski R Horvat G Amann E Kriehuber et al. (1999) ArticleTitleAngiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium Am J Pathol 154 385–94 Occurrence Handle10027397 Occurrence Handle1:STN:280:DyaK1M7kvFKnsQ%3D%3D
JT Wigle G Oliver (1999) ArticleTitleProx1 function is required for the development of The murine lymphatic system Cell 98 769–78 Occurrence Handle10499794 Occurrence Handle1:CAS:528:DyaK1MXmt1Grs70%3D Occurrence Handle10.1016/S0092-8674(00)81511-1
S Banerji J Ni SX Wang S Clasper J Su R Tammi et al. (1999) ArticleTitleLYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan J Cell Biol 144 789–801 Occurrence Handle10037799 Occurrence Handle1:CAS:528:DyaK1MXhvVWmsLc%3D Occurrence Handle10.1083/jcb.144.4.789
N Ebata Y Nodasaka Y Sawa Y Yamaoka S Makino Y Totsuka et al. (2001) ArticleTitleDesmoplakin as a specific marker of lymphatic vessels Microvasc Res 61 40–8 Occurrence Handle11162194 Occurrence Handle1:STN:280:DC%2BD3MzptlektQ%3D%3D Occurrence Handle10.1006/mvre.2000.2280
A Kaipainen J Korhonen T Mustonen VW Van Hinsbergh GH Fang D Dumont et al. (1995) ArticleTitleExpression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development Proc Natl Acad Sci U S A 92 3566–70 Occurrence Handle7724599 Occurrence Handle1:CAS:528:DyaK2MXltFSmsLg%3D Occurrence Handle10.1073/pnas.92.8.3566
V Joukov K Pajusola A Kaipainen D Chilov I Lahtinen E Kukk et al. (1996) ArticleTitleA novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases EMBO J 15 290–98 Occurrence Handle8617204 Occurrence Handle1:CAS:528:DyaK28XovFSktA%3D%3D
CA Makin LG Bobrow WF Bodmer (1984) ArticleTitleMonoclonal antibody to cytokeratin for use in routine histopathology J Clin Pathol 37 975–83 Occurrence Handle6206100 Occurrence Handle1:STN:280:BiuB1M%2FgsFU%3D
HJ Kahn A Marks (2002) ArticleTitleA new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors Lab Invest 82 1255–7 Occurrence Handle12218087
InstitutionalAuthorNameJapanese Gastric Cancer Association (1998) ArticleTitleJapanese Classification of Gastric Carcinoma — 2nd English Edition Gastric Cancer 1 10–24 Occurrence Handle11957040 Occurrence Handle10.1007/PL00011681
HJ Kahn D Bailey A Marks (2002) ArticleTitleMonoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas Mod Pathol 15 434–40 Occurrence Handle11950918 Occurrence Handle10.1038/modpathol.3880543
A Marks DR Sutherland D Bailey J Iglesias J Law M Lei et al. (1999) ArticleTitleCharacterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours Br J Cancer 80 569–78 Occurrence Handle10408868 Occurrence Handle1:CAS:528:DyaK1MXjtFyks7w%3D Occurrence Handle10.1038/sj.bjc.6690393
A Franchi O Gallo D Massi G Baroni M Santucci (2004) ArticleTitleTumor lymphangiogenesis in head and neck squamous cell carcinoma: a morphometric study with clinical correlations Cancer 101 973–8 Occurrence Handle15329906 Occurrence Handle10.1002/cncr.20454
F Niakosari HJ Kahn A Marks L From (2005) ArticleTitleDetection of lymphatic invasion in primary melanoma with monoclonal antibody D2-40: a new selective immunohistochemical marker of lymphatic endothelium Arch Dermatol 141 440–4 Occurrence Handle15837861 Occurrence Handle10.1001/archderm.141.4.440
F Fogt RL Zimmerman HM Ross T Daly RE Gausas (2004) ArticleTitleIdentification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40 Oncol Rep 11 47–50 Occurrence Handle14654901 Occurrence Handle1:CAS:528:DC%2BD2cXjt1ajug%3D%3D
T Lehnert RA Erlandson JJ Decosse (1985) ArticleTitleLymph and blood capillaries of the human gastric mucosa: a morphologic basis for metastasis in early gastric carcinoma Gastroenterology 89 939–50 Occurrence Handle4043674 Occurrence Handle1:STN:280:BimD3cnhsFw%3D
MB Listrom CM Fenoglio-Preiser (1987) ArticleTitleLymphatic distribution of the stomach in normal, inflammatory, hyperplastic, and neoplastic tissue Gastroenterology 93 506–14 Occurrence Handle3301516 Occurrence Handle1:STN:280:BiiB2sjitlA%3D
J Cai M Ikeguchi M Maeta N Kaibara (2000) ArticleTitleMicrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer Surgery 127 32–9 Occurrence Handle10660756 Occurrence Handle1:STN:280:DC%2BD3c7is1GqsQ%3D%3D Occurrence Handle10.1067/msy.2000.100881
N Kurihara T Kubota Y Otani M Ohgami K Kumai H Sugiura et al. (1998) ArticleTitleLymph node metastasis of early gastric cancer with submucosal invasion Br J Surg 85 835–9 Occurrence Handle9667719 Occurrence Handle1:STN:280:DyaK1czjtVaqsQ%3D%3D Occurrence Handle10.1046/j.1365-2168.1998.00743.x
H Matsuzaki S Kikuchi A Kakita (2003) ArticleTitleEvaluation of the morphology of submucosal tumor invasion and its volume in early gastric cancer In Vivo 17 41–4 Occurrence Handle12655788
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sako, A., Kitayama, J., Ishikawa, M. et al. Impact of immunohistochemically identified lymphatic invasion on nodal metastasis in early gastric cancer. Gastric Cancer 9, 295–302 (2006). https://doi.org/10.1007/s10120-006-0396-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10120-006-0396-1