Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma.
BACKGROUND
Endoscopic treatment has been increasingly used for T1 esophageal squamous cell carcinoma (ESCC). However, this therapy is sometimes incomplete if the depth of the T1 primary tumor reaches the muscularis mucosae or submucosal layer because these tumors have a relatively high incidence of lymph node metastasis. However, to our knowledge, no previous reports on the prediction of nodal metastasis determined by evaluating primary tumor specimens of patients with ESCC are available.


METHODS
A total of 55 patients with T1 ESCC invading as deep as the submucosal layer who underwent curative esophagectomy were examined. We investigated the significance of the immunohistochemical staining of Vascular endothelial growth factor-C (VEGF-C) and E-cadherin in the primary tumor and Tumor budding for prediction of nodal metastasis.


RESULTS
Metastasis to the regional lymph nodes was observed in 26 cases (47.3%) in this setting. VEGF-C expression and reduced E-Cadherin expression in the primary tumor was observed in 32 (58.1%) and 38 cases (69.1%), respectively. High-grade tumor budding was observed in 29 cases (52.7%). E-cadherin expression and tumor budding were closely correlated with nodal metastasis (p=0.04 and <0.01 respectively), whereas VEGF-C expression tended to correlate with lymph node metastasis (p=0.06). In addition, high-grade tumor budding was significantly correlated (p<0.01) with reduced E-cadherin expression. The accuracy of tumor budding and E-cadherin expression for nodal metastasis were 67.3% and 65.4% respectively, comparable with the one of lymphatic involvement (63%). Tumor budding (p<0.01), but not E-cadherin and VEGF-C expression, was significantly correlated with poor survival.


CONCLUSIONS
After the endoscopic treatment, additional therapy, such as surgery or chemoradiotherapy, may be required if reduced E-cadherin expression and high-grade tumor budding are observed in primary tumor specimen.
Department of Surgical Oncology, Graduate School of Medicine, Osaka City University 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. k-naoshi@med.osaka-cu.ac.jp.
Yasuo
Y
Nakagawa
Masaichi
M
Ohira
Naoshi
N
Kubo
Yoshito
Y
Yamashita
Katsunobu
K
Sakurai
Takahiro
T
Toyokawa
Hiroaki
H
Tanaka
Kazuya
K
Muguruma
Masatsune
M
Shibutani
Sadaaki
S
Yamazoe
Kenjiro
K
Kimura
Hisashi
H
Nagahara
Ryosuke
R
Amano
Hiroshi
H
Ohtani
Masakazu
M
Yashiro
Kiyoshi
K
Maeda
Kosei
K
Hirakawa
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016629:Esophagectomy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C
E-cadherin; T1 Esophageal cancer; nodal metastasis; tumor budding