Lymphatic invasion according to D2‐40 immunostaining is a strong predictor of nodal metastasis in superficial squamous cell carcinoma of the esophagus: Algorithm for risk of nodal metastasis based on lymphatic invasion

Abstract

In squamous cell carcinoma (SCC) of the esophagus, D2-40 immunostaining has recently been used to detect lymphatic invasion, but invasion detected using D2-40 immunostaining for a predictor of nodal metastasis was controversial. Therefore, the usefulness of detecting lymphatic invasion by D2-40 immunostaining as a predictor of nodal metastasis was examined in superficial (mucosal and submucosal) SCC of the esophagus. A total of 115 superficial SCC of the esophagus were examined on immunohistochemistry using D2-40. It was found that lymphatic invasion demonstrated on D2-40 immunostaining was mainly detected in the lamina propria mucosa. Lymphatic invasion was found in 37 cases and the invasion detected in the entire tumor tissue was statistically correlated with nodal metastasis. Based on the lymphatic invasion according to D2-40 immunostaining, an algorithm was devised for the risk (low, intermediate and high) of nodal metastases in superficial SCC in the esophagus. In conclusion, the detection of lymphatic invasion on D2-40 immunostaining in tumor tissue is a strong predictor for nodal metastasis in superficial SCC of the esophagus. Lymphatic invasion was found mainly in the lamia propria mucosa, thus the devised algorithm is useful for determining the optimal treatment strategy after endoscopic mucosal resection for esophageal SCC.

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

“…This is in accordance with studies investigating a risk factor predictive of nodal involvement in colorectal, vulvar and esophageal cancer [11,21,26]. Our observations indicate that the main source of lymph node metastasis may be delivered from the lymphatic invasion in esophageal cancer.…”

“…Tomita et al [26] obtained similar results. Lymph node metastasis was significantly (p < 0.001) related with the tissue status of lymphatic invasion, which were diagnosed by D2-40 immunohistochemistry.…”

Prediction model of lymph node metastasis in superficial esophageal adenocarcinoma and squamous cell cancer including D2‐40 immunostaining

“…D2-40, a specific marker for lymphatic epithelium has been shown to detect lymphatic infiltration occurring in association with subepithelial extension in superficial squamous cell carcinoma of the esophagus [15]. Moreover, lymphatic infiltration according to D2-40 immunostaining was a strong predictor of nodal metastasis in superficial squamous cell carcinoma of the esophagus [16].…”

THORACIC SURGERY Intratumoral lymphatic vessel density, and intratumoral and peritumoral lymphatic vessel invasion as predictive factors of lymph node metastasis and prognostic factors in esophageal cancer

“…Lin et al [22] have reported similar observations for colorectal cancer. Imamura et al [17], Tomita et al [18] and our earlier study [23] revealed that LVI in the entire tumor tissue of esophageal cancer was significantly linked with nodal metastasis. In contrast, Mori et al [15] found that only ptLVI positively correlated with lymph node metastasis.…”

“…In contrast, Mori et al [15] did not find any correlation between LVD and pathological parameters. High itLVD was found to be significantly correlated with lymph node metastasis by Inoue et al [16] and Imamura et al [17] in esophageal cancer, and by Tomita et al [18] only in subepithelial extension of esophageal cancer. A recent study suggested that intratumoral lymphatics play a greater role than peritumoral lymphatics in nodal metastasis of head and neck cancer [19].…”