Independent histological risk factors for lymph node metastasis of superficial esophageal squamous cell carcinoma; implication of claudin-5 immunohistochemistry for expanding the indications of endoscopic resection

Abstract

Endoscopic resection is curative for superficial esophageal squamous cell carcinoma (ESCC) limited to the lamina propria. Endoscopic resection is not recommended for superficial ESCC invading muscularis mucosa or submucosa, however, because of the high frequency of lymph node metastasis (LNM) in such patients. Methods to more accurately predict LNM by analysis of endoscopically resected specimens are needed. Patients with superficial ESCC who underwent surgery without prior chemoradiotherapy (n= 110) were retrospectively examined to determine whether LNM correlated with immunohistochemical parameters and conventional histological parameters, including depth of invasion and vascular permeation. Cancer cell expression of claudins-1, 5, and 7, E-cadherin, beta-catenin, and matrix metalloproteinase 7 was evaluated. Univariate analysis revealed that LNM correlated with claudin-5 expression, but not any other immunohistochemical parameter examined. Multivariate analysis revealed three independent risk factors for LNM: aberrant claudin-5 expression in cancer cells (odds ratio; OR [95% confidence interval]= 4.61[1.44-14.77]), depth of submucosal invasion greater than 200 microm (3.55 [1.02-13.17]), and positive lymphatic permeation (3.34 [1.22-9.15]). LNM was found in one of 29 (3.4%) patients with none of these three risk factors, and in 32 of 81 (39.5%) patients with one or more of these risk factors. In superficial ESCC, routine analysis of claudin-5 expression in cancer cells together with depth of invasion and lymphatic permeation may be useful for predicting LNM and thereby reducing the number of patients undergoing additional surgery after successful endoscopic resection.

Advantages of endoscopic submucosal dissection versus endoscopic oblique aspiration mucosectomy for superficial esophageal tumors

“…The tissue specimens were embedded in paraffin, sectioned at 4 µm, stained with hematoxylin–eosin, and additionally stained with elastica van Gieson to assess the depth of tumor invasion and venous invasion. The depth of tumor invasion was classified as follows: EP, an epithelial tumor; LPM, a mucosal tumor with invasion to the lamina propria; MM, a mucosal tumor that almost invades the muscularis mucosae; SM1, a tumor that extends up to 200 µm below the lower border of the muscularis mucosae; and SM2, a tumor that extends more than 200 µm below the lower border of the muscularis mucosae 14 . En bloc resected lesions with tumor‐negative margins histologically were considered as completely resected.…”

Ten year experience of esophageal endoscopic submucosal dissection of superficial esophageal neoplasms in a single center.

“…Submucosal invasion (SMI) was defined as a tumor extending beyond the muscularis mucosa, including Sm1. Sm1 was defined as a submucosally invaded tumor that extended up to 200 μm below the lower border of the muscularis mucosa [29].…”

The role of claudin-5 in blood-brain barrier (BBB) and brain metastases (Review)

“…One of the characteristics of a metastatic tumour is significant peritumoural edema, which may be explained as a result of the alteration in TJs and claudin-5. In superficial oesophageal squamous cell carcinoma, lymph node metastasis was observed to be associated with claudin-5 expression, although the exact mechanism is undetermined (93).…”