Cancer-Associated Lymphatic and Venous Vessels in Colonic Carcinomas

Abstract

Objective: Colonic carcinomas spread to regional lymph nodes and liver. There are cancer-associated lymphatic and venous vessels at the margin of colonic carcinomas, which facilitate spreading carcinoma through lymphatic and venous vessels. This study aimed to examine cancer-associated lymphatic and venous vessels in TNM T1 to T3 carcinomas using lymphatic vessel hyaluronan receptor for lymphatic vessels and von Willebrand factor for venous vessels by immunocytochemical staining. Materials and Methods: A total of 40 cases of moderately differentiated colonic carcinoma were studied using routinely formalin-fixed and paraffin-embedded sections. The cases consisted of 10 cases of TNM T1, 15 cases each of T2 and T3 cases. Immunocytochemical staining was performed using goat antihuman LYVE-1for lymphatic vessels and rabbit antihuman von Willebrand factor for venous vessels. Results: In TNM T1 carcinoma, increased, irregular and narrow lymphatic and venous vessels were present in the adjacent normal mucosa to the carcinoma, some of which penetrated cancerous lesion. There were no tumor emboli in lymphatic and venous vessels. In TNM T2 carcinoma, there were few lymphatic and venous vessels in midst of the carcinoma whereas numerous small lymphatic and venous vessels were present within muscle layers adjacent to the invading carcinoma. Extramural tumor embolus was present in submucosa in one case. In TNM T3 carcinoma, cancer has invaded through the muscle layers where dilated lymphatic and venous vessels were present adjacent to cancerous nests. Tumor emboli were identified in two cases by immunocytochemical staining. Conclusion: The current study showed cancer-associated lymphatic and venous vessels at the interface in TNM T1 carcinoma to dilated intramuscular lymphatic and venous vessels adjacent to invading cancerous nests in TNM T3 carcinoma, and supports cancerous cells spread via lymphatic and venous vessels through muscle layers to subserosa as supported by tumor emboli in the lymphovascular system. T. Tomita 102

Immunohistochemical Staining for Lymphatic and Blood Vessels in Normal Tissues: Comparison between Routinely Paraffin-Embedded Tissues and Frozen Sections

“…The colonic sections showed a few lymphatic vessels in lamina propria but showed numerous lymphatic vessels in the submucosa (Figure 3-A). Kennedy et al reported absent lymphatic vessels in lamina propria of the normal human colon with some lymphatic vessels in most cases with inflammation and neoplasia (12). We believe their negative staining was due to non-optimal preservation of lymphatic vessels in paraffin-embedded colonic tissue.…”

“…We believe their negative staining was due to non-optimal preservation of lymphatic vessels in paraffin-embedded colonic tissue. Colon lacks lacteals seen in the small intestine but is well supplied with lymphatic vessels in lamina propria, and the highest densities of lymphatic vessels are found in the submucosa (12). Both lymphatic and blood vessels penetrated longitudinally through the colonic muscle wall to the subserosa (Figure 3-C and -D) (11), through which colonic cancer cells may spread to the pericolonic lymph nodes (38,39).…”

“…We found that frozen sections were superior for lymphatic and blood vessels immunostaining than the routinely formalin-fixed and paraffin-embedded sections (11,12). To anatomic pathologists, it is crucially important to identify the precise presence of lymphatic and blood vessels in the normal organs and the pathological tissue specimens, especially in cancer tissues (11,12). The classical staining for lymphatic vessels is van Gieson's stain for the lining elastic lamina for distinguishing lymphatic vessels from the small tissue spaces due to the fixation artifacts by buffered formalin-fixation and paraffin embedding.…”

“…These tissues included colon and pancreas. Immunocytochemical staining procedures with paraffin-embedded tissues were previously reported (11,12). The sources of antibodies used for immunocytochemical staining and each dilution of the antibody for routinely formalin-fixed and paraffin-embedded tissues and frozen sections are as follows (Table 1).…”

“…We had previously performed such immunocytochemical staining with normal tissues. We found that frozen sections were superior for lymphatic and blood vessels immunostaining than the routinely formalin-fixed and paraffin-embedded sections (11,12). To anatomic pathologists, it is crucially important to identify the precise presence of lymphatic and blood vessels in the normal organs and the pathological tissue specimens, especially in cancer tissues (11,12).…”