The Conspicuousness of High Endothelial Venules in Angioimmunoblastic T-cell Lymphoma Is Due to Increased Cross-sectional Area, Not Increased Distribution Density

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a T-cell lymphoma of follicular helper T-cell origin. Histologically, neoplastic T-cells proliferate to form clusters adjacent to or between arborizing high endothelial venules (HEVs). HEVs in normal lymph nodes express sulfated glycans called peripheral lymph node addressin (PNAd); however, it remains unclear whether PNAd is also expressed on HEVs in AITL. Furthermore, although it is widely accepted that HEVs are conspicuous in AITL due to their proliferation, quantitative histological support for this concept is lacking. To investigate these issues, we employed monoclonal antibodies recognizing PNAd, namely, MECA-79, HECA-452, and 297-11A, and performed quantitative immunohistochemical analysis of HEVs in 36 AITL-affected and 67 normal lymph nodes. Staining with all three antibodies confirmed that AITL HEVs express PNAd. Moreover, AITL HEVs were bound calcium-dependently by L-selectin-IgM fusion proteins, indicating that they function in the recruitment of L-selectin-expressing lymphocytes. Unexpectedly, HEV distribution density was not increased but rather decreased in AITL compared with normal lymph nodes, but HEV cross-sectional area in AITL was significantly greater than that seen in normal lymph nodes. Overall, these results indicate that the prominence of AITL HEVs is likely due to increased cross-sectional area rather than increased distribution density.

Vascular E-selectin Expression Detected in Formalin-fixed, Paraffin-embedded Sections With an E-selectin Monoclonal Antibody Correlates With Ulcerative Colitis Activity

“…6 Taking advantage of this sLe x /sLe a -specific carbohydratebinding property of E-selectin, we previously used an E-selectin•IgM chimera, which is a soluble form of E-selectin, to functionally probe sLe x and/or sLe a in formalin-fixed, paraffin-embedded (FFPE) tissue sections of various human diseases, including chronic Helicobacter pylori gastritis, 7 ulcerative colitis, 8 testicular seminoma, 9 bladder urothelial carcinoma, 10 papillary thyroid carcinoma, 11 clear cell renal cell carcinoma, 12 and most recently, angioimmunoblastic T-cell lymphoma. 13 Immunohistological analysis of the E-selectin molecule itself, however, has been hampered by lack of E-selectin-specific monoclonal antibodies capable of staining FFPE tissue sections; thus researchers had no choice but to use frozen tissue sections. In the case of ulcerative colitis, immunohistological analysis of E-selectin has been conducted with a limited number of frozen tissue sections using monoclonal antibodies such as BB11 (mouse IgG 2b ), 14,15 BBIG-E6 (mouse IgG 1 ; R&D Systems, Minneapolis, MN), 16 and 1.2B6 (mouse IgG 1 ; Bio-Rad, Hercules, CA).…”

“…6 Taking advantage of this sLe x /sLe a -specific carbohydrate-binding property of E-selectin, we previously used an E-selectin•IgM chimera, which is a soluble form of E-selectin, to functionally probe sLe x and/or sLe a in formalin-fixed, paraffin-embedded (FFPE) tissue sections of various human diseases, including chronic Helicobacter pylori gastritis, 7 ulcerative colitis, 8 testicular seminoma, 9 bladder urothelial carcinoma, 10 papillary thyroid carcinoma, 11 clear cell renal cell carcinoma, 12 and most recently, angioimmunoblastic T-cell lymphoma. 13…”