Strong expression of chemokine receptor CCR9 in diffuse large B-cell lymphoma and follicular lymphoma strongly correlates with gastrointestinal involvement.

The gastrointestinal (GI) tract is the most common site of extranodal B-cell lymphomas. However, it is unclear how neoplastic lymphoid cells preferentially home there. We hypothesize that expression of the GI-homing chemokine receptor CCR9 may account for the dissemination of B-cell lymphomas to the GI tract. To test our hypothesis, we compared the expression of CCR9 using immunohistochemistry on GI versus nodal diffuse large B-cell lymphoma and follicular lymphoma. We found that 27 (66%) of 41, 12 (29%) of 41, and 2 (5%) of 41 of GI lymphoma cases demonstrated 3+, 2+, and 1+ CCR9 staining, respectively. In contrast, 2 (5%) of 39, 5 (13%) of 39, 8 (20.5%) of 39, and 24 (61.5%) of 39 nodal-restricted lymphoma cases demonstrated 3+, 2+, 1+, and 0+ CCR9 staining (P < .0001). This was observed for both diffuse large B-cell lymphoma (P < .001) and follicular lymphoma (P < .001). We also compared the expression of CCR9 on nodal B-cell lymphomas with involvement of the GI tract with those restricted to the lymph node. We found that 10 (62%) of 16, 3 (19%) of 16, and 3 (19%) of 16 nodal lymphomas with GI involvement showed 3+, 2+, and 1+ CCR9 staining, respectively. In contrast, 2 (5%) of 39, 5 (13%) of 39, 8 (20.5%) of 39, and 24 (61.5%) of 39 nodal lymphomas without GI involvement demonstrated 3+, 2+, 1+, and 0+ CCR9 staining, respectively (P < .001). Our finding that CCR9 expression is elevated in the nodal lymphomas of patients with GI involvement suggests the potential clinical utility of chemokine receptor status, as assessed by immunohistochemistry, to potentially predict GI dissemination and progression to higher stage in patients who initially present with limited nodal-restricted disease.