TOPIC DISCUSSION: Is THSD7A the paraneoplastic marker for Membranous GN associated with cancer?

Two recent papers from Germany have now associated the thrombospondin type 1 domain containing 7A(THSD7A) as a target antigen identified in membranous GN  in association with cancer.   In a large study, the authors screened > 1200 patients for western blot analysis for THSD7A. The incidence was 2.6%. They were mostly women.  In this cohort, the percentage of patients with THSD7A-associated MN and malignant disease significantly exceeded that of patients with PLA₂R-associated MN and malignant disease. In all cohorts, they identified 40 patients with THSD7A-associated MN, eight of whom developed a malignancy within a median time of 3 months from diagnosis of MN. In one patient with THSD7A-associated MN and metastases of an endometrial carcinoma, immunohistochemistry showed THSD7A expression on the metastatic cells and within follicular dendritic cells of the metastasis–infiltrated lymph node. 

In a separate report in NEJM, the same group described a case of gall bladder cancer and membranous GN. The patient had circulating THSD7A antibodies and THSD7A antigen positive membranous GN.  The primary gall bladder tumor and lymph nodes also stained for THSD7A on the immunohistochemical analysis.  Following chemotherapy, the THSD7A antibodies in plasma were no longer detectable and proteinuria improved as well. In that study, when additional 1009 patients with membranous were reviewed, 25 had positive THSD7A antibodies. Of the 25, 7 had malignant tumors.

Patients with THSD7A-associated MN differ in their clinical characteristics from patients with PLA₂R1-associated MN, and more intensive screening for the presence of malignancies may be warranted in those with THSD7A-associated MN.