Phenotype-dependent heterogeneity of THSD7A expression in gastric cancer tissue in a patient with THSD7A-associated membranous nephropathy.

An 88-year-old Japanese man with benign prostatic hyperplasia was presented to our hospital because of proteinuria and generalized edema. He was diagnosed with nephrotic syndrome and underwent a kidney biopsy, which revealed thickening of the capillary wall, spike formation, and subepithelial deposits, leading to histopathological diagnosis of membranous nephropathy. IgG4-dominant deposits were observed in IgG subclass staining, and immunostaining for thrombospondin type 1 domain-containing 7A (THSD7A) demonstrated granular staining along the capillary wall. A malignancy screening was performed, which led to the detection of gastric cancer. Malignancy-associated membranous nephropathy secondary to gastric cancer was suspected, and priority was given to the treatment of gastric cancer. Three months after undergoing radical surgery for gastric cancer, his nephrotic syndrome achieved remission. The histopathological diagnosis of gastric cancer was papillary adenocarcinoma. In the surgical specimen of the gastric cancer, THSD7A was positive in the tumor cells with intestinal phenotype and negative in gastric foveolar phenotype. These findings suggest that the acquisition of the ability to express THSD7A by cancer transformation in multi-step carcinogenesis of gastric cancer may be involved in the development of malignancy-associated membranous nephropathy.