CTSD and urinary bladder cancer: Based on initial analysis of ki-67 pattern distributions in bladder cancer, as well as reports employing protease cathepsin-D and pro-cathepsin-L staining within a cohort of vulvar carcinomas, early studies defined two patterns of ki-67 staining on vulva carcinomas: a “localized” distribution of ki-67-positive nuclei restricted to basilar components of tumor clusters and a “diffuse” pattern, with ki-67-positive nuclei spreading universally all over the tumor mass [49,62,63].