Endometrial carcinoma expresses an increased cathepsin B/D ratio.

Objectives: Cathepsins B and D belong to a family of proteases involved in tumor invasion and metastasis. As such they may function as biomarkers for the aggressiveness of a given tumor. We examined the enzymatic activity of these proteins as well as the cellular and extracellular distribution of cathepsins B and D.

Methods: 39 snap frozen tissue samples were assayed for activity fluorometrically with cathepsin-specific peptide substrates in combination with specific inhibitors. 4 groups were established: benign tissue, stage I/grade 1, stage i/grade 3, and stage IIIC/any grade. IHC staining for cathepsin B with the percentage of counterstained enzyme calculated from each specimen.

Results: A significantly increased level of cathepsin B activity was seen in malignant tissue specimens when compared to benign tissue. The cathepsin B/D ratio confirmed and was required to detect the significance of this distinction for each malignant group when compared to benign samples. There were no differences in cathepsin B or D expression detected between the various malignant groups. IHC staining for cathepsin B was more diffuse in the malignant tissues.

Conclusions: Malignant endometrium displays increased cathepsin B activity when compared benign samples. The cathepsin B/D ratio is increased for each of the malignant groups studied when compared directly to benign endometrium. The cathepsin B/D ratio cannot be utilized to distinguish the stage or grade between any of the malignant groups studied. This ratio may serve to distinguish malignant from benign tumor samples and may be a constitutive change in the malignant transformation.