Upper tract urothelial carcinoma: a clinicopathologic study including microsatellite instability analysis

Area of Science:

• Uro-oncology
• Cancer genetics
• Molecular pathology

Background:

• Hereditary nonpolyposis colorectal cancer syndrome (Lynch syndrome) is linked to DNA mismatch repair gene mutations and microsatellite instability.
• Urothelial carcinoma of the renal pelvis and ureter can be a manifestation of this hereditary cancer syndrome.

Purpose of the Study:

• To investigate microsatellite instability (MSI) in upper tract urothelial carcinoma (UTUC).
• To correlate MSI with clinicopathologic features and patient history of other cancers.

Main Methods:

• Analysis of microsatellite instability in 114 UTUC patients' tumor and normal DNA.
• Correlation of MSI status with clinical data, including additional nonurologic cancers and family cancer history.
• Evaluation of grade, stage, and MSI as predictors of cancer-specific survival.

Main Results:

• Microsatellite instability was detected in 31.3% of evaluable UTUC tumors, the highest frequency reported to date.
• Patients with MSI-unstable UTUC were more likely to have additional nonurologic cancers (especially colorectal) and a family history of colorectal cancer.
• Higher grade UTUC was also associated with MSI, but MSI status did not predict cancer-specific survival; grade and stage were stronger predictors.

Conclusions:

• UTUC exhibits a high frequency of MSI, suggesting it can serve as a marker for hereditary nonpolyposis colorectal cancer syndrome.
• Identifying MSI in UTUC patients is crucial for detecting Lynch syndrome and initiating surveillance in affected individuals and their relatives.