Prevalence of Lynch syndrome among patients with upper urinary tract carcinoma in a Japanese hospital-based population.

Ito T1, Kono K2, Eguchi H3, Okazaki Y3, Yamamoto G4, Tachikawa T4, Akagi K4, Okada Y5, Kawakami S5, Morozumi M5, Tamaru JI6, Ishida H1.

Author information

1: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
2: Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
3: Diagnosis and Therapeutics of Intractable Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan.
4: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
5: Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
6: Department of Pathology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.

Abstract

BACKGROUND:

The prevalence of Lynch syndrome and the use of universal tumor screening to identify Lynch syndrome among unselected patients with upper urinary tract urothelial carcinoma, which is associated with Lynch syndrome, have not been closely investigated yet.

METHODS:

A total of 166 tumors from 164 upper urinary tract urothelial carcinoma patients were tested for microsatellite instability and expression of mismatch repair proteins (MLH1, MHS2, MSH6 and PMS2) by immunohistochemistry. Genetic testing was performed for patients suspected of having Lynch syndrome. Clinicopathological factors, including familial and personal cancer history associated with mismatch repair deficiency, were evaluated.

RESULTS:

The frequency of high-level microsatellite instability and loss of at least one mismatch repair protein was 2.4% (4/164); the microsatellite instability and immunohistochemistry results showed complete concordance. Of these four patients, three were genetically proven to have Lynch syndrome, while the remaining one was highly suggestive for Lynch syndrome based on their personal cancer history. Univariate analysis showed that age<70 years (P = 0.04), ureter as the tumor location (P = 0.052), previous history/synchronous diagnosis of colorectal cancer (P < 0.01) and fulfillment of the criteria per the revised Bethesda guideline (P < 0.01) tended to be or were significantly associated with high-level microsatellite instability/mismatch repair loss.

CONCLUSIONS:

The prevalence of Lynch syndrome among unselected upper urinary tract urothelial carcinoma patients was at least 1.8% in our study population. The screening efficacies of the microsatellite instability test and immunohistochemistry appear equivalent. Universal tumor screening may be a valid approach; however, selective screening methods that consider factors associated with mismatch repair loss/high-level microsatellite instability tumors require further investigation.

KEYWORDS:

Lynch syndrome; immunohistochemistry; microsatellite instability; mismatch repair deficiency; universal tumor screening; upper urinary tract urothelial carcinoma