Immunohistochemical verification of clinically assumed lynch syndrome among patients with colorectal and uterine cancer

C. Strub-Antonucci, M. Nowak, J. Diebold, J. Metzger, M. Sykora

Objective

Lynch syndrome (LS) is the most common type of hereditary colorectal disease. It counts for 2-4% of all Colorectal Carcinomas (CRC). Further, the incidence of LS in patients with uterine cancer is still undervalued. Until the start of our pilot study the Amsterdam-II and Bethesda criteria, which are used for the clinical diagnosis of LS, were used sporadically in our institution and no immunohistochemical examination was performed. We wanted to verify these two clinical tests by Immunohistochemy (IHC) to improve the detection rate of patients with LS in Central Switzerland, as it has been shown that 10 to 25% of the population remains undiagnosed.

Methods

The ethical committee of Lucerne approved this study. All patients who were planned for an operation because of a diagnosed or suspected CRC or uterine carcinoma and signed the patient consent form were included in this study. Revised Bethesda and Amsterdam-II criteria were assessed and postoperatively an IHC was conducted. Patients with high risk for Lynch Syndrome were sent to a geneticist to be assessed further.

Results

We examined 34 patients, 2 of them with uterine cancer, the other patients with a colorectal carcinoma. There were 2 patients lacking the expression of MLH1, PMS2, MSH2 or/and MSH6 (mutated MMR genes leading to a microsatellite instability responsible for LS) in the immunohistology. Both had negative Amsterdam-II and revised Bethesda criteria. No patient fulfilled the Amsterdam-II-criteria and 5 patients fulfilled the Bethesda criteria, but none of them showed a positive immunohistochemistry.

Conclusion

With this study we show that Lynch Syndrome should not only be considered in patients with CRC, but also in those with uterine cancer, as one of our two gynecological patients had a positive IHC. We also found both patients with a positive IHC neither fulfilling the revised Bethesda nor the Amsterdam-II-criteria. This is why we decided to continue to ask for an IHC on all our patients with a CRC and uterine cancer. We also found the revised Bethesda-criteria to be little specific as 5 patients fulfilled it, but didn’t have a positive IHC. We propose that Amsterdam-II and revised Bethesda criteria may be of use for finding families with a high risk for hereditary CRC, but are not useful for families with Lynch Syndrome. Having a small sample size in this study we propose further examination of our results.

Table: Summary of the results
Figure: Example of the genealogical tree of a patient with fulfilled Bethesda criteria