RESUMEN
BACKGROUND: Lynch syndrome (LS) due to an inherited damaging mutation in mismatch repair (MMR) genes comprises 3% of all incident colorectal cancer (CRC). Molecular testing using immunohistochemistry (IHC) for MMR proteins is a recommended screening tool to identify LS in incident CRC. This study assessed outcomes of population-based routine molecular screening for diagnosis of LS in a regional center. METHODS: We conducted a prospective, consecutive case series study of universal IHC testing on cases of resected CRC from September 2004-December 2013. Referred cases with abnormal IHC results that attended a familial cancer clinic were assessed according to modified Bethesda criteria (until 2009) or molecular criteria (from 2009). RESULTS: 1612 individuals underwent resection for CRC in the study period and had MMR testing by IHC. Of these, 274 cases (16.9%) exhibited loss of expression of MMR genes. The mean age at CRC diagnosis was 68.1 years (± standard deviation 12.7) and the mean age of those with an IHC abnormality was 71.6 (± 11.8). A total of 82 (29.9%) patients with an abnormal result were seen in a subspecialty familial cancer clinic. Patients aged under 50 (p = 0.009) and those with loss of MSH6 staining (p = 0.027) were more likely to be referred and to attend. After germ-line sequencing, 0.6% (10 of 82) were identified as having a clinically significant abnormality. A further eight probands with pathogenic germ-line mutations were identified from other referrals to the service over the same time period. CONCLUSIONS: While technically accurate, the yield of 'universal' IHC in detecting new Lynch probands is limited by real-world factors that reduce referrals and genetic testing. We propose an alternative approach for universal, incident case detection of Lynch syndrome with 'one-stop' MMR testing and sequencing.
RESUMEN
Cowden's disease (multiple hamartoma syndrome) is a rare genodermatosis, which carries an increased risk of malignancy, especially breast and thyroid carcinoma. Thyroid disease is the most common internal manifestation of the syndrome, but the histological features in benign cases have hitherto been relatively poorly described. Thyroidectomy specimens from four patients with Cowden's disease have been reported in our laboratory in recent years. A number of rather distinctive features were common to all, raising the possibility of a distinctive 'Cowden's thyroid' phenotype.