413 Background: Breast cancer is not a recognised malignant manifestation of Lynch Syndrome which includes colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland, and a genotype phenotype correlation was investigated. One kindred was omitted due to the presence of a biallelic MMR and BRCA1 mutation. The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in 16 pedigrees was as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Six MSH2 mutations and 1 MSH6 mutation were identified in the 7 Lynch syndrome kindreds. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. Final results of immunohistochemistry for mismatch repair protein expression on breast cancer samples are pending and will be reported at the meeting. One breast cancer has been tested to date and demonstrated loss of MSH2 protein expression in an individual carrying an MSH2 mutation. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All reported breast cancer cases were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.
Immune checkpoint B7‐H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer
