syndrome screening in endometrial cancer can be improved.• Gynaecologists ought to be aware of Lynch syndrome screening in endometrial cancer and might require additional training.• Quality assurance protocols should be implemented to ensure adherence to Lynch syndrome screening in endometrial cancer.
Immunohistochemistry (IHC) for DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 is used for microsatellite instability (MSI) screening in colorectal carcinoma (CRC) and endometrial carcinoma (EC). Loss of PMS2, with retained MLH1 staining occurs in germline mutations of PMS2 gene, and is an indication for genetic testing. We report a pitfall of immunohistochemical interpretation in an EC, initially regarded as MLH1-positive and PMS2-negative. Review of the MLH1-IHC (M1-clone) revealed a granular, dot-like, nuclear staining. On repeating the MLH1-IHC with a different clone (ES05-clone), complete negativity was noted, and on molecular testing, MLH1 promotor methylation was detected. The dot-like pattern was therefore adjudged a clone-dependent artefact. On reviewing the archived MLH1-IHC slides, we observed the same dot-like pattern in two CRCs; in both cases the M1-clone had been used. Awareness of this artefact may prevent reporting errors, and unnecessary referrals for germline mutation testing.
even after multiple chemotherapy lines, platinum sensitivity is associate with a longer therapy-free interval. The aim of this study was to investigate platinum resistance in long-term OvCa survivors. Methodology Patients diagnosed with OvCa at the Tuebingen University Women's Hospital between 2000 and 2012 were retrospectively identified and follow-up data was collected. For patients surviving at least 8 years a detailed chart review was performed. Platinum resistance was defined as disease progression during platinum-based chemotherapy or 6 months after the last platinum dose administration. Result(s)* From a total n=745 of patients with adequate follow-up data, n=223(30%) survived at least 8 years after primary diagnosis. Median follow-up was 12.1 years and median age at diagnosis was 54.7 years. Relapse was recorded in 87/ 223(39%) patients, of which 28/87(32%) developed platinum resistance at some point. Platinum resistance was observed after the second line chemotherapy in most patients (median: 2, range: 1-4). 23/28 patients received further chemotherapy lines (median: 2, range: 0-8). Rechallenge with a platinumbased chemotherapy has been used in 9/28(32%) patients. Median overall survival of these 28 patients was 9.3 years (8.2-18.4, IQR3.7) and 4.1 (0.4-16.8, IQR3.8) years after platinum resistance. Conclusion* We were able to demonstrate long-term survival after platinum resistance in a substantial number of ovarian carcinoma patients. Suggesting therefore, that other parameters influence the disease behaviour. Further research of patient characteristics, environmental and genetic features and treatment modalities will help to further understand factors contributing to long-term survival.
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