Lynch syndrome screening in gynaecological cancers: results of an international survey with recommendations for uniform reporting terminology for mismatch repair immunohistochemistry results.

AIMS: Lynch syndrome (LS) is associated with an increased risk of developing endometrial carcinoma (EC) and ovarian carcinoma (OC). There is considerable variability in current practices and opinions related to screening of newly diagnosed patients with EC/OC for LS. An online survey was undertaken to explore the extent of these differences. METHODS AND RESULTS: An online questionnaire was developed by a panel of experts and sent to all members of the British Association of Gynaecological Pathologists (BAGP) and the International Society of Gynecological Pathologists (ISGyP). Anonymised results were received and analysed. Thirty-six BAGP and 44 ISGyP members completed the survey. More than 90% of respondents were aware of the association of LS with both EC and OC, but 34% were not aware of specific guidelines for LS screening. Seventy-one per cent of respondents agreed that universal screening for LS should be carried out in all newly diagnosed EC cases, with immunohistochemistry (IHC) alone as the preferred approach. Only 36% of respondents currently performed IHC or microsatellite instability testing on all newly diagnosed EC cases, with most of the remaining respondents practising selective screening, based on clinical or pathological features or both. A significant minority of respondents (35%) believed that patient consent was required before performance of mismatch repair (MMR) protein IHC. Almost all respondents favoured the use of standardised terminology for reporting MMR protein staining results, and this is proposed herein. CONCLUSION: There is wide support for universal LS screening in patients with EC, but this survey highlights areas of considerable variation in practice.

Synovial sarcoma of the vulva: a case report.

INTRODUCTION: Contrary to its name, synovial sarcoma does not arise from the synovial membrane but from multipotent stem cells and can present in any part of the body. Very few cases of vulval synovial sarcoma have been reported in the literature; we report on such a presentation. These tumors can present as painless lumps, which must be completely excised to give the best prognosis. Therefore the diagnosis of synovial sarcoma should always be kept in mind in the management of vulval masses, especially in young patients. CASE PRESENTATION: We report the case of a 28-year-old Caucasian woman with synovial sarcoma of the vulva. Complete excision was possible in this case. CONCLUSION: We have presented a rare case of synovial sarcoma of the vulva, which can be easily confused with lipoma of the vulva. The management of this tumor requires referral to a cancer centre, with a multidisciplinary approach.

Serum biomarkers which correlate with failure to respond to immunotherapy and tumor progression in a murine colorectal cancer model.

PURPOSE: To advance our understanding of mechanisms involved in tumor progression/regression, a CT26 colorectal mouse model treated intra-tumorally with DISC-herpes simplex virus as immunotherapy was used in the discovery and validation phases to investigate and ultimately identify biomarkers correlating with the failure to respond to immunotherapy. EXPERIMENTAL DESIGN: For the discovery phase, serum protein/peptide profiles of a retrospective sample collection (total n=70) were analyzed using MALDI-TOF-MS combined with artificial neural networks. Following identification of the key predictive peptides using ESI-MS/MS, validation of the identified proteins was carried out on serum and tissues collected in an independent sample set (total n=60). RESULTS: Artificial neural network analysis resulted in four discriminatory peaks with an accuracy of 86%, sensitivity of 90% and specificity of 81% between the progressor/regressor groups. Three of the identified discriminatory markers were upregulated and demonstrated a positive correlation with tumor progression following DISC-herpes simplex virus therapy. Immunovalidation studies corroborated the MALDI-TOF-MS findings. Immunohistochemistry revealed that serum amyloid A-1 and serum amyloid P produced in the liver localized intracellularly in CT26 tumor tissue. CONCLUSIONS: MALDI-TOF-MS and BI analysis of the serum proteome of tumor-bearer mice undergoing immunotherapy, identified biomarkers associating with "failure to respond" and biological arrays confirmed these findings.