Colin J R Stewart1,2, David D L Bowtell3,4, Dorota A Doherty2, Yee C Leung2,5. 1. Department of Pathology, King Edward Memorial Hospital, Perth, Western Australia, Australia. 2. School for Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia. 3. Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. 4. Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia. 5. Department of Gynaecological Oncology, King Edward Memorial Hospital, Perth, Western Australia, Australia.
Abstract
AIMS: Gynaecological cancer patients with germline mutations appear to have a better prognosis than those with sporadic malignancies. Following the observation of long-term survival in a patient with stage III ovarian clear cell carcinoma (CCC) and possible Lynch syndrome (LS), DNA mismatch repair (MMR) protein immunohistochemistry was performed in a series of high-stage CCC and correlated with patient outcomes. METHODS AND RESULTS: Thirty-two consecutive cases of stage III/IV ovarian CCCs accessioned between 1992 and 2015 were examined. The tumours from two patients (6%), including the index case, showed loss of MSH2/MSH6 expression while MLH1/PMS2 staining was retained. The index patient subsequently developed colonic and rectal carcinomas that were also MSH2/MSH6-deficient, while the second patient had a genetically confirmed germline MSH2 mutation. All other tumours showed retained expression of the four MMR proteins. The two patients with MMR protein-deficient tumours were alive 160 months and 124 months following surgery, whereas the median survival of patients with MMR protein-intact CCCs was 11.8 months (75th and 25th percentiles of 8.1 months and 39.3 months, respectively), with 21 patients deceased due to tumour. CONCLUSIONS: Larger studies are required but high-stage, MMR protein-deficient CCCs may have a relatively favourable prognosis.
AIMS: Gynaecological cancerpatients with germline mutations appear to have a better prognosis than those with sporadic malignancies. Following the observation of long-term survival in a patient with stage III ovarian clear cell carcinoma (CCC) and possible Lynch syndrome (LS), DNA mismatch repair (MMR) protein immunohistochemistry was performed in a series of high-stage CCC and correlated with patient outcomes. METHODS AND RESULTS: Thirty-two consecutive cases of stage III/IV ovarian CCCs accessioned between 1992 and 2015 were examined. The tumours from two patients (6%), including the index case, showed loss of MSH2/MSH6 expression while MLH1/PMS2 staining was retained. The index patient subsequently developed colonic and rectal carcinomas that were also MSH2/MSH6-deficient, while the second patient had a genetically confirmed germline MSH2 mutation. All other tumours showed retained expression of the four MMR proteins. The two patients with MMR protein-deficient tumours were alive 160 months and 124 months following surgery, whereas the median survival of patients with MMR protein-intact CCCs was 11.8 months (75th and 25th percentiles of 8.1 months and 39.3 months, respectively), with 21 patients deceased due to tumour. CONCLUSIONS: Larger studies are required but high-stage, MMR protein-deficient CCCs may have a relatively favourable prognosis.
Authors: Julia A Beaver; Robert L Coleman; Rebecca C Arend; Deborah K Armstrong; Sanjeeve Bala; Gordon B Mills; Anil K Sood; Thomas J Herzog Journal: Clin Cancer Res Date: 2019-05-24 Impact factor: 12.531
Authors: Flurina A M Saner; Alan Herschtal; Brad H Nelson; Anna deFazio; Ellen L Goode; Susan J Ramus; Ahwan Pandey; Jessica A Beach; Sian Fereday; Andrew Berchuck; Stephanie Lheureux; Celeste Leigh Pearce; Paul D Pharoah; Malcolm C Pike; Dale W Garsed; David D L Bowtell Journal: Nat Rev Cancer Date: 2019-06 Impact factor: 60.716