Laura Casey1, Martin Köbel2, Raji Ganesan3, Simone Tam1, Rajeev Prasad4, Steffen Böhm5, Michelle Lockley5, Arjun J Jeyarajah6, Eleanor Brockbank6, Asma Faruqi1, C Blake Gilks7, Naveena Singh1. 1. Department of Cellular Pathology, Barts Health NHS Trust, London, UK. 2. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada. 3. Department of Cellular Pathology, Birmingham Women's Hospital, Birmingham, UK. 4. Department of Cellular Pathology, Queen's Hospital, Romford, UK. 5. Barts Cancer Institute, Queen Mary University of London, London, UK. 6. Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK. 7. Department of Anatomic Pathology, Vancouver General Hospital, Vancouver, BC, Canada.
Abstract
AIMS: The treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples, and the first surgical sample is often taken post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neoadjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre-chemotherapy and post-chemotherapy samples of HGSC. METHODS AND RESULTS: Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre-chemotherapy and post-chemotherapy. p53 IHC was recorded as normal (wild-type) or abnormal (mutation-type), and was further classified as overexpression, complete absence, or cytoplasmic. WT1 IHC was classified as positive or negative. A subset of cases were further assessed for the extent of nuclear immunoreactivity of WT1 by use of the H-score. Fifty-seven paired samples were stained with p53. Fifty-six of 57 (98%) cases showed mutation-type p53 staining. Pre-chemotherapy and post-chemotherapy IHC results were concordant in 55 of 57 (96%) cases. For WT1, pre-chemotherapy and post-chemotherapy IHC results were concordant in 56 of 58 (97%) cases. In 23 paired WT1 cases, the mean post-treatment H-score decreased from 227 [range 20-298, standard deviation (SD) 64] to 151 (range 0-288, SD 78) (P = 0.0008). CONCLUSIONS: Immunohistochemical expression of p53 (abnormal/mutation-type pattern) and WT1 in HGSC is almost universal and is largely concordant before and after chemotherapy. This finding underscores the reliability of these diagnostic markers in small samples and in surgical samples following neoadjuvant chemotherapy, with very few exceptions. A novel finding was the significant diminution in intensity of WT1 staining following chemotherapy.
AIMS: The treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples, and the first surgical sample is often taken post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neoadjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre-chemotherapy and post-chemotherapy samples of HGSC. METHODS AND RESULTS: Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre-chemotherapy and post-chemotherapy. p53 IHC was recorded as normal (wild-type) or abnormal (mutation-type), and was further classified as overexpression, complete absence, or cytoplasmic. WT1 IHC was classified as positive or negative. A subset of cases were further assessed for the extent of nuclear immunoreactivity of WT1 by use of the H-score. Fifty-seven paired samples were stained with p53. Fifty-six of 57 (98%) cases showed mutation-type p53 staining. Pre-chemotherapy and post-chemotherapy IHC results were concordant in 55 of 57 (96%) cases. For WT1, pre-chemotherapy and post-chemotherapy IHC results were concordant in 56 of 58 (97%) cases. In 23 paired WT1 cases, the mean post-treatment H-score decreased from 227 [range 20-298, standard deviation (SD) 64] to 151 (range 0-288, SD 78) (P = 0.0008). CONCLUSIONS: Immunohistochemical expression of p53 (abnormal/mutation-type pattern) and WT1 in HGSC is almost universal and is largely concordant before and after chemotherapy. This finding underscores the reliability of these diagnostic markers in small samples and in surgical samples following neoadjuvant chemotherapy, with very few exceptions. A novel finding was the significant diminution in intensity of WT1 staining following chemotherapy.
Authors: Eun Young Kang; Joshua Millstein; Gordana Popovic; Nicola S Meagher; Adelyn Bolithon; Aline Talhouk; Derek S Chiu; Michael S Anglesio; Betty Leung; Katrina Tang; Neil Lambie; Marina Pavanello; Annalyn Da-Anoy; Diether Lambrechts; Liselore Loverix; Siel Olbrecht; Christiani Bisinotto; Jesus Garcia-Donas; Sergio Ruiz-Llorente; Monica Yagüe-Fernandez; Robert P Edwards; Esther Elishaev; Alexander Olawaiye; Sarah Taylor; Beyhan Ataseven; Andreas du Bois; Philipp Harter; Jenny Lester; Claus K Høgdall; Sebastian M Armasu; Yajue Huang; Robert A Vierkant; Chen Wang; Stacey J Winham; Sabine Heublein; Felix K F Kommoss; Daniel W Cramer; Naoko Sasamoto; Lilian van-Wagensveld; Maria Lycke; Constantina Mateoiu; Janine Joseph; Malcolm C Pike; Kunle Odunsi; Chiu-Chen Tseng; Celeste L Pearce; Sanela Bilic; Thomas P Conrads; Arndt Hartmann; Alexander Hein; Michael E Jones; Yee Leung; Matthias W Beckmann; Matthias Ruebner; Minouk J Schoemaker; Kathryn L Terry; Mona A El-Bahrawy; Penny Coulson; John L Etter; Katherine LaVigne-Mager; Juergen Andress; Marcel Grube; Anna Fischer; Nina Neudeck; Greg Robertson; Rhonda Farrell; Ellen Barlow; Carmel Quinn; Anusha Hettiaratchi; Yovanni Casablanca; Ramona Erber; Colin J R Stewart; Adeline Tan; Yu Yu; Jessica Boros; Alison H Brand; Paul R Harnett; Catherine J Kennedy; Nikilyn Nevins; Terry Morgan; Peter A Fasching; Ignace Vergote; Anthony J Swerdlow; Francisco J Candido Dos Reis; G Larry Maxwell; Susan L Neuhausen; Arantzazu Barquin-Garcia; Francesmary Modugno; Kirsten B Moysich; Philip J Crowe; Akira Hirasawa; Florian Heitz; Beth Y Karlan; Ellen L Goode; Peter Sinn; Hugo M Horlings; Estrid Høgdall; Karin Sundfeldt; Stefan Kommoss; Annette Staebler; Anna H Wu; Paul A Cohen; Anna DeFazio; Cheng-Han Lee; Helen Steed; Nhu D Le; Simon A Gayther; Kate Lawrenson; Paul D P Pharoah; Gottfried Konecny; Linda S Cook; Susan J Ramus; Linda E Kelemen; Martin Köbel Journal: Virchows Arch Date: 2021-11-15 Impact factor: 4.535