SFEBES2023 Poster Presentations Neuroendocrinology and Pituitary (74 abstracts)
MGMT and MSH2 immunohistochemistry status identifies a pituitary tumour subgroup with excellent progression free survival response to temozolomide: a single centre case series
Ben Whitelaw 1 , Jackie Gilbert 1 , Ling Ling Chuah 1 , James Crane 1 , Georgios Dimitriadis 1 , Nick Thomas 1 , Sinan Barazi 1 , Eleni Maratos 1 , Jonathan Shapey 1 , Leah Laniba 1 , Nila Lazaro 1 , Nadia Gordon 1 , Omar Al-Salihi 2 , Andrew King 1 , Safa Al-Sarraj 1 , Zita Reisz 1 , Istvan Bodi 1 , Ayisha Al Busaidi 1 , Jean-Marie U-King-IM 1 & Simon Aylwin 1
1King’s College Hospital NHS Foundation Trust, London, United Kingdom. 2Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
Temozolomide has an established role as first line chemotherapy for aggressive pituitary adenoma and carcinoma. There are mixed reports whether the MGMT (methylguanine methyltransferase) and mismatch repair protein (MSH2/6) status of a tumour, assessed by immunohistochemistry (IHC) can predict response to temozolomide. This is the first series to assess combined MGMT and MSH2 status. We analysed a retrospective case series of patients treated with temozolomide at our tertiary pituitary service (2009-2022). We assessed the radiological (RECIST) response to temozolomide treatment and correlated it with the MGMT and MSH2 immunohistochemistry.
Results: 22 patients treated were included in the study. 73% of patients (16/22) had a good radiological response to temozolomide (1 complete response, 14 partial response, 1 stable disease). The remaining 6 patients had progressive disease, 5/6 now deceased. Immunohistochemistry (IHC) MGMT and MSH2 status demonstrates that 10/22 patients were MGMT positive, 16/22 patients were MSH2 positive. Analysis of the subgroup who are MGMT negative and MSH2 positive showed 100% (11/11) good radiological response. Conversely the remaining 11 patients with other IHC profiles show a significantly worse response rate 45% (5/11) (Fisher exact test P=0.0053). The progression free survival analysis (Kaplan-Meier plot) shows significantly better survival for the MGMT negative MSH2 positive group (P<0.001).
| MGMT Negative (<10% IHC) | MGMT Positive (≥10% IHC) | Total | |
| MSH2 Positive (>50%) | 100% response (11/11) | 40% response (2/5) | 16 |
| MSH2 Negative (≤50%) | 0% response (0/1) | 60% response (3/5) | 6 |
| Total | 12 | 10 | 22 |
Conclusion: The case series identifies a pituitary IHC subgroup (MGMT negative, MSH2 positive) expected to show a favourable response to temozolomide. This finding will assist treatment sequencing and timing decisions. Unfavourable IHC profiles may, in future, be offered alternative combination treatments. We recommend that aggressive pituitary tumours have prospective histopathological assessment of MGMT and MSH2/6.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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