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Association of mismatch repair deficiency in endometrial cancer with 18F-FDG PET/CT and clinicopathological features and their prognostic value

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A Letter to the Editor to this article was published on 27 November 2023

Abstract

Purpose

Identification of the mismatch repair (MMR) deficiency in endometrial cancer (EC) may aid in the screening of patients who may benefit from immunotherapy. Our goal was to investigate the relationship between MMR status and 18F-FDG PET/CT metabolic parameters and clinicopathological features in patients with EC, as well as to explore their prognostic value.

Methods

This retrospective study included 106 EC patients who were classified as MMR deficient (dMMR) or MMR proficient (pMMR) group based on MMR protein expression status evaluated by immunohistochemistry. Clinicopathological characteristics and PET metabolic parameters were compared between the dMMR and pMMR groups, and their relationships with MMR status and prognosis were evaluated.

Results

Of 106 EC patients, 30 patients (28.1%) had dMMR, while 76 (71.7%) had pMMR. Compared with the pMMR group, the dMMR group showed a lower prevalence of overweight (BMI ≥ 25) (17.2% vs. 43.9%, P = 0.019) and more lymph vascular space invasion (43.3% vs. 21.1%, P = 0.029). Although no relationship between glucometabolism parameters and MMR status was observed in all enrolled patients, higher SUVmax was observed in the endometrioid type of EC with MMR deficiency (P = 0.047). Additionally, SUVmax related to MMR status was found in EC patients with advanced FIGO stage (P = 0.026) or deep myometrial invasion (P = 0.026). Multivariate Cox regression analysis revealed that lymph node metastasis was independently predictive of PFS, while advanced FIGO stage was an independent predictor of OS. No significant association between MMR status and prognosis was found in EC.

Conclusion

Higher SUVmax was associated with MMR deficiency in EC patients with endometrioid type, advanced stage, or deep myometrial invasion, which may be useful for predicting the MMR status and thus aiding in determination of immunotherapy for patients with EC.

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Data availability

Data are available based on the reasonable request to the corresponding author.

References

  1. Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet. 2022;399(10333):1412–28.

    Article  PubMed  Google Scholar 

  2. Brooks RA, Fleming GF, Lastra RR, Lee NK, Moroney JW, Son CH, et al. Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 2019;69(4):258–79.

    Article  PubMed  Google Scholar 

  3. Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.

    Article  PubMed  Google Scholar 

  4. Black D, Soslow RA, Levine DA, Tornos C, Chen SC, Hummer AJ, et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol. 2006;24(11):1745–53.

    Article  CAS  PubMed  Google Scholar 

  5. Latham A, Srinivasan P, Kemel Y, Shia J, Bandlamudi C, Mandelker D, et al. Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer. J Clin Oncol. 2019;37(4):286–95.

    Article  CAS  PubMed  Google Scholar 

  6. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cho KR, Cooper K, Croce S, Djordevic B, Herrington S, Howitt B, et al. International Society of Gynecological Pathologists (ISGyP) Endometrial Cancer Project: Guidelines From the Special Techniques and Ancillary Studies Group. Int J Gynecol Pathol. 2019;38(Suppl 1):S114–22.

    Article  PubMed  Google Scholar 

  8. Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol. 2002;20(4):1043–8.

    Article  CAS  PubMed  Google Scholar 

  9. Piñol V, Castells A, Andreu M, Castellví-Bel S, Alenda C, Llor X, et al. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005;293(16):1986–94.

    Article  PubMed  Google Scholar 

  10. Zheng J, Huang B, Nie X, Zhu Y, Han N, Li Y. The clinicopathological features and prognosis of tumor MSI in East Asian colorectal cancer patients using NCI panel. Future Oncol. 2018;14(14):1355–64.

    Article  CAS  PubMed  Google Scholar 

  11. Bollineni VR, Ytre-Hauge S, Bollineni-Balabay O, Salvesen HB, Haldorsen IS. High diagnostic value of 18F-FDG PET/CT in endometrial cancer: systematic review and meta-analysis of the literature. J Nucl Med. 2016;57(6):879–85.

    Article  CAS  PubMed  Google Scholar 

  12. Ghooshkhanei H, Treglia G, Sabouri G, Davoodi R, Sadeghi R. Risk stratification and prognosis determination using (18)F-FDG PET imaging in endometrial cancer patients: a systematic review and meta-analysis. Gynecol Oncol. 2014;132(3):669–76.

    Article  PubMed  Google Scholar 

  13. Lee SS, Choi SJ, Park JS. Correlations among KRAS Mutation, Microsatellite Instability, and 18F-FDG Uptake in Colon Cancer. Asian Pac J Cancer Prev. 2022;23(10):3501–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Llobet D, Pallares J, Yeramian A, Santacana M, Eritja N, Velasco A, et al. Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J Clin Pathol. 2009;62(9):777–85.

    Article  CAS  PubMed  Google Scholar 

  15. Bonneville R, Krook MA, Kautto EA, Miya J, Wing MR, Chen HZ, et al. Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017;2017:PO.17.00073.

    PubMed  Google Scholar 

  16. Diaz-Padilla I, Romero N, Amir E, Matias-Guiu X, Vilar E, Muggia F, et al. Mismatch repair status and clinical outcome in endometrial cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2013;88(1):154–67.

    Article  PubMed  Google Scholar 

  17. Fountzilas E, Kotoula V, Pentheroudakis G, Manousou K, Polychronidou G, Vrettou E, et al. Prognostic implications of mismatch repair deficiency in patients with nonmetastatic colorectal and endometrial cancer. ESMO Open. 2019;4(2):e000474.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Grzankowski KS, Shimizu DM, Kimata C, Black M, Terada KY. Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression. Gynecol Oncol. 2012;126(3):408–12.

    Article  PubMed  Google Scholar 

  19. Pina A, Wolber R, McAlpine JN, Gilks B, Kwon JS. Endometrial cancer presentation and outcomes based on mismatch repair protein expression from a population-based Study. Int J Gynecol Cancer. 2018;28(8):1624–30.

    Article  PubMed  Google Scholar 

  20. Shih KK, Garg K, Levine DA, Kauff ND, Abu-Rustum NR, Soslow RA, et al. Clinicopathologic significance of DNA mismatch repair protein defects and endometrial cancer in women 40years of age and younger. Gynecol Oncol. 2011;123(1):88–94.

    Article  CAS  PubMed  Google Scholar 

  21. Garg K, Shih K, Barakat R, Zhou Q, Iasonos A, Soslow RA. Endometrial carcinomas in women aged 40 years and younger: tumors associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset. Am J Surg Pathol. 2009;33(12):1869–77.

    Article  PubMed  Google Scholar 

  22. Nakamura K, Kodama J, Okumura Y, Hongo A, Kanazawa S, Hiramatsu Y. The SUVmax of 18F-FDG PET correlates with histological grade in endometrial cancer. Int J Gynecol Cancer. 2010;20(1):110–5.

    Article  PubMed  Google Scholar 

  23. Vural Topuz Ö, Aksu A, Erinç SR, Tokgözoğlu N, Tamam M. The evaluation of preoperative (18)F-FDG PET/CT in patients with endometrial cancer and the correlation between pet parameters and postoperative pathology results. Mol Imaging Radionucl Ther. 2022;31(1):16–22.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Arora S, Balasubramaniam S, Zhang W, Zhang L, Sridhara R, Spillman D, et al. FDA approval summary: pembrolizumab plus lenvatinib for endometrial carcinoma, a collaborative international review under project orbis. Clin Cancer Res. 2020;26(19):5062–7.

    Article  CAS  PubMed  Google Scholar 

  25. Di Dio C, Bogani G, Di Donato V, Cuccu I, Muzii L, Musacchio L, et al. The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma. Gynecol Oncol. 2023;169:27–33.

    Article  PubMed  Google Scholar 

  26. O’Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus AA, et al. Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: results from the KEYNOTE-158 Study. J Clin Oncol. 2022;40(7):752–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Antill Y, Kok PS, Robledo K, Yip S, Cummins M, Smith D, et al. Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial. J Immunother Cancer. 2021;9(6):e002255.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Song J, Li Z, Yang L, Wei M, Yang Z, Wang X. Metabolic activity via (18)F-FDG PET/CT is predictive of microsatellite instability status in colorectal cancer. BMC Cancer. 2022;22(1):808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Victoor J, Borght SV, Spans L, Lehnert S, Brems H, Laenen A, et al. Comprehensive immunomolecular profiling of endometrial carcinoma: a tertiary retrospective study. Gynecol Oncol. 2021;162(3):694–701.

    Article  CAS  PubMed  Google Scholar 

  30. Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, et al. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211(5):781–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–32.

    Article  CAS  PubMed  Google Scholar 

  32. Cohn DE, Frankel WL, Resnick KE, Zanagnolo VL, Copeland LJ, Hampel H, et al. Improved survival with an intact DNA mismatch repair system in endometrial cancer. Obstet Gynecol. 2006;108(5):1208–15.

    Article  CAS  PubMed  Google Scholar 

  33. McMeekin DS, Tritchler DL, Cohn DE, Mutch DG, Lankes HA, Geller MA, et al. Clinicopathologic significance of mismatch repair defects in endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol. 2016;34(25):3062–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kato M, Takano M, Miyamoto M, Sasaki N, Goto T, Tsuda H, et al. DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers. J Gynecol Oncol. 2015;26(1):40–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the fund from the National Natural Science Foundation of China (81971645), Guangdong Provincial People's Hospital (KY0120211130), and Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (2022B1212010011).

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Author notes

  1. Xiaolin Sun, Xinchao Yao and Baozhen Zeng have equally contributed to this work.

Authors and Affiliations

  1. PET Center, Department of Nuclear Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Er Road, Guangzhou, 510080, China

    Xiaolin Sun, Xinchao Yao, Linbo Zhu, Yuxiang Shang, Qing Zhang, Li He & Lei Jiang

  2. Department of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

    Baozhen Zeng

  3. Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China

    Lei Jiang

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  1. Xiaolin Sun
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Sun, X., Yao, X., Zeng, B. et al. Association of mismatch repair deficiency in endometrial cancer with 18F-FDG PET/CT and clinicopathological features and their prognostic value. Ann Nucl Med 37, 655–664 (2023). https://doi.org/10.1007/s12149-023-01869-2

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