Abstract
Purpose
The genetic characteristics and mismatch repair (MMR) status of the primary tumor and corresponding metastases in colorectal cancer (CRC) are generally considered to be highly concordant. This implies that either the primary or metastatic tumor can be used for testing gene mutation and MMR status. However, whether this is also true for CRC and their ovarian metastases is currently unknown. Ovarian metastases generally show a poorer response to systemic therapy compared to other metastatic sites. Differences in biomarker status between primary CRC and ovarian metastases could possibly explain this difference in therapy response.
Methods
The study cohort was selected from CRC patients treated in two Dutch hospitals. Eligible patients with CRC and ovarian metastasis who were surgically treated between 2011 and 2018 were included. CRC and corresponding ovarian metastatic tissues were paired. Gene mutation status was established using next-generation sequencing, while the MMR status was established using either immunohistochemistry or microsatellite instability analysis.
Results
Matched samples of CRC and ovarian metastasis from 26 patients were available for analysis. A biomarker concordance of 100% was detected.
Conclusion
Complete biomarker concordance was found between MMR proficient CRC and their matching ovarian metastasis. Biomarker testing of MMR proficient CRC tissue appears to be sufficient, and additional testing of metastatic ovarian tissue is not necessary. Differences in therapy response between ovarian metastases and other metastases from CRC are thus unlikely to be caused by differences in the genetic status.
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Data availability
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
References
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D et al (2020) Pembrolizumab in microsatellite-instability–high advanced colorectal cancer. N Eng J Med 383(23):2207–2218. https://doi.org/10.1056/nejmoa2017699
Banerjee S, Kapur S, Moran BJ (2005) The role of prophylactic oophorectomy in women undergoing surgery for colorectal cancer. Color Dis 7(3):214–217. https://doi.org/10.1111/j.1463-1318.2005.00770.x
Bhullar DS, Barriuso MJS, Saunders MP, O’Dwyer ST, Aziz O (2019) Biomarker concordance between primary colorectal cancer and its metastases. EBioMedicine 40:363–374. https://doi.org/10.1016/j.ebiom.2019.01.050
Brannon AR, Vakiani E, Brooke BES, Scott SN, McDermott G, Shah RH et al (2014) Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. Genome Biol 15(8):1–10. https://doi.org/10.1186/s13059-014-0454-7
Cervantes A, Adam R, Roselló S, Arnold D, Normanno N, Taïeb J, Seligmann J et al (2022) Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol S0923–7534(22):04192–04198. https://doi.org/10.1016/j.annonc.2022.10.003
Crobach S, Ruano D, van Eijk R, Schrumpf M, Fleuren G, van Wezel T, Morreau H (2016) Somatic mutation profiles in primary colorectal cancers and matching ovarian metastases: identification of driver and passenger mutations. J Pathol Clin Res 2(3):166–174. https://doi.org/10.1002/cjp2.45
Dabir PD, Bruggeling CE, van der Post RS, Dutilh BE, Hoogerbrugge N, Ligtenberg MJL, Boleij A et al (2020) Microsatellite instability screening in colorectal adenomas to detect lynch syndrome patients? A systematic review and meta-analysis. Eur J Hum Genet 28(3):277–286. https://doi.org/10.1038/s41431-019-0538-7
Fujiyoshi K, Yamamoto G, Takahashi A, Arai Y, Yamada M, Kakuta M, Yamaguchi K et al (2017) High concordance rate of KRAS/BRAF mutations and MSI-H between primary colorectal cancer and corresponding metastases. Oncol Rep 37(2):785–792. https://doi.org/10.3892/or.2016.5323
Garrett CR, George B, Viswanathan C, Bhadkamkar NA, Wen S, Baladandayuthapani V, You YN et al (2012) Survival benefit associated with surgical oophorectomy in patients with colorectal cancer metastatic to the ovary. Clin Colorectal Cancer 11(3):191–194. https://doi.org/10.1016/j.clcc.2011.12.003
Goéré D, Daveau C, Elias D, Boige V, Tomasic G, Bonnet S, Pocard M et al (2008) The differential response to chemotherapy of ovarian metastases from colorectal carcinoma. Eur J Surg Oncol 34(12):1335–1339. https://doi.org/10.1016/j.ejso.2008.03.010
Hanna NN, Cohen AM (2004) Ovarian neoplasms in patients with colorectal cancer: understanding the role of prophylactic oophorectomy. Clin Colorectal Cancer 3(4):215–222. https://doi.org/10.3816/CCC.2004.n.002
He WZ, Hu WM, Wang F, Rong YM, Yang L, Xie QK, Yang YZ et al (2019) Comparison of mismatch repair status between primary and matched metastatic sites in patients with colorectal cancer. JNCCN J Natl Compr Cancer Netw 17(10):1174–1183. https://doi.org/10.6004/jnccn.2019.7308
Kim DD, Park IJ, Kim HC, Yu CS, Kim JC (2009) Ovarian metastases from colorectal cancer: a clinicopathological analysis of 103 patients. Color Dis 11(1):32–38. https://doi.org/10.1111/j.1463-1318.2008.01543.x
Kim MJ, Lee HS, Kim JH, Kim YJ, Kwon JH, Lee JO, Bang SM et al (2012) Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer. BMC Cancer 12:347. https://doi.org/10.1186/1471-2407-12-347
Kim R, Schell MJ, Teer JK, Greenawalt DM, Yang M, Yeatman TJ (2015) Co-evolution of somatic variation in primary and metastatic colorectal cancer may expand biopsy indications in the molecular era. PLoS ONE 10(5):1–12. https://doi.org/10.1371/journal.pone.0126670
Lee SJ, Lee J, Lim HY, Kang WK, Choi CH, Lee JW, Kim TJ et al (2010) Survival benefit from ovarian metastatectomy in colorectal cancer patients with ovarian metastasis: a retrospective analysis. Cancer Chemother Pharmacol 66(2):229–235. https://doi.org/10.1007/s00280-009-1150-2
Mao C, Wu WY, Yang ZY, Threapleton DE, Yuan JQ, Yu YY, Tang JL (2015) Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases. Sci Rep 5:8065. https://doi.org/10.1038/srep08065
Mori Y, Nyuya A, Yasui K, Toshima T, Kawai T, Taniguchi F, Kimura K et al (2018) Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles. Oncotarget 9(23):16477–16488
Morrow M (1984) Late ovarian metastases in carcinoma of the colon and rectum. Arch of Surg 119(12):1385. https://doi.org/10.1001/archsurg.1984.01390240023004
“My Cancer Genome.” n.d. Accessed June 14, 2022. https://www.mycancergenome.org/
Olivier M, Hollstein M, Hainaut P (2010) TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2(1):1–18. https://doi.org/10.1101/cshperspect.a001008
Paramythiotis D, Goulas P, Moysidis M, Karakatsanis A, Tzioufa-Asimakopoulou V, Sotiriou S, Michalopoulos A (2019) Metachronous ovarian metastases in a patient with primary colorectal cancer. A case report and review of the literature. Am J Case Rep 20:1515–1520. https://doi.org/10.12659/AJCR.917957
Park S, Ahn HK, Lee DH, Jung YJ, Jeong JW, Nam S, Lee WS (2019) Systematic mutation analysis in rare colorectal cancer presenting ovarian metastases. Sci Rep 9(1):1–10. https://doi.org/10.1038/s41598-019-53182-6
Segelman J, Floter-Radestad A, Hellborg H, Sjovall A, Martling A (2010) Epidemiology and prognosis of ovarian metastases in colorectal cancer. Br J Surg 97(11):1704–1709. https://doi.org/10.1002/bjs.7196
Sekine K, Hamaguchi T, Shoji H, Takashima A, Honma Y, Iwasa S, Kato K et al (2018) Retrospective analyses of systemic chemotherapy and cytoreductive surgery for patients with ovarian metastases from colorectal cancer: a single-center experience. Oncology 95(4):220–228. https://doi.org/10.1159/000489665
Sweeney SM, Cerami E, Baras A, Pugh TJ, Schultz N, Stricker T, Lindsay J et al (2017) AACR project genie: powering precision medicine through an international consortium. Cancer Discov 7(8):818–831. https://doi.org/10.1158/2159-8290.CD-17-0151
Taylor AE, Nicolson VMC, Cunningham D (1995) Ovarian metastases from primary gastrointestinal malignancies: the royal Marsden hospital experience and implications for adjuvant treatment. Br J Cancer 71(1):92–96. https://doi.org/10.1038/bjc.1995.18
Thabet A, Somarouthu B, Oliva E, Gervais DA, Hahn PF, Lee SI (2014) Image-guided ovarian mass biopsy: efficacy and safety. J Vasc Interv Radiol 25(12):1922-1927.e1. https://doi.org/10.1016/j.jvir.2014.08.009
Tong G, Luo Q, Pang X, Chen B, Lv G, Li X, Wang S (2021) Retrospective analyses of complete resection combined with systemic chemotherapy and targeted therapy for patients with ovarian metastases from colorectal cancer. Cancer Biothe Radiopharm 00(00):1–7. https://doi.org/10.1089/cbr.2020.4013
Ursem CJ, Zhou M, Paciorek AT, Atreya CE, Ko AH, Zhang L, van Loon K (2020) Clinicopathologic characteristics and impact of oophorectomy for ovarian metastases from colorectal cancer. Oncologist 25(7):564–571. https://doi.org/10.1200/jco.2018.36.4_suppl.779
van der Meer R, Bakkers C, Rostamkhan E, de Hingh I, Roumen R (2021) Ovarian metastases from colorectal cancer in young women: a systematic review of the literature. Int J Colorectal Dis 36(12):2567–2575. https://doi.org/10.1007/s00384-021-04012-7
van Morris K, Kennedy EB, Baxter NN, Benson AB, Cercek A, Cho M, Ciombor KK et al (2022) Treatment of Metastatic Colorectal Cancer: ASCO Guideline. J Clin Oncol. https://doi.org/10.1200/JCO.22.01690
Wright JD, Powell MA, Mutch DG, Rader JS, Gibb RK, Huettner PC, Herzog TJ, Fujiwara K (2004) Synchronous ovarian metastases at the time of laparotomy for colon cancer. Women’s Oncol Rev 4(2):109–110. https://doi.org/10.1080/1473340410001732442
Zou Y, Hu X, Zheng S, Yang A, Li X, Tang H, Kong Y, Xie X (2021) Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: a multidimensional analysis. EBioMedicine. https://doi.org/10.1016/j.ebiom.2020.103137
Funding
This study and all the analyses were funded by a grant from ‘Commissie Onderzoek en Innovatie’ (COI) of the Máxima Medical Center.
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The work reported in the paper has been performed by all the authors. Furthermore, RM, JJ, SB, and RR made substantial conceptual and design contributions and analyzed important data. All the authors reviewed the manuscript.
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The regional Medical Research Ethics Committee of the Máxima Medical Center approved this study (protocol number: 2021-MMC-022) and confirmed that the Medical Research Involving Human Subjects Act (WMO) did not apply. The study was also approved by the institutional review boards of the Catharina Cancer Institute and the national archive of pathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief, PALGA).
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van der Meer, R., Jeuken, J.W.M., Bosch, S.L. et al. Biomarker concordance between primary colorectal cancer and ovarian metastases: a Dutch cohort study. J Cancer Res Clin Oncol 149, 5677–5685 (2023). https://doi.org/10.1007/s00432-022-04502-3
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DOI: https://doi.org/10.1007/s00432-022-04502-3