Abstract
Purpose
The presence of disseminated tumor cells (DTC) in the bone marrow of endometrial carcinoma patients has been demonstrated previously. In contrast to breast cancer, no prognostic significance or association with clinicopathological features was revealed for endometrial carcinoma so far. The aim of this study was to investigate DTC in a large patient cohort with in-depth pathology review data available and to study DTC occurrence in the context of L1CAM and long-term disease specific follow-up.
Methods
Patients treated for endometrial carcinoma at the Tuebingen University Women’s hospital between 2003 and 2013 were identified. Cases with previous expert central pathology review including L1CAM immunohistochemistry and bone marrow aspirates available were selected. The presence of DTC and L1CAM expression was studied immunohistochemically.
Results
In 395 cases with a confirmed diagnosis of endometrial carcinoma, bone marrow aspirates were available. DTC were detected in 17.2%. The presence of DTC was independent from tumor histology, grade, lymphovascular space involvement (LVSI), FIGO stage, myoinvasion, L1CAM immunoreactivity, and nodal metastasis. DTC occurred less frequently in cases with a microcystic elongated and fragmented (MELF) pattern of invasion (2.2 vs. 21.8%, p = 0.0003). Disease progression was distributed equally among patients with and without DTC present.
Conclusions
We were able to confirm previous findings of DTC presence in a large well-characterized cohort of endometrial carcinoma patients. DTC are detectable in almost one-fifth of endometrial carcinoma and occur less frequently with a MELF pattern of invasion. Further studies investigating the role of DTC in endometrial carcinoma are warranted.
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References
Baccelli I et al (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31:539–544. doi:10.1038/nbt.2576
Banys M et al (2009) Disseminated tumor cells in bone marrow may affect prognosis of patients with gynecologic malignancies. Int J Gynecol Cancer 19:948–952. doi:10.1111/IGC.0b013e3181a23c4c
Bosse T et al (2014) L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results. Eur J Cancer 50:2602–2610. doi:10.1016/j.ejca.2014.07.014
Braun S et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802. doi:10.1056/NEJMoa050434
Colombo N et al (2016) ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Int J Gynecol Cancer 26:2–30. doi:10.1097/IGC.0000000000000609
Dellinger TH, Smith DD, Ouyang C, Warden CD, Williams JC, Han ES (2016) L1CAM is an independent predictor of poor survival in endometrial cancer—an analysis of The Cancer Genome Atlas (TCGA). Gynecol Oncol 141:336–340. doi:10.1016/j.ygyno.2016.02.003
Ellenson LH, Ronnett B, Soslow RA, Zaino RJ, Kurman RJ (2011) Endometrial carcinoma. Blaustein’s pathology of the female genital tract, 6th edn. doi:10.1007/978-1-4419-0489-8_9
Fehm T et al (2006) Detection of disseminated tumor cells in patients with gynecological cancers. Gynecol Oncol 103:942–947. doi:10.1016/j.ygyno.2006.05.049
Fogel M, Harari A, Muller-Holzner E, Zeimet AG, Moldenhauer G, Altevogt P (2014) A standardized staining protocol for L1CAM on formalin-fixed, paraffin-embedded tissues using automated platforms. Int J Biol Mark 29:180–183. doi:10.5301/jbm.5000055
Gebauer G, Fehm T, Merkle E, Beck EP, Lang N, Jager W (2001) Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up. J Clin Oncol 19:3669–3674. doi:10.1200/JCO.2001.19.16.3669
Geels YP et al (2016) L1CAM expression is related to non-endometrioid histology, and prognostic for poor outcome in endometrioid endometrial carcinoma. Pathol Oncol Res 22:863–868. doi:10.1007/s12253-016-0047-8
Grevenkamp F et al (2017) Second opinion expert pathology in endometrial cancer: potential clinical implications. Int J Gynecol Cancer 27:289–296. doi:10.1097/IGC.0000000000000870
Hertel JD, Huettner PC, Pfeifer JD (2014) Lymphovascular space invasion in microcystic elongated and fragmented (MELF)-pattern well-differentiated endometrioid adenocarcinoma is associated with a higher rate of lymph node metastasis. Int J Gynecol Pathol 33:127–134. doi:10.1097/PGP.0b013e318285657b
Hosseini H et al (2016) Early dissemination seeds metastasis in breast cancer. Nature. doi:10.1038/nature20785
Joehlin-Price AS et al (2017) The microcystic, elongated, and fragmented (MELF) pattern of invasion: a single institution report of 464 consecutive FIGO grade 1 endometrial endometrioid adenocarcinomas. Am J Surg Pathol 41:49–55. doi:10.1097/PAS.0000000000000754
Kommoss F et al (2017) L1CAM: amending the “low-risk” category in endometrial carcinoma. J Cancer Res Clin Oncol 143:255–262. doi:10.1007/s00432-016-2276-3
Murray SK, Young RH, Scully RE (2003) Unusual epithelial and stromal changes in myoinvasive endometrioid adenocarcinoma: a study of their frequency, associated diagnostic problems, and prognostic significance. Int J Gynecol Pathol 22:324–333. doi:10.1097/01.pgp.0000092161.33490.a9
Pavlakis K, Messini I, Vrekoussis T, Panoskaltsis T, Chrysanthakis D, Yiannou P, Voulgaris Z (2011) MELF invasion in endometrial cancer as a risk factor for lymph node metastasis. Histopathology 58:966–973. doi:10.1111/j.1365-2559.2011.03802.x
Pelletier MP, Trinh VQ, Stephenson P, Mes-Masson AM, Samouelian V, Provencher DM, Rahimi K (2017) Microcystic, elongated, and fragmented pattern invasion is mainly associated with isolated tumor cell pattern metastases in International Federation of Gynecology and Obstetrics grade I endometrioid endometrial cancer. Hum Pathol 62:33–39. doi:10.1016/j.humpath.2016.10.023
Sanci M, Gungorduk K, Gulseren V, Karadeniz T, Kocaer M, Gungorduk O, Ozdemir IA (2017) MELF pattern for predicting lymph node involvement and survival in grade I–II endometrioid-type endometrium cancer. Int J Gynecol Pathol. doi:10.1097/PGP.0000000000000370
Stewart CJ, Brennan BA, Leung YC, Little L (2009) MELF pattern invasion in endometrial carcinoma: association with low grade, myoinvasive endometrioid tumours, focal mucinous differentiation and vascular invasion. Pathology 41:454–459
van der Putten LJ et al (2016) L1CAM expression in endometrial carcinomas: an ENITEC collaboration study. Br J Cancer 115:716–724. doi:10.1038/bjc.2016.235
Walter CB et al (2014) Prevalence and prognostic value of disseminated tumor cells in primary endometrial, cervical and vulvar cancer patients. Future Oncol 10:41–48. doi:10.2217/fon.13.174
Zaino RJ (2014) Unusual patterns of endometrial carcinoma including MELF and its relation to epithelial mesenchymal transition. Int J Gynecol Pathol 33:357–364. doi:10.1097/PGP.0000000000000137
Zeimet AG et al (2013) L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation. J Natl Cancer Inst 105:1142–1150. doi:10.1093/jnci/djt144
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Study approval was obtained from the Independent Ethics Committee of the University of Tübingen. All procedures were performed in accordance with the ethical standards of the institutional research committee.
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Kommoss, S., Hartkopf, A.D., Krämer, B. et al. Disseminated tumor cells are not associated with established risk factors, L1CAM immunoreactivity and outcome in endometrial carcinoma. J Cancer Res Clin Oncol 143, 2183–2188 (2017). https://doi.org/10.1007/s00432-017-2474-7
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DOI: https://doi.org/10.1007/s00432-017-2474-7