Abstract
Objective
The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS).
Methods
This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I–IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome.
Results
Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36–2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39–2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08).
Conclusion
In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.
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References
Cantrell LA, Blank SV, Duska LR. Uterine carcinosarcoma: a review of the literature. Gynecol Oncol 2015;137:581–588.
Matsuo K, Ross MS, Machida H, Blake EA, Roman LD. Trends of uterine carcinosarcoma in the United States. J Gynecol Oncol 2018;29:e22.
Matsuo K, Takazawa Y, Ross MS, et al. Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma. Ann Oncol 2016;27:1257–1266.
Morice P, Piovesan P, Rey A, et al. Prognostic value of lymphovascular space invasion determined with hematoxylin-eosin staining in early stage cervical carcinoma: results of a multivariate analysis. Ann Oncol 2003;14:1511–1517.
Roman LD, Felix JC, Muderspach LI, et al. Influence of quantity of lymph-vascular space invasion on the risk of nodal metastases in women with early-stage squamous cancer of the cervix. Gynecol Oncol 1998;68:220–225.
Chernofsky MR, Felix JC, Muderspach LI, et al. Influence of quantity of lymph vascular space invasion on time to recurrence in women with early-stage squamous cancer of the cervix. Gynecol Oncol 2006;100:288–293.
Pol FJ, Zusterzeel PL, van Ham MA, Kuijpers DA, Bulten J, Massuger LF. Satellite lymphovascular space invasion: An independent risk factor in early stage cervical cancer. Gynecol Oncol 2015;138:579–584.
Bosse T, Peters EE, Creutzberg CL, et al. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer—a pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer 2015;51:1742–1750.
Matsuo K, Garcia-Sayre J, Medeiros F, et al. Impact of depth and extent of lymphovascular space invasion on lymph node metastasis and recurrence patterns in endometrial cancer. J Surg Oncol 2015;112:669–676.
Guntupalli SR, Zighelboim I, Kizer NT, et al. Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer. Gynecol Oncol 2012;124:31–35.
Matsuo K, Yessaian AA, Lin YG, et al. Predictive model of venous thromboembolism in endometrial cancer. Gynecol Oncol 2013;128:544–551.
Matsuo K, Sheridan TB, Yoshino K, et al. Significance of lymphovascular space invasion in epithelial ovarian cancer. Cancer Med 2013;1:156–164.
Matsuo K, Yoshino K, Hiramatsu K, et al. Effect of lymphovascular space invasion on survival of stage I epithelial ovarian cancer. Obstet Gynecol 2014;123:957–965.
Matsuo K, Sheridan TB, Mabuchi S, et al. Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma. Gynecol Oncol 2014;133:473–479.
Matsuo K, Yoshino K, Hasegawa K, et al. Survival outcome of stage I ovarian clear cell carcinoma with lympho-vascular space invasion. Gynecol Oncol 2015;136:198–204.
Matsuo K, Wong KK, Fotopoulou C, et al. Impact of lympho-vascular space invasion on tumor characteristics and survival outcome of women with low-grade serous ovarian carcinoma. J Surg Oncol 2018;117(2):236–244.
Creasman WT, Ali S, Mutch DG, et al. Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG oncology/gynecologic oncology group study on GOG-210 protocol. Gynecol Oncol 2017;145:519–525.
Altman AD, Ferguson SE, Atenafu EG, et al. Canadian high risk endometrial cancer (CHREC) consortium: analyzing the clinical behavior of high risk endometrial cancers. Gynecol Oncol 2015;139:268–274.
Harano K, Hirakawa A, Yunokawa M, et al. Prognostic factors in patients with uterine carcinosarcoma: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group. Int J Clin Oncol 2015;21:168–176.
Cantrell LA, Havrilesky L, Moore DT, et al. A multi-institutional cohort study of adjuvant therapy in stage I–II uterine carcinosarcoma. Gynecol Oncol 2012;127:22–26.
Wada H, Enomoto T, Fujita M, et al. Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res 1997;57:5379–5385.
Cherniack AD, Shen H, Walter V, et al. Integrated Molecular Characterization of Uterine Carcinosarcoma. Cancer Cell 2017;31:411–423.
Zhao S, Bellone S, Lopez S, et al. Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial-mesenchymal transition. Proc Natl Acad Sci USA 2016;113:12238–12243.
Ferguson SE, Tornos C, Hummer A, Barakat RR, Soslow RA. Prognostic features of surgical stage I uterine carcinosarcoma. Am J Surg Pathol 2007;31:1653–1661.
Abdulfatah E, Lordello L, Khurram M, et al. Predictive histologic factors in carcinosarcomas of the uterus: a multiinstitutional study. Int J Gynecol Pathol. Epub 3 Apr 2018. https://doi.org/10.1097/pgp.0000000000000497.
Matsuo K, Ross MS, Bush SH, et al. Tumor characteristics and survival outcomes of women with tamoxifen-related uterine carcinosarcoma. Gynecol Oncol 2017;144:329–335.
Matsuo K, Omatsu K, Ross MS, et al. Impact of adjuvant therapy on recurrence patterns in stage I uterine carcinosarcoma. Gynecol Oncol 2017;145:78–87.
Matsuo K, Johnson MS, Im DD, et al. Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery. J Surg Oncol 2018;117(3):488–496.
Matsuo K, Ross MS, Yunokawa M, et al. Salvage chemotherapy with taxane and platinum for women with recurrent uterine carcinosarcoma. Gynecol Oncol 2017;147:565–571.
Matsuo K, Ross MS, Im DD, et al. Significance of venous thromboembolism in women with uterine carcinosarcoma. Gynecol Oncol 2018;148(2):267–274.
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 2007;335:806–808.
Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009;105:103–104.
Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. J Am Stat Assoc 1958;53:457–481.
Cox DR. Regression models and life-tables. J R Stat Soc Series B Stat Methodol 1972;34:187–220.
Mansfield ER, Helms BP. Detecting multicollinearity. Am Stat 1982;36:158–160.
Rauh-Hain JA, Oduyebo T, Diver EJ, et al. Uterine leiomyosarcoma: an updated series. Int J Gynecol Cancer 2013;23:1036–1043.
Wang WL, Soslow R, Hensley M, et al. Histopathologic prognostic factors in stage I leiomyosarcoma of the uterus: a detailed analysis of 27 cases. Am J Surg Pathol 2011;35:522–529.
Roma AA, Barbuto DA, Samimi SA, et al. Vascular invasion in uterine sarcomas and its significance. A multi-institutional study. Hum Pathol 2015;46:1712–1721.
Dos Santos LA, Garg K, Diaz JP, et al. Incidence of lymph node and adnexal metastasis in endometrial stromal sarcoma. Gynecol Oncol 2011;121:319–322.
Hensley ML. Role of chemotherapy and biomolecular therapy in the treatment of uterine sarcomas. Best Pract Res Clin Obstet Gynaecol 2011;25:773–782.
Sampath S, Gaffney DK. Role of radiotherapy treatment of uterine sarcoma. Best Pract Res Clin Obstet Gynaecol 2011;25:761–772.
Ducie JA, Leitao MM, Jr. The role of adjuvant therapy in uterine leiomyosarcoma. Expert Rev Anticancer Ther 2015;16:45–55.
Funding
This study was supported by the Ensign Endowment for Gynecologic Cancer Research (KM).
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Matsuo, K., Takazawa, Y., Ross, M.S. et al. Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma. Ann Surg Oncol 25, 2756–2766 (2018). https://doi.org/10.1245/s10434-018-6547-x
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DOI: https://doi.org/10.1245/s10434-018-6547-x