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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 Dec; 33(12):1869-77.AJ

Abstract

Endometrial carcinomas (ECs) in young women (< or = 40 y) are usually managed conservatively in selected patients. Whether oophorectomy with total hysterectomy is mandated for patients failing hormonal therapy is controversial. Recognition of features that might discourage conservative management and ovarian preservation are currently poorly characterized. We evaluated these patients for DNA mismatch repair (MMR) protein defects to assess whether the MMR status had an impact on therapeutic decision making. Seventy ECs in women of 40 years of age or younger (n=70) were identified from review of institutional databases (1993-present). All available slides were reviewed and DNA MMR immunohistochemistry was performed using 4 markers (MLH1, PMS2, MSH2, and MSH6) in cases with available blocks (n=54). ECs were predominantly endometrioid (65/70), and most were low grade (1988 International Federation of Gynecology and Obstetrics grades 1 or 2, 83%). Five (7%) were undifferentiated carcinomas. Most patients presented at early stage (stages I to II, 90%). A significant number of patients also had synchronous ovarian carcinomas (9 of 70, 13%), predominantly endometrioid (7 of 9), whereas 2 were ovarian clear cell carcinomas. Sixty-six of the 70 patients are alive with no evidence of disease, whereas 4 patients (6%) died of disease. Immunohistochemistry for DNA MMR showed loss of at least 1 protein in 9 of 54 cases (16%) with slight predominance of MSH2/MSH6 abnormalities (5 of 9) compared with loss of MLH1/PMS2. Tumors with MMR loss frequently occurred in women with low body mass index; these tumors were of higher grade and associated with worse clinical outcomes. They frequently showed tumor characteristics associated with microsatellite instability, including tumor infiltrating lymphocytes, undifferentiated or dedifferentiated histology, and lower uterine segment origin. These tumors also showed lower estrogen receptor/progesterone receptor expression compared with tumors with retained staining for MMR proteins. None of the cases with synchronous ovarian and endometrial endometrioid carcinomas showed loss of MMR proteins, whereas 1 of 2 ECs with synchronous CCC of ovary showed loss of MSH2/MSH6.As young women with endometrioid carcinomas who show loss of mismatch proteins are at risk for high-grade tumors with worse clinical outcomes and lower estrogen receptor/progesterone receptor expression, they may not be appropriate candidates for conservative management. Although young EC patients are at increased risk for synchronous endometrioid ovarian carcinomas, this does not seem to be associated with MMR loss.

Authors+Show Affiliations

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19898223

Citation

Garg, Karuna, et al. "Endometrial Carcinomas in Women Aged 40 Years and Younger: Tumors Associated With Loss of DNA Mismatch Repair Proteins Comprise a Distinct Clinicopathologic Subset." The American Journal of Surgical Pathology, vol. 33, no. 12, 2009, pp. 1869-77.
Garg K, Shih K, Barakat R, et al. 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.
Garg, K., Shih, K., Barakat, R., Zhou, Q., Iasonos, A., & Soslow, R. A. (2009). Endometrial carcinomas in women aged 40 years and younger: tumors associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset. The American Journal of Surgical Pathology, 33(12), 1869-77. https://doi.org/10.1097/PAS.0b013e3181bc9866
Garg K, et al. 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. PubMed PMID: 19898223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endometrial carcinomas in women aged 40 years and younger: tumors associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset. AU - Garg,Karuna, AU - Shih,Karin, AU - Barakat,Richard, AU - Zhou,Qin, AU - Iasonos,Alexia, AU - Soslow,Robert A, PY - 2009/11/10/entrez PY - 2009/11/10/pubmed PY - 2009/12/16/medline SP - 1869 EP - 77 JF - The American journal of surgical pathology JO - Am J Surg Pathol VL - 33 IS - 12 N2 - Endometrial carcinomas (ECs) in young women (< or = 40 y) are usually managed conservatively in selected patients. Whether oophorectomy with total hysterectomy is mandated for patients failing hormonal therapy is controversial. Recognition of features that might discourage conservative management and ovarian preservation are currently poorly characterized. We evaluated these patients for DNA mismatch repair (MMR) protein defects to assess whether the MMR status had an impact on therapeutic decision making. Seventy ECs in women of 40 years of age or younger (n=70) were identified from review of institutional databases (1993-present). All available slides were reviewed and DNA MMR immunohistochemistry was performed using 4 markers (MLH1, PMS2, MSH2, and MSH6) in cases with available blocks (n=54). ECs were predominantly endometrioid (65/70), and most were low grade (1988 International Federation of Gynecology and Obstetrics grades 1 or 2, 83%). Five (7%) were undifferentiated carcinomas. Most patients presented at early stage (stages I to II, 90%). A significant number of patients also had synchronous ovarian carcinomas (9 of 70, 13%), predominantly endometrioid (7 of 9), whereas 2 were ovarian clear cell carcinomas. Sixty-six of the 70 patients are alive with no evidence of disease, whereas 4 patients (6%) died of disease. Immunohistochemistry for DNA MMR showed loss of at least 1 protein in 9 of 54 cases (16%) with slight predominance of MSH2/MSH6 abnormalities (5 of 9) compared with loss of MLH1/PMS2. Tumors with MMR loss frequently occurred in women with low body mass index; these tumors were of higher grade and associated with worse clinical outcomes. They frequently showed tumor characteristics associated with microsatellite instability, including tumor infiltrating lymphocytes, undifferentiated or dedifferentiated histology, and lower uterine segment origin. These tumors also showed lower estrogen receptor/progesterone receptor expression compared with tumors with retained staining for MMR proteins. None of the cases with synchronous ovarian and endometrial endometrioid carcinomas showed loss of MMR proteins, whereas 1 of 2 ECs with synchronous CCC of ovary showed loss of MSH2/MSH6.As young women with endometrioid carcinomas who show loss of mismatch proteins are at risk for high-grade tumors with worse clinical outcomes and lower estrogen receptor/progesterone receptor expression, they may not be appropriate candidates for conservative management. Although young EC patients are at increased risk for synchronous endometrioid ovarian carcinomas, this does not seem to be associated with MMR loss. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/19898223/Endometrial_carcinomas_in_women_aged_40_years_and_younger:_tumors_associated_with_loss_of_DNA_mismatch_repair_proteins_comprise_a_distinct_clinicopathologic_subset_ L2 - https://doi.org/10.1097/PAS.0b013e3181bc9866 DB - PRIME DP - Unbound Medicine ER -