Novel insights into pure and mixed clear cell carcinomas in endometrial cancer

Dijkstra, M.D. (2016) Novel insights into pure and mixed clear cell carcinomas in endometrial cancer. thesis, Medicine.

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Abstract

background Endometrial clear cell carcinoma (CCC) and mixed endometrioid carcinoma with a clear cell component (EEC-CC) are rare forms of endometrial carcinoma (EC). Traditionally, these tumors are classified and treated as high grade tumors. However, just a few studies have identified clinical outcome for patients with pure CCCs and little is known about the overall survival of the mixed carcinomas. Also, the predictive value of pipelle in subtyping these tumors has not yet been determined. Lastly, determining an immunoprofile of these tumors could bring new insights in the pathogenesis of these tumors and be of potential diagnostic aid. methods We selected and revised 51 pure CCCs and 28 mixed EEC-CC cases diagnosed since 1980 in the UMCG and Isala Zwolle. Clinical outcome of these patients were compared to each other. We also selected these patients for determining the positive predictive value of pipelle compared to the definitive diagnosis on hysterectomy. Immunohistochemical staining for ER, PR, PTEN, p53, HNF1-β, Napsin A, AMACR, p16 and MMR, which are common markers used for CCC and endometrioid carcinoma, were performed on all pure CCC and both components of the mixed carcinomas to obtain an immunoprofile of these tumors. results We found an overall 5-year survival rate of 64% for CCC, compared to 68% for mixed EEC-CC, which was not statistically significant. The positive predictive value of pipelle for detecting a pure CCC is 100%, compared to 50% for a mixed EEC-CCC. We found the immunophenotype of ER– and PR– (71.8-95.2% resp. 87.5-92.9%), HNF1-β+ (61.9-91.7%) to be most common in all pure CCC cases. Loss of PTEN expression, a p53 mutation and positive Napsin A was present in about 50% of all CCC and AMACR immunoreactivity was present in 33%. For mixed carcinomas ER, PR and HNF1- β expression significantly differed in expression between the endometrioid and clear cell component. The clear cell component of the mixed tumor did show a significant lower expression for HNF1-β and Napsin A compared to a pure CCC. Microsatellite instability for MSH2/MSH6 was also significantly higher for mixed carcinomas compared to pure CCC. conclusion The outcome of mixed carcinoma is not significantly different from a pure CCC, despite the presence of a low-grade endometrioid component. Also, pipelle is highly predictive for detecting a pure CCC, while correctly diagnosing just half of all mixed carcinomas. An immunoprofile of loss of ER, PR and positive HNF1-β was most common in CCC of our study. Furthermore, the immunoprofile of the CC component in mixed EEC-CC is intermediate between pure CCC and EEC, suggesting a common pre-existing endometrioid lesion from which the clear cell component originates.

Item Type:	Thesis (Thesis)
Supervisor name:	supervisors UMCG and Hollema, prof. dr. H. and Bart, dr. J. and Department of Pathology
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:46
Last Modified:	25 Jun 2020 10:46
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/702

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