Scripties UMCG - Rijksuniversiteit Groningen
 
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Novel insights into pure and mixed clear cell carcinomas in endometrial cancer

(2016) Dijkstra, M.D.

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.





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