Immunophenotypic features of dedifferentiated endometrial carcinoma - insights from BRG1/INI1-deficient tumours.
AIMS
Dedifferentiated endometrial carcinoma (DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 (BRG1) and inactivation of SMARCB1 (INI1) were recently described as potential mechanisms underlying the histological dedifferentiation. The aim of this study was to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histological and molecular features (BRG1/INI1 deficiency).


METHODS AND RESULTS
We evaluated PAX8, oestrogen receptor (ER) and p53 immunostaining in the endometrioid and the undifferentiated components of 20 BRG1/INI1-deficient DDECs and 15 BRG1/INI1-intact DDECs, and compared the results with those of 23 grade 3 endometrioid carcinomas. The differentiated endometrioid component was positive for PAX8 and/or ER in 19 of 20 BRG1/INI1-deficient DDECs, whereas the corresponding undifferentiated component of all 20 tumours showed a complete absence of PAX8 and ER staining. All except one of the BRG1/INI1-deficient tumours showed a wild-type p53 staining pattern. PAX8 and ER expression in the undifferentiated component was absent in 67% and 80% of BRG1/INI1-intact DDECs, respectively, whereas 47% of the BRG1/INI1-intact DDECs showed a mutated p53 staining pattern. In comparison, absent PAX8 expression and absent ER expression were each observed in the more solid area of 48% and 48% of grade 3 endometrioid carcinomas.


CONCLUSIONS
The consistent absence of PAX8 and ER expression in molecularly defined (BRG1/INI1-deficient) DDECs suggests that the loss of PAX8 and ER expression is a fundamental feature of dedifferentiation. The frequent findings of a mutated p53 staining pattern in BRG1/INI1-intact DDECs indicate that BRG1/INI1-intact DDECs may be biologically different from BRG1/INI1-deficient tumours.
['Hoang|Lien N|LN|', 'Lee|Yow-Shan|YS|', 'Karnezis|Anthony N|AN|', 'Tessier-Cloutier|Basile|B|', 'Almandani|Noorah|N|', 'Coatham|Mackenzie|M|', 'Gilks|C Blake|CB|', 'Soslow|Robert A|RA|', 'Stewart|Colin J R|CJ|', 'Köbel|Martin|M|', 'Lee|Cheng-Han|CH|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D014408:Biomarkers, Tumor D018269:Carcinoma, Endometrioid D054337:Cell Dedifferentiation D004265:DNA Helicases D016889:Endometrial Neoplasms D005260:Female D006801:Humans D007150:Immunohistochemistry D016130:Immunophenotyping D008875:Middle Aged D009687:Nuclear Proteins D000072636:PAX8 Transcription Factor D011960:Receptors, Estrogen D000071796:SMARCB1 Protein D014157:Transcription Factors D016159:Tumor Suppressor Protein p53
BRG1 undifferentiated carcinoma SMARCA4 SMARCB1 INI1 PAX8 dedifferentiated carcinoma endometrial cancer