Immunophenotypic features of dedifferentiated endometrial carcinoma - insights from BRG1/INI1-deficient tumours.
OBJECTIVE
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).


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.
Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.|Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Lien N
LN
Hoang
Department of Family Medicine, Cathay General Hospital, Taipei, Taiwan.
Yow-Shan
YS
Lee
Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
Anthony N
AN
Karnezis
Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
Basile
B
Tessier-Cloutier
Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
Noorah
N
Almandani
Department of Oncology, University of Alberta, Edmonton, Canada.
Mackenzie
M
Coatham
Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
C Blake
CB
Gilks
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Robert A
RA
Soslow
Department of Histopathology, King Edward Memorial Hospital and School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia.
Colin J R
CJ
Stewart
Department of Pathology and Laboratory Medicine, Calgary Laboratory Services and University of Calgary, Calgary.
Martin
M
Köbel
Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital and University of Alberta, Edmonton, AB, Canada. chlee2@ualberta.ca.
Cheng-Han
CH
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018269:Carcinoma, Endometrioid / Q000473:pathology*; D054337:Cell Dedifferentiation; D004265:DNA Helicases / Q000172:deficiency*; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008875:Middle Aged; D009687:Nuclear Proteins / Q000172:deficiency*; D000072636:PAX8 Transcription Factor / Q000032:analysis / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis; D000071796:SMARCB1 Protein / Q000172:deficiency*; D014157:Transcription Factors / Q000172:deficiency*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D011960:Receptors, Estrogen; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C084108:SMARCA4 protein, human; D004265:DNA Helicases
BRG1; INI1; PAX8; SMARCA4; SMARCB1; dedifferentiated carcinoma; endometrial cancer; undifferentiated carcinoma