Differential transcriptional and protein expression of thyroid-stimulating hormone receptor in ovarian carcinomas.
OBJECTIVE
Thyroid-stimulating hormone (TSH) regulates normal thyroid function by binding to its receptor (thyroid-stimulating hormone receptor -TSHR) that is expressed at the surface of thyroid cells. Recently, it has been demonstrated that TSHR is abundantly expressed in several tissues apart from the thyroid, among them the normal ovarian surface epithelium. The role of TSHR expression outside the thyroid is not completely understood. The current study examines possible alterations of TSHR expression in ovarian carcinomas and its implication in ovarian carcinogenesis.


METHODS
Quantitative real-time polymerase chain reaction and immunohistochemistry analysis of TSHR expression were performed in 34 ovarian carcinoma specimens and 10 normal ovarian tissues (controls).


RESULTS
Significant reduction in TSHR messenger RNA (mRNA) expression was detected in ovarian carcinomas (mean [SD]: 0.518 [0.0934] vs normal, 49.4985 [89.1626]; P < 0.001, Mann-Whitney U test), whereas TSHR protein levels were significantly increased (percentage of positive cells: cancer, 73.55% [20.09%], vs normal, 54.54% [21.14%]; intensity: cancer, 2.52 [0.508], vs normal 1 [0]; P = 0.012, Mann-Whitney U test). No significant differences in TSHR mRNA were found according to history of thyroid disease.


CONCLUSIONS
Our study describes for the first time alterations in TSHR expression both at mRNA and protein levels in ovarian carcinomas. The discrepancy between the decreased levels of the TSHR mRNA and the increased protein expression has already been described in thyroid carcinomas and might be due to alterations in its degradation by the ubiquitin system or other unknown mechanisms. Further analysis could elucidate the role of these findings in ovarian carcinogenesis.
Revekka
R
Gyftaki
*Department of Clinical Therapeutics, Alexandra Hospital, †Department of Cytopathology, Areteion Hospital, ‡Endocrine Unit, Department of Clinical Therapeutics, Alexandra Hospital, and §Department of Obstetrics and Gynecology, Alexandra Hospital, Athens University Medical School, Athens, Greece.
Gyftaki
G
Revekka
Christina
C
Liacos
Liacos
L
Christina
Ekaterini
E
Politi
Politi
P
Ekaterini
Michalis
M
Liontos
Liontos
L
Michalis
Katerina
K
Saltiki
Saltiki
S
Katerina
Theocharis
T
Papageorgiou
Papageorgiou
P
Theocharis
Nikolaos
N
Thomakos
Thomakos
T
Nikolaos
Dimitrios
D
Haidopoulos
Haidopoulos
H
Dimitrios
Alexandros
A
Rodolakis
Rodolakis
R
Alexandros
Maria
M
Alevizaki
Alevizaki
A
Maria
Aristotelis
A
Bamias
Bamias
B
Aristotelis
Athanasios
A
Dimopoulos
Dimopoulos Meletios
DM
Athanasios
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin