NOTCH2expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype.
BACKGROUND
Notch family members function as both oncogenes and tumor suppressors.NOTCH2is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival.NOTCH2has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern ofNOTCH2in ovarian cancer is unknown.


METHODS
An immunohistochemical analysis using a polyclonal antibody to theNOTCH2intracellular domain was performed on a total of 119 ovarian carcinomas, and 7 serous borderline tumors, arranged onto tissue arrays. Normal ovarian and fallopian tube epithelium were used as controls. Specimens were scored as low or highNOTCH2expression. The score distributions for the subtypes were analyzed with the chi square test.


RESULTS
Fifty two of 61 (85.2%) papillary serous, eight of 13 (61.5%) clear cell, and 23 of 30 (76.7%) endometrioid, demonstrated negative or lowerNOTCH2expression than normal fallopian tubal epithelium or ovarian surface epithelium. In contrast, 10 of 15 (66.7%) mucinous carcinomas had a high level ofNOTCH2expression and consistently demonstrated intense polarized staining (P<.001). The apical expression ofNOTCH2protein present in the normal fallopian tube epithelium and many borderline tumors was absent in the high grade carcinomas, most notably in papillary serous.


CONCLUSIONS
DecreasedNOTCH2expression is associated with the poorly differentiated serous epithelial ovarian carcinoma histology. Further studies are needed to assess the functional role ofNOTCH2in ovarian cancer and its effect on prognosis.
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, United States of America.
Vijaya
V
Galic
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, United States of America.
Carrie J
CJ
Shawber
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, United States of America.
Claire
C
Reeves
Department of Obstetrics and Gynecology, University of Alabama, Birmingham Alabama, United States of America.
Monjri
M
Shah
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, United States of America.
Aino
A
Murtomaki
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, United States of America.
Jason
J
Wright
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, United States of America.
Thomas
T
Herzog
Department of Pathology, Columbia University Medical Center, New York, New York, United States of America.
Guo Xia
GX
Tong
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, United States of America.
Jan
J
Kitajewski
NOTCH2; immunohistochemistry; ovarian cancer; tumor suppressor