TY - JOUR
T1 - Microsatellite instability and alteration of the expression of hMLH1 and hMSH2 in ovarian clear cell carcinoma
AU - Cai, Kathy Qi
AU - Albarracin, Constance
AU - Rosen, Daniel
AU - Zhong, Rocksheng
AU - Zheng, Wenxin
AU - Luthra, Rajyalakshmi
AU - Broaddus, Russell
AU - Liu, Jinsong
N1 - Funding Information:
Supported by a grant from the American Cancer Society (RSG-04-028-CCE, to D.R.), the National Cancer Institute (P01CA64602-1) and institutional start-up funds, an Institutional Research Grant, and a Career Development Award from the M.D. Anderson Cancer Center SPORE on Ovarian Cancer (to J.L.).
PY - 2004/5
Y1 - 2004/5
N2 - Microsatellite instability (MSI) is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is caused by defects in the DNA mismatch repair genes. MSI has also been observed in various sporadic cancers, including colorectal, gastric, and endometrial. The role and incidence of MSI in ovarian clear cell carcinoma remain unknown. This study was conducted to evaluate the frequency of MSI in ovarian clear cell carcinomas and to evaluate the sensitivity and specificity of immunohistochemistry in predicting mismatch-repair gene deficiency. A total of 42 ovarian clear cell carcinomas were analyzed for MSI using a panel of 5 microsatellite markers (BAT25, BAT26, D5S346, D2S123, and D17S250). Alterations in the expression of hMLH1 and hMSH2 proteins in these tumors were examined. Of the 42 ovarian clear cell tumors analyzed, 6 demonstrated a high level of MSI (MSI-H), 3 demonstrated a low level of MSI (MSI-L), and the remaining 33 exhibited microsatellite stability (MSS). No correlation was found between MSI level and patient age or tumor stage or size (P > 0.05). Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 6 (67.7%) MSI-H tumors, whereas 34 of the 36 (94.4%) MSI-L or MSS tumors expressed both the hMLH1 and hMSH2 gene products. Our results indicate that MSI-H is involved in the development of a subset of ovarian clear cell carcinomas. A strong correlation exists between alterations in the expression of hMLH1 and hMSH2 and the presence of MSI-H in these tumors. However, immunohistochemical testing alone may miss a small fraction of cases with MSI-H.
AB - Microsatellite instability (MSI) is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is caused by defects in the DNA mismatch repair genes. MSI has also been observed in various sporadic cancers, including colorectal, gastric, and endometrial. The role and incidence of MSI in ovarian clear cell carcinoma remain unknown. This study was conducted to evaluate the frequency of MSI in ovarian clear cell carcinomas and to evaluate the sensitivity and specificity of immunohistochemistry in predicting mismatch-repair gene deficiency. A total of 42 ovarian clear cell carcinomas were analyzed for MSI using a panel of 5 microsatellite markers (BAT25, BAT26, D5S346, D2S123, and D17S250). Alterations in the expression of hMLH1 and hMSH2 proteins in these tumors were examined. Of the 42 ovarian clear cell tumors analyzed, 6 demonstrated a high level of MSI (MSI-H), 3 demonstrated a low level of MSI (MSI-L), and the remaining 33 exhibited microsatellite stability (MSS). No correlation was found between MSI level and patient age or tumor stage or size (P > 0.05). Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 6 (67.7%) MSI-H tumors, whereas 34 of the 36 (94.4%) MSI-L or MSS tumors expressed both the hMLH1 and hMSH2 gene products. Our results indicate that MSI-H is involved in the development of a subset of ovarian clear cell carcinomas. A strong correlation exists between alterations in the expression of hMLH1 and hMSH2 and the presence of MSI-H in these tumors. However, immunohistochemical testing alone may miss a small fraction of cases with MSI-H.
KW - Immunohistochemistry
KW - Microsatellite instability
KW - Ovarian clear cell carcinoma
KW - hMLH1
KW - hMSH2
UR - http://www.scopus.com/inward/record.url?scp=2442670288&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442670288&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2003.12.009
DO - 10.1016/j.humpath.2003.12.009
M3 - Article
C2 - 15138928
AN - SCOPUS:2442670288
SN - 0046-8177
VL - 35
SP - 552
EP - 559
JO - Human pathology
JF - Human pathology
IS - 5
ER -