Loss of DNA mismatch repair protein hMSH6 in ovarian cancer is histotype-specific.
Microsatellite instability (MSI) due to defects in DNA mismatch repair genes may be involved in the development of a subset of human ovarian carcinomas. The role of one such gene, hMSH6, in ovarian cancer is not well documented. We investigated the expression of hMSH6 protein in different histotypes of ovarian carcinoma and the associations between loss of hMSH6 protein and tumor grade, disease stage, familial history of cancer and patient survival. We stained an ovarian carcinoma tissue microarray consisting of formalin-fixed, paraffin-embedded tissue samples from 322 patients with an anti-hMSH6 antibody and scored the results semiquantitatively as negative or positive. Twelve cases were excluded owing to loss of cores during staining. Absence of hMSH6 protein was noted in 20 of 230 serous carcinomas (8.7%), in 7 of 16 clear cell carcinomas (43.7%), in 4 of 34 endometrioid carcinomas (11.7%), in 1 of 14 malignant mixed Müllerian tumors, 2 of 6 mucinous carcinomas, 0 of 2 transitional cell carcinomas and in 0 of 8 undifferentiated carcinomas. Loss of hMSH6 protein was not associated with survival, patient age, tumor grade, or disease stage but was associated with clear cell, mucinous and endometrioid carcinoma histology (P<0.007). These findings indicate that loss of hMSH6 expression in ovarian carcinoma is more common in certain histologic subtypes, particularly in clear cell, endometrioid, and mucinous carcinoma, suggesting that loss of hMSH6 function may participate in the pathogenesis of these subtypes of cancer. Loss of hMSH6 expression did not predict survival and was not associated with disease stage, tumor grade, patient age or family history of cancer.
Zhai
Qihui Jim
QJ
Department of Pathology, The Methodist Hospital, Houston, Texas, USA.
Rosen
Daniel Gustavo
DG
Lu
Karen
K
Liu
Jinsong
J
Nat Genet. 1999 Oct;23(2):142-4
10508506
Oncol Rep. 2004 Dec;12(6):1217-9
15547740
Cancer. 2001 Dec 1;92(11):2829-36
11753956
Cancer Res. 2000 Apr 15;60(8):2225-31
10786688
Jpn J Cancer Res. 1994 Dec;85(12):1247-56
7852189
Int J Gynecol Pathol. 1999 Apr;18(2):158-62
10202674
Pathology. 1979 Jan;11(1):5-26
431978
Science. 1995 Jun 30;268(5219):1915-7
7604266
Br J Cancer. 1998 Oct;78(8):981-5
9792139
Cancer Res. 1999 Oct 15;59(20):5068-74
10537275
Mod Pathol. 2004 Jul;17(7):790-7
15073602
Br J Obstet Gynaecol. 1989 Aug;96(8):889-92
2775686
Cancer Genet Cytogenet. 2000 Feb;117(1):61-5
10700869
Cancer Res. 1998 Nov 15;58(22):5248-57
9823339
Pathology. 1979 Apr;11(2):251-82
460950
Am J Surg Pathol. 2004 Apr;28(4):496-504
15087669
Cancer. 1996 Sep 15;78(6):1149-67
8826936
Cancer Res. 2001 Jun 1;61(11):4371-4
11389062
Histol Histopathol. 1999 Jan;14(1):269-77
9987671
Cancer Res. 2001 Feb 15;61(4):1619-23
11245474
Am J Dermatopathol. 2001 Aug;23(4):308-14
11481522
Int J Cancer. 1995 Dec 20;64(6):361-6
8550235
Br J Cancer. 1995 Aug;72(2):376-82
7640221
Carcinogenesis. 1996 Sep;17(9):1799-804
8824498
Histopathology. 2001 Feb;38(2):87-95
11207821
Natl Cancer Inst Monogr. 1975 Oct;42:5-7
1234636
Am J Hum Genet. 1999 Nov;65(5):1291-8
10521294
Nat Genet. 1997 Nov;17(3):271-2
9354786
Clin Cancer Res. 2002 Jan;8(1):138-43
11801550
Int J Cancer. 2000 Mar 1;85(5):606-13
10699937
Cancer Res. 1997 Sep 15;57(18):3920-3
9307272
Cancer Res. 2002 Aug 15;62(16):4722-9
12183431
Pathology. 1979 Jul;11(3):493-532
230444
Int J Oncol. 2000 Mar;16(3):567-76
10675491
Gynecol Oncol. 2001 Mar;80(3):346-9
11263929
Hum Pathol. 2004 May;35(5):552-9
15138928