Journal of Nippon Medical School: Vol.70 No.1 page.040

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ArticleTitle Association of Ovarian Tumor Epithelium Coexpressing HLA-DR and CA-125 Antigens with Tumor Infiltrating Cytotoxic T Lymphocytes

AuthorList Norihiro Matsushita¹, Mohammad Ghazizadeh², Hideki Konishi¹, Tsutomu Araki¹

Affiliation ¹Department of Obstetrics and Gynecology, Nippon Medical School ²Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School

Language EN

Volume 70

Issue 1

Year 2003

Page 40-44

Received September 11, 2002

Accepted October 7, 2002

Keywords ovarian tumor, antigens, HLA-DR, CA-125, tumor infiltrating cytotoxic T lymphocytes, TILs, CD 8

Abstract
Understanding of the relationship between tumor infiltrating cytotoxic T lymphocytes (CD 8⁺TILs) and tumor cells as well as tumor-associated antigens is important and may reflect the extent of immune response of the patient to the tumor, thus providing a useful clue relevant to the prognosis. The purpose of this study was to determine the relationship between the expression of HLA-DR and CA-125 antigens and the presence of CD 8⁺TILs with regard to the established clinicopathological factors of ovarian carcinomas using immunohistochemical methods. Thirty-one ovarian carcinomas consisting of 20 serous, 7 mucinous, and 4 clear cell types were examined. Of these, 18 (58%) and 22 (71%) were positive for HLA-DR and CA-125 antigens respectively, and the overall mean number of the CD 8⁺TILs was 7.2±2.9. A significant association was observed between the mean number of CD8⁺TILs and tumor grade (P=0.01), disease stage (P=0.003), and patient outcome (P=0.01). The mean number of CD 8⁺TILs in HLA-DR positive (8.6±2.2) or CA-125 positive (8.4±2.1) tumors was significantly higher than that in HLA-DR negative (5.2±2.5; P=0.0003) or CA-125 negative (4.2±2.2; P=0.00002) tumors. These signifcant levels were further enhanced by one order of magnitude when the mean number of CD 8⁺TILs in tumors postive for both HLA-DR and CA-125 antigens (9.1±1.7) was compared to that in HLA-DR negative or CA-125 negative tumors. The frequency of cancer-related deaths in HLA-DR and CA-125 positive tumors was significantly lower than in the negative tumors (P=0.01). These data suggest that concurrent expression of HLA-DR and CA-125 antigens may augment the immune response of the patient to the tumor, thus providing a potential clue relevant to the prognosis.

Correspondence to Mohammad Ghazizadeh, MD, Department of Molecular Pathology, Insutitute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan
ciem@nms.ac.jp

ArticleTitle	Association of Ovarian Tumor Epithelium Coexpressing HLA-DR and CA-125 Antigens with Tumor Infiltrating Cytotoxic T Lymphocytes
AuthorList	Norihiro Matsushita¹, Mohammad Ghazizadeh², Hideki Konishi¹, Tsutomu Araki¹
Affiliation	¹Department of Obstetrics and Gynecology, Nippon Medical School ²Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School
Language	EN
Volume	70
Issue	1
Year	2003
Page	40-44
Received	September 11, 2002
Accepted	October 7, 2002
Keywords	ovarian tumor, antigens, HLA-DR, CA-125, tumor infiltrating cytotoxic T lymphocytes, TILs, CD 8
Abstract	Understanding of the relationship between tumor infiltrating cytotoxic T lymphocytes (CD 8⁺TILs) and tumor cells as well as tumor-associated antigens is important and may reflect the extent of immune response of the patient to the tumor, thus providing a useful clue relevant to the prognosis. The purpose of this study was to determine the relationship between the expression of HLA-DR and CA-125 antigens and the presence of CD 8⁺TILs with regard to the established clinicopathological factors of ovarian carcinomas using immunohistochemical methods. Thirty-one ovarian carcinomas consisting of 20 serous, 7 mucinous, and 4 clear cell types were examined. Of these, 18 (58%) and 22 (71%) were positive for HLA-DR and CA-125 antigens respectively, and the overall mean number of the CD 8⁺TILs was 7.2±2.9. A significant association was observed between the mean number of CD8⁺TILs and tumor grade (P=0.01), disease stage (P=0.003), and patient outcome (P=0.01). The mean number of CD 8⁺TILs in HLA-DR positive (8.6±2.2) or CA-125 positive (8.4±2.1) tumors was significantly higher than that in HLA-DR negative (5.2±2.5; P=0.0003) or CA-125 negative (4.2±2.2; P=0.00002) tumors. These signifcant levels were further enhanced by one order of magnitude when the mean number of CD 8⁺TILs in tumors postive for both HLA-DR and CA-125 antigens (9.1±1.7) was compared to that in HLA-DR negative or CA-125 negative tumors. The frequency of cancer-related deaths in HLA-DR and CA-125 positive tumors was significantly lower than in the negative tumors (P=0.01). These data suggest that concurrent expression of HLA-DR and CA-125 antigens may augment the immune response of the patient to the tumor, thus providing a potential clue relevant to the prognosis.
Correspondence to	Mohammad Ghazizadeh, MD, Department of Molecular Pathology, Insutitute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan ciem@nms.ac.jp