Intratumoral CD8+ lymphocyte infiltration as a prognostic factor and its relationship with cyclooxygenase 2 expression and microsatellite instability in endometrial cancer

Tomohiro Suemori, Nobuyuki Susumu, Takashi Iwata, Kouji Banno, Wataru Yamagami, Akira Hirasawa, Kokichi Sugano, Eri Matsumoto, Daisuke Aoki

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective Microsatellite instability (MSI) is caused by a defective DNA mismatch repair system. Colorectal cancer in MSI-positive patients is characterized by an increased number of tumor-infiltrating lymphocytes. On the other hand, it has recently been reported that cyclooxygenase 2 (COX-2) suppresses antitumor immunity. The objectives of the present study were to clarify the relationships among MSI status, COX-2 expression, and antitumor immune status and to verify impact of these factors on the prognosis of endometrial cancer. Methods The data of 123 patients with endometrial cancer were analyzed. The numbers of tumor-infiltrating CD8+ T lymphocytes within cancer cell nests (TILs), as a representative of the antitumor immunity, and COX-2 expression levels in the tumor cells were analyzed by immunohistochemical staining. Microsatellite instability was evaluated by polymerase chain reaction analysis for 11 markers. Fisher exact probability test, Kaplan-Meier method, and proportional hazards analysis were used for the statistical analyses. Results The MSI-positive tumors showed significantly higher grades (G2 or G3) and significantly larger numbers of TILs than did the MSI-negative tumors. The COX-2-high group showed significantly fewer TILs than did the COX-2-low group. Multivariate analysis identified a low number of TILs (<10), positive lymph node involvement, and high tumor malignancy grade as factors independently associated with poor prognosis. The prognosis was significantly poorer in the patients with MSI-positive tumors with high COX-2 expression than in those with MSI-positive tumors showing low COX-2 expression. Conclusions The number of TILs, which was increased by MSI and decreased by COX-2 expression, was associated with a poorer prognosis in patients with endometrial cancer. We also propose that COX-2 may block MSI-activated TILs in the tumor microenvironment.

Original languageEnglish
Pages (from-to)1165-1172
Number of pages8
JournalInternational Journal of Gynecological Cancer
Volume25
Issue number7
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Fingerprint

Microsatellite Instability
Cyclooxygenase 2
Endometrial Neoplasms
Lymphocytes
Neoplasms
Immunity
Tumor-Infiltrating Lymphocytes
DNA Mismatch Repair
Tumor Microenvironment
Kaplan-Meier Estimate
Colorectal Neoplasms
Multivariate Analysis
Lymph Nodes
Staining and Labeling
T-Lymphocytes
Polymerase Chain Reaction

Keywords

  • CD8<sup>+</sup> T lymphocytes
  • Cyclooxygenase 2
  • Endometrial cancer
  • Microsatellite instability

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Cite this

Intratumoral CD8+ lymphocyte infiltration as a prognostic factor and its relationship with cyclooxygenase 2 expression and microsatellite instability in endometrial cancer. / Suemori, Tomohiro; Susumu, Nobuyuki; Iwata, Takashi; Banno, Kouji; Yamagami, Wataru; Hirasawa, Akira; Sugano, Kokichi; Matsumoto, Eri; Aoki, Daisuke.

In: International Journal of Gynecological Cancer, Vol. 25, No. 7, 01.01.2015, p. 1165-1172.

Research output: Contribution to journalArticle

Suemori, Tomohiro ; Susumu, Nobuyuki ; Iwata, Takashi ; Banno, Kouji ; Yamagami, Wataru ; Hirasawa, Akira ; Sugano, Kokichi ; Matsumoto, Eri ; Aoki, Daisuke. / Intratumoral CD8+ lymphocyte infiltration as a prognostic factor and its relationship with cyclooxygenase 2 expression and microsatellite instability in endometrial cancer. In: International Journal of Gynecological Cancer. 2015 ; Vol. 25, No. 7. pp. 1165-1172.
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abstract = "Objective Microsatellite instability (MSI) is caused by a defective DNA mismatch repair system. Colorectal cancer in MSI-positive patients is characterized by an increased number of tumor-infiltrating lymphocytes. On the other hand, it has recently been reported that cyclooxygenase 2 (COX-2) suppresses antitumor immunity. The objectives of the present study were to clarify the relationships among MSI status, COX-2 expression, and antitumor immune status and to verify impact of these factors on the prognosis of endometrial cancer. Methods The data of 123 patients with endometrial cancer were analyzed. The numbers of tumor-infiltrating CD8+ T lymphocytes within cancer cell nests (TILs), as a representative of the antitumor immunity, and COX-2 expression levels in the tumor cells were analyzed by immunohistochemical staining. Microsatellite instability was evaluated by polymerase chain reaction analysis for 11 markers. Fisher exact probability test, Kaplan-Meier method, and proportional hazards analysis were used for the statistical analyses. Results The MSI-positive tumors showed significantly higher grades (G2 or G3) and significantly larger numbers of TILs than did the MSI-negative tumors. The COX-2-high group showed significantly fewer TILs than did the COX-2-low group. Multivariate analysis identified a low number of TILs (<10), positive lymph node involvement, and high tumor malignancy grade as factors independently associated with poor prognosis. The prognosis was significantly poorer in the patients with MSI-positive tumors with high COX-2 expression than in those with MSI-positive tumors showing low COX-2 expression. Conclusions The number of TILs, which was increased by MSI and decreased by COX-2 expression, was associated with a poorer prognosis in patients with endometrial cancer. We also propose that COX-2 may block MSI-activated TILs in the tumor microenvironment.",
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T1 - Intratumoral CD8+ lymphocyte infiltration as a prognostic factor and its relationship with cyclooxygenase 2 expression and microsatellite instability in endometrial cancer

AU - Suemori, Tomohiro

AU - Susumu, Nobuyuki

AU - Iwata, Takashi

AU - Banno, Kouji

AU - Yamagami, Wataru

AU - Hirasawa, Akira

AU - Sugano, Kokichi

AU - Matsumoto, Eri

AU - Aoki, Daisuke

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N2 - Objective Microsatellite instability (MSI) is caused by a defective DNA mismatch repair system. Colorectal cancer in MSI-positive patients is characterized by an increased number of tumor-infiltrating lymphocytes. On the other hand, it has recently been reported that cyclooxygenase 2 (COX-2) suppresses antitumor immunity. The objectives of the present study were to clarify the relationships among MSI status, COX-2 expression, and antitumor immune status and to verify impact of these factors on the prognosis of endometrial cancer. Methods The data of 123 patients with endometrial cancer were analyzed. The numbers of tumor-infiltrating CD8+ T lymphocytes within cancer cell nests (TILs), as a representative of the antitumor immunity, and COX-2 expression levels in the tumor cells were analyzed by immunohistochemical staining. Microsatellite instability was evaluated by polymerase chain reaction analysis for 11 markers. Fisher exact probability test, Kaplan-Meier method, and proportional hazards analysis were used for the statistical analyses. Results The MSI-positive tumors showed significantly higher grades (G2 or G3) and significantly larger numbers of TILs than did the MSI-negative tumors. The COX-2-high group showed significantly fewer TILs than did the COX-2-low group. Multivariate analysis identified a low number of TILs (<10), positive lymph node involvement, and high tumor malignancy grade as factors independently associated with poor prognosis. The prognosis was significantly poorer in the patients with MSI-positive tumors with high COX-2 expression than in those with MSI-positive tumors showing low COX-2 expression. Conclusions The number of TILs, which was increased by MSI and decreased by COX-2 expression, was associated with a poorer prognosis in patients with endometrial cancer. We also propose that COX-2 may block MSI-activated TILs in the tumor microenvironment.

AB - Objective Microsatellite instability (MSI) is caused by a defective DNA mismatch repair system. Colorectal cancer in MSI-positive patients is characterized by an increased number of tumor-infiltrating lymphocytes. On the other hand, it has recently been reported that cyclooxygenase 2 (COX-2) suppresses antitumor immunity. The objectives of the present study were to clarify the relationships among MSI status, COX-2 expression, and antitumor immune status and to verify impact of these factors on the prognosis of endometrial cancer. Methods The data of 123 patients with endometrial cancer were analyzed. The numbers of tumor-infiltrating CD8+ T lymphocytes within cancer cell nests (TILs), as a representative of the antitumor immunity, and COX-2 expression levels in the tumor cells were analyzed by immunohistochemical staining. Microsatellite instability was evaluated by polymerase chain reaction analysis for 11 markers. Fisher exact probability test, Kaplan-Meier method, and proportional hazards analysis were used for the statistical analyses. Results The MSI-positive tumors showed significantly higher grades (G2 or G3) and significantly larger numbers of TILs than did the MSI-negative tumors. The COX-2-high group showed significantly fewer TILs than did the COX-2-low group. Multivariate analysis identified a low number of TILs (<10), positive lymph node involvement, and high tumor malignancy grade as factors independently associated with poor prognosis. The prognosis was significantly poorer in the patients with MSI-positive tumors with high COX-2 expression than in those with MSI-positive tumors showing low COX-2 expression. Conclusions The number of TILs, which was increased by MSI and decreased by COX-2 expression, was associated with a poorer prognosis in patients with endometrial cancer. We also propose that COX-2 may block MSI-activated TILs in the tumor microenvironment.

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