Intratumoral CD8+ T Lymphocytes as a Prognostic Factor of Survival in Endometrial Carcinoma

• Published in: Clinical cancer research Vol. 10; no. 13; pp. 4450 - 4456
• Main Authors: Kondratiev, Svetlana, Sabo, Edmond, Yakirevich, Evgeny, Lavie, Ofer, Resnick, Murray B.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2004
• Subjects: Antineoplastic agents; Biological and medical sciences; Carcinoma, Endometrioid - blood; Carcinoma, Endometrioid - diagnosis; Carcinoma, Endometrioid - mortality; Carcinoma, Papillary - blood; Carcinoma, Papillary - diagnosis; Carcinoma, Papillary - mortality; CD8 Antigens - biosynthesis; CD8-Positive T-Lymphocytes - metabolism; Cell Survival; Cytoplasm - metabolism; Endometrial Neoplasms - blood; Endometrial Neoplasms - diagnosis; Endometrial Neoplasms - mortality; Female; Granzymes; Humans; Immunohistochemistry; Medical sciences; Multivariate Analysis; Pharmacology. Drug treatments; Prognosis; Risk Factors; Serine Endopeptidases - biosynthesis; T-Lymphocytes - metabolism; Time Factors; Treatment Outcome; Tumors; Prognosis; Survival; Endometrial carcinoma; T-Lymphocyte; Female genital diseases
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-0732-3

Purpose: CTLs are a prominent immune component infiltrating many solid tumors. These cells are considered to be a manifestation of host-immune response to the tumor; however, their prognostic significance remains a subject of considerable debate. The objective of this study was to evaluate the distribution pattern and prognostic value of CD8 + T cells in endometrial carcinoma. Experimental Design: We studied 90 cases of endometrial carcinoma, including 75 endometrioid and 15 papillary serous carcinomas. Immunohistochemical staining for CD8 and granzyme B was performed on paraffin-embedded sections. The number of immunohistochemically staining CD8 + T cells was enumerated in the following four regions: lymphocytes infiltrating the tumor epithelium at the invasive border, within the underlying tumor stroma, within the superficial tumor epithelium, and in the perivascular areas of the myometrium. Results: Patients with >10 CD8 + T lymphocytes/high-power field within the tumor epithelium at the invasive border displayed improved overall survival compared with patients with fewer intraepithelial CD8 + T lymphocytes (87 and 50%, respectively; P = 0.027). Multivariate analysis revealed that stage, vascular invasion, grade, and the number of intraepithelial CD8 + T lymphocytes at the invasive border were the only independent predictors of survival ( P < 0.0001, P = 0.001, P = 0.011, and P = 0.025, respectively). Granzyme B + cytoplasmatic granules were detected in a high proportion of CTLs, confirming their activated cytotoxic phenotype. Conclusions: Our study demonstrates for the first time that increased numbers of CTLs at the invasive border may be a reliable independent prognostic factor of survival in patients with endometrial carcinoma.