Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial carcinoma.
OBJECTIVE
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.


METHODS
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.
Kondratiev
Svetlana
S
Department of Pathology and Division of Gynecologic Oncology, Carmel Medical Center and the Technion Rappoport Faculty of Medicine, Haifa, Israel.
Sabo
Edmond
E
Yakirevich
Evgeny
E
Lavie
Ofer
O
Resnick
Murray B
MB
D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D002291:Carcinoma, Papillary / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D016827:CD8 Antigens; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases