Tumor-Infiltrating Lymphocyte Grade Is an Independent Predictor of Sentinel Lymph Node Status and Survival in Patients With Cutaneous Melanoma

被引:666
作者
Azimi, Farhad [1 ]
Scolyer, Richard A. [1 ,2 ,4 ]
Rumcheva, Pavlina [3 ]
Moncrieff, Marc [1 ,2 ]
Murali, Rajmohan [1 ,2 ,4 ]
McCarthy, Stanley W. [1 ,2 ,4 ]
Saw, Robyn P. [1 ,2 ,4 ]
Thompson, John F. [1 ,2 ,4 ]
机构
[1] Melanoma Inst Australia, Sydney, NSW 2060, Australia
[2] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia
[3] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia
[4] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia
基金
英国医学研究理事会;
关键词
AMERICAN JOINT COMMITTEE; CLINICAL STAGE-I; PROGNOSTIC-SIGNIFICANCE; MALIGNANT-MELANOMA; MITOTIC RATE; METASTATIC MELANOMA; BIOPSY; MODEL; INTERLEUKIN-2; IMMUNOTHERAPY;
D O I
10.1200/JCO.2011.37.8539
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose To determine whether density and distribution of tumor-infiltrating lymphocytes (TILs; TIL grade) is an independent predictor of sentinel lymph node (SLN) status and survival in patients with clinically localized primary cutaneous melanoma. Methods From the Melanoma Institute Australia database, 1,865 patients with a single primary melanoma >= 0.75 mm in thickness were identified. The associations of clinical and pathologic factors with SLN status, recurrence-free survival (RFS), and melanoma-specific survival (MSS) were analyzed. Results The majority of patients had either no (TIL grade 0; 35.4%) or few (TIL grade 1; 45.1%) TILs, with a minority showing moderate (TIL grade 2; 16.3%) or marked (TIL grade 3; 3.2%) TILs. Tumor thickness, mitotic rate, and Clark level were inversely correlated with TIL grade (each P < .001). SLN biopsy was performed in 1,138 patients (61.0%) and was positive in 252 (22.1%). There was a significant inverse association between SLN status and TIL grade (SLN positivity rates for each TIL grade: 0, 27.8%; 1, 20.1%; 2, 18.3%; 3, 5.6%; P < .001). Predictors of SLN positivity were decreasing age (P < .001), decreasing TIL grade (P < .001), ulceration (P = .003), increasing tumor thickness (P = .01), satellitosis (P = .03), and increasing mitoses (P = .03). The 5-year MSS and RFS rates were 83% and 76%, respectively (median follow-up, 43 months). Tumor thickness (P < .001), ulceration (P < .001), satellitosis (P < .001), mitotic rate (P = .003), TIL grade (P < .001), and sex (P = .01) were independent predictors of MSS. Patients with TIL grade 3 tumors had 100% survival. Conclusion TIL grade is an independent predictor of survival and SLN status in patients with melanoma. Patients with a pronounced TIL infiltrate have an excellent prognosis.
引用
收藏
页码:2678 / 2683
页数:6
相关论文
共 52 条
[1]   Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma - An analysis of 3661 patients from a single center [J].
Azzola, MF ;
Shaw, HM ;
Thompson, JF ;
Soong, SJ ;
Scolyer, RA ;
Watson, GF ;
Colman, MH ;
Zhang, YT .
CANCER, 2003, 97 (06) :1488-1498
[2]   Final Version of 2009 AJCC Melanoma Staging and Classification [J].
Balch, Charles M. ;
Gershenwald, Jeffrey E. ;
Soong, Seng-jaw ;
Thompson, John F. ;
Atkins, Michael B. ;
Byrd, David R. ;
Buzaid, Antonio C. ;
Cochran, Alistair J. ;
Coit, Daniel G. ;
Ding, Shouluan ;
Eggermont, Alexander M. ;
Flaherty, Keith T. ;
Gimotty, Phyllis A. ;
Kirkwood, John M. ;
McMasters, Kelly M. ;
Mihm, Martin C., Jr. ;
Morton, Donald L. ;
Ross, Merrick I. ;
Sober, Arthur J. ;
Sondak, Vernon K. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6199-6206
[3]   Prognostic factors analysis of 17,600 melanoma patients: Validation of the American Joint Committee on Cancer melanoma staging system [J].
Balch, CM ;
Soong, SJ ;
Gershenwald, JE ;
Thompson, JF ;
Reintgen, DS ;
Cascinelli, N ;
Urist, M ;
McMasters, KM ;
Ross, MI ;
Kirkwood, JM ;
Atkins, MB ;
Thompson, JA ;
Coit, DG ;
Byrd, D ;
Desmond, R ;
Zhang, YT ;
Liu, PY ;
Lyman, GH ;
Morabito, A .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (16) :3622-3634
[4]   Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma [J].
Balch, CM ;
Buzaid, AC ;
Soong, SJ ;
Atkins, MB ;
Cascinelli, N ;
Coit, DG ;
Fleming, ID ;
Gershenwald, JE ;
Houghton, A ;
Kirkwood, JM ;
McMasters, KM ;
Mihm, MF ;
Morton, DL ;
Reintgen, DS ;
Ross, MI ;
Sober, A ;
Thompson, JA ;
Thompson, JF .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (16) :3635-3648
[5]  
Barnhill RL, 1996, CANCER-AM CANCER SOC, V78, P427
[6]   Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival [J].
Bogunovic, Dusan ;
O'Neill, David W. ;
Belitskaya-Levy, Ilana ;
Vacic, Vladimir ;
Yu, Yi-Lo ;
Adams, Sylvia ;
Darvishian, Farbod ;
Berman, Russell ;
Shapiro, Richard ;
Pavlick, Anna C. ;
Lonardi, Stefano ;
Zavadil, Jiri ;
Osman, Iman ;
Bhardwaj, Nina .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (48) :20429-20434
[7]   Human T cell responses against melanoma [J].
Boon, Thierry ;
Coulie, Pierre G. ;
Van den Eynde, Benoit J. ;
van der Bruggen, Pierre .
ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :175-208
[8]  
Burton AL, 2011, AM SURGEON, V77, P188
[9]   Progressive Upregulation of PD-1 in Primary and Metastatic Melanomas Associated with Blunted TCR Signaling in Infiltrating T Lymphocytes [J].
Chapon, Maxime ;
Randriamampita, Clotilde ;
Maubec, Eve ;
Badoual, Cecile ;
Fouquet, Stephane ;
Wang, Shu-Fang ;
Marinho, Eduardo ;
Farhi, David ;
Garcette, Marylene ;
Jacobelli, Simon ;
Rouquette, Alexandre ;
Carlotti, Agnes ;
Girod, Angelique ;
Prevost-Blondel, Armelle ;
Trautmann, Alain ;
Avril, Marie-Francoise ;
Bercovici, Nadege .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2011, 131 (06) :1300-1307
[10]   MODEL PREDICTING SURVIVAL IN STAGE-I MELANOMA BASED ON TUMOR PROGRESSION [J].
CLARK, WH ;
ELDER, DE ;
GUERRY, D ;
BRAITMAN, LE ;
TROCK, BJ ;
SCHULTZ, D ;
SYNNESTVEDT, M ;
HALPERN, AC .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1989, 81 (24) :1893-1904