Nodular primary cutaneous melanoma is associated with PD-L1 expression

被引:10
作者
Giavina-Bianchi, Mara [1 ,2 ]
Giavina-Bianchi, Pedro [2 ]
Sotto, Mirian Nacagamo [1 ]
Rodig, Scott [3 ]
Mihm, Martin, Jr. [4 ]
Festa Neto, Cyro [1 ]
Duncan, Lyn M. [5 ]
Kalil, Jorge [2 ]
机构
[1] Univ Sao Paulo, Dept Dermatol, Fac Med, Av Dr Eneas de Carvalho Aguiar 255,3 Andar, BR-05403900 Sao Paulo, SP, Brazil
[2] Univ Sao Paulo, Div Clin Immunol & Allergy, Fac Med, Av Dr Eneas de Carvalho Aguiar 255,8 Andar, BR-05403900 Sao Paulo, SP, Brazil
[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, 15 Shattuck St, Boston, MA 02115 USA
[4] Emmanuel Coll, Mihm Cutaneous Pathol Consultat Serv, 41 Louis Pasteur St,Room 360, Boston, MA 02115 USA
[5] Harvard Med Sch, Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Warren Bldg 825,55 Fruit St, Boston, MA 02114 USA
基金
巴西圣保罗研究基金会;
关键词
nodular melanoma; PD-L1; PD-1; CD3; CD8; FoxP3; tumor infiltrating lymphocytes; Breslow index; tumor microenvironment; TUMOR-INFILTRATING LYMPHOCYTES; STAGE-III; SURVIVAL; VICTORIA; BLOCKADE; CANCER; PHASE; GRADE;
D O I
10.1684/ejd.2020.3846
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background In previous studies, patients with Stage III melanomas expressing PD-L1 in more than 5% of their neoplastic cells had improved recurrence-free survival with anti-PD1 adjuvant therapy. Objectives We examined PD-L1 expression as a possible biomarker of primary cutaneous melanomas in the vertical growth phase. Materials and Methods This was a retrospective study including 66 patients with invasive primary cutaneous melanomas. We assessed patient clinical and histopathological data and performed immunohistochemical assays with melanoma specimens from the patients to evaluate PD-L1, PD-1, CD3, CD8 and FoxP3 expression. Results We observed PD-L1 expression in 21% (14/66) of our samples, and this expression correlated with increased melanoma thickness (p = 0.002) and nodular-type melanoma (p = 0.001). After adjusting for tumor thickness using a logistic regression test, the association of PD-L1 with nodular-type melanoma persisted. Nodular-type melanoma was 6.48 times more likely to be positive for PD-L1 than other histological types (p = 0.014; 95% CI: 1.46-28.82). As expected, PD-L1 expression correlated with the number of PD-1-expressing cells in the tumor-infiltrating lymphocyte population (p = 0.04). No correlation with PD-L1 was observed for age, sex, tumor site, skin phototype, ulceration status, sentinel lymph node status, metastasis development or survival. Regarding the immune profile of the tumor-infiltrating lymphocytes of PD-L1-positive and -negative groups, no significant differences were observed in the numbers of CD3 +, CD8 + FoxP3-, CD8-FoxP3+ and CD8 + FoxP3+ cells by immunohistochemistry. Conclusion Nodular-type melanoma is associated with PD-L1 expression and may be a suitable candidate for adjuvant therapy of primary melanomas treated with immunotherapy.
引用
收藏
页码:352 / 357
页数:6
相关论文
共 25 条
[1]   Tumor-Infiltrating Lymphocyte Grade Is an Independent Predictor of Sentinel Lymph Node Status and Survival in Patients With Cutaneous Melanoma [J].
Azimi, Farhad ;
Scolyer, Richard A. ;
Rumcheva, Pavlina ;
Moncrieff, Marc ;
Murali, Rajmohan ;
McCarthy, Stanley W. ;
Saw, Robyn P. ;
Thompson, John F. .
JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (21) :2678-2683
[2]   Nodular type and older age as the most significant associations of thick melanoma in Victoria, Australia [J].
Chamberlain, AJ ;
Fritschi, L ;
Giles, GG ;
Dowling, JP ;
Kelly, JW .
ARCHIVES OF DERMATOLOGY, 2002, 138 (05) :609-614
[3]   Prognostic rote of tumoral PDL1 expression and peritumoral FoxP3+lymphocytes in vulvar melanomas [J].
Chlopik, Agata ;
Selim, M. Angelica ;
Peng, Yan ;
Wu, Cheng-Lin ;
Tell-Marti, Gemma ;
Paral, Kristen M. ;
Shalin, Sara C. ;
Kraft, Stefan ;
Hsu, Chao-Kai ;
Shea, Christopher R. ;
Puig, Susana ;
Fernandez-Figueras, Maria-Teresa ;
Biernat, Wojciech ;
Rys, Janusz ;
Marszalek, Andrzej ;
Hoang, Mai P. .
HUMAN PATHOLOGY, 2018, 73 :176-183
[4]   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
[5]  
Clemente CG, 1996, CANCER, V77, P1303, DOI 10.1002/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO
[6]  
2-5
[7]   Increased mast cell density in invasive melanoma [J].
Duncan, LM ;
Richards, LA ;
Mihm, MC .
JOURNAL OF CUTANEOUS PATHOLOGY, 1998, 25 (01) :11-15
[8]   Prognostic and predictive value of AJCC-8 staging in the phase III EORTC1325/KEYNOTE-054 trial of pembrolizumab vs placebo in resected high-risk stage III melanoma [J].
Eggermont, Alexander M. M. ;
Blank, Christian U. ;
Mandala, Mario ;
Long, Georgina, V ;
Atkinson, Victoria G. ;
Dalle, Stephane ;
Haydon, Andrew ;
Lichinitser, Mikhail ;
Khattak, Adnan ;
Carlino, Matteo S. ;
Sandhu, Shahneen ;
Larkin, James ;
Puig, Susana ;
Ascierto, Paolo A. ;
Rutkowski, Piotr ;
Schadendorf, Dirk ;
Koornstra, Rutger ;
Hernandez-Aya, Leonel ;
Di Giacomo, Anna Maria ;
van den Eertwegh, Alfonsus J. M. ;
Grob, Jean-Jacques ;
Gutzmer, Ralf ;
Jamal, Rahima ;
Lorigan, Paul C. ;
Lupinacci, Robert ;
Krepler, Clemens ;
Ibrahim, Nageatte ;
Kicinski, Michal ;
Marreaud, Sandrine ;
van Akkooi, Alexander C. ;
Suciu, Stefan ;
Robert, Caroline .
EUROPEAN JOURNAL OF CANCER, 2019, 116 :148-157
[9]   High response rate to PD-1 blockade in desmoplastic melanomas [J].
Eroglu, Zeynep ;
Zaretsky, Jesse M. ;
Hu-Lieskovan, Siwen ;
Kim, Dae Won ;
Algazi, Alain ;
Johnson, Douglas B. ;
Liniker, Elizabeth ;
Kong, Ben ;
Munhoz, Rodrigo ;
Rapisuwon, Suthee ;
Gherardini, Pier Federico ;
Chmielowski, Bartosz ;
Wang, Xiaoyan ;
Shintaku, I. Peter ;
Wei, Cody ;
Sosman, Jeffrey A. ;
Joseph, Richard W. ;
Postow, Michael A. ;
Carlino, Matteo S. ;
Hwu, Wen-Jen ;
Scolyer, Richard A. ;
Messina, Jane ;
Cochran, Alistair J. ;
Long, Georgina V. ;
Ribas, Antoni .
NATURE, 2018, 553 (7688) :347-+
[10]   Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+T Cells in Cutaneous Melanoma [J].
Giavina-Bianchi, Mara ;
Giavina-Bianchi, Pedro ;
Sotto, Mirian Nacagami ;
Muzikansky, Alona ;
Kalil, Jorge ;
Festa-Neto, Cyro ;
Duncan, Lyn M. .
JOURNAL OF IMMUNOLOGY RESEARCH, 2015, 2015