Woo Jin Lee1, Ye Jin Lee2, Myoung Eun Choi2, Kyung A Yun2, Chong Hyun Won2, Mi Woo Lee2, Jee Ho Choi2, Sung Eun Chang3. 1. Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: uucm79@hanmail.net. 2. Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 3. Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: csesnumd@gmail.com.
Abstract
BACKGROUND: Lymphocyte-activating gene 3 (LAG-3) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (TIGIT) domains are emerging checkpoint proteins. OBJECTIVE: We evaluated LAG-3 and TIGIT protein expression patterns, correlated these patterns with programmed cell death 1 (PD-1) protein expression, and determined their effects on clinicopathologic characteristics and biologic responses in melanoma. METHODS: Diagnostic tissue from 124 patients with melanoma were evaluated for LAG-3, TIGIT, and PD-1 expression by immunohistochemistry. Clinicopathologic features and survival were analyzed according to the expression of LAG-3, TIGIT, and PD-1. RESULTS: LAG-3 and TIGIT expression on tumor-infiltrating lymphocytes were significantly correlated with that of PD-1 and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of disease. However, PD-1 expression was not associated with clinicopathologic variables of prognostic significance. High expression of either LAG-3 or TIGIT was associated with worse survival. Subgroup analysis on the basis of Breslow thickness showed that both LAG-3 and TIGIT have prognostic significance regardless of tumor thickness. High expression of PD-1 was not predictive of survival. LIMITATIONS: Retrospective study in a single institution and possibility of type 1 error. CONCLUSION: Expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma.
BACKGROUND:Lymphocyte-activating gene 3 (LAG-3) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (TIGIT) domains are emerging checkpoint proteins. OBJECTIVE: We evaluated LAG-3 and TIGIT protein expression patterns, correlated these patterns with programmed cell death 1 (PD-1) protein expression, and determined their effects on clinicopathologic characteristics and biologic responses in melanoma. METHODS: Diagnostic tissue from 124 patients with melanoma were evaluated for LAG-3, TIGIT, and PD-1 expression by immunohistochemistry. Clinicopathologic features and survival were analyzed according to the expression of LAG-3, TIGIT, and PD-1. RESULTS:LAG-3 and TIGIT expression on tumor-infiltrating lymphocytes were significantly correlated with that of PD-1 and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of disease. However, PD-1 expression was not associated with clinicopathologic variables of prognostic significance. High expression of either LAG-3 or TIGIT was associated with worse survival. Subgroup analysis on the basis of Breslow thickness showed that both LAG-3 and TIGIT have prognostic significance regardless of tumor thickness. High expression of PD-1 was not predictive of survival. LIMITATIONS: Retrospective study in a single institution and possibility of type 1 error. CONCLUSION: Expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma.
Authors: Vera Petrova; Ihor Arkhypov; Rebekka Weber; Christopher Groth; Peter Altevogt; Jochen Utikal; Viktor Umansky Journal: Int J Mol Sci Date: 2020-03-30 Impact factor: 5.923
Authors: Katrin Pansy; Barbara Uhl; Jelena Krstic; Marta Szmyra; Karoline Fechter; Ana Santiso; Lea Thüminger; Hildegard Greinix; Julia Kargl; Katharina Prochazka; Julia Feichtinger; Alexander Ja Deutsch Journal: Int J Mol Sci Date: 2021-12-10 Impact factor: 5.923