C A Castaneda1,2, M Castillo3, C Torres-Cabala4, L A Bernabe3, S Casavilca5, V Villegas3, J Sanchez3, M de la Cruz6, J Dunstan6, J M Cotrina6, H L Gomez7, C Chavez3, M P Landa-Baella3, K Tello3, B F Felix3, J Abugattas6. 1. Medical Oncology Department and Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520 Surquillo, 15038, Lima, Peru. carloscastanedaaltamirano@yahoo.com. 2. Faculty of Medicine, Universidad Privada San Juan Bautista, 15067, Lima, Peru. carloscastanedaaltamirano@yahoo.com. 3. Medical Oncology Department and Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520 Surquillo, 15038, Lima, Peru. 4. Departments of Pathology and Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. 5. Pathology Department, Instituto Nacional de Enfermedades Neoplasicas., Av. Angamos Este 2520 Surquillo, 15038, Lima, Peru. 6. Breast Cancer Surgery Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520 Surquillo, 15038, Lima, Peru. 7. Medical Oncology Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520 Surquillo, 15038, Lima, Peru.
Abstract
PURPOSE: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. MATERIALS AND METHODS: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. RESULTS: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. CONCLUSIONS: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .
PURPOSE: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. MATERIALS AND METHODS: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. RESULTS: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. CONCLUSIONS: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .
Authors: Sytse J Piersma; Ekaterina S Jordanova; Mariëtte I E van Poelgeest; Kitty M C Kwappenberg; Jeanette M van der Hulst; Jan W Drijfhout; Cornelis J M Melief; Gemma G Kenter; Gert Jan Fleuren; Rienk Offringa; Sjoerd H van der Burg Journal: Cancer Res Date: 2007-01-01 Impact factor: 12.701
Authors: Daniela Mihic-Probst; Christian D Mnich; Patrick A Oberholzer; Burkhardt Seifert; Bernd Sasse; Holger Moch; Reinhard Dummer Journal: Int J Cancer Date: 2006-05-01 Impact factor: 7.396
Authors: C Romagosa; S Simonetti; L López-Vicente; A Mazo; M E Lleonart; J Castellvi; S Ramon y Cajal Journal: Oncogene Date: 2011-02-07 Impact factor: 9.867
Authors: Franca Piras; Romano Colombari; Luigi Minerba; Daniela Murtas; Carlo Floris; Cristina Maxia; Arianna Corbu; M Teresa Perra; Paola Sirigu Journal: Cancer Date: 2005-09-15 Impact factor: 6.860
Authors: Brian D Robinson; Gabriel L Sica; Yi-Fang Liu; Thomas E Rohan; Frank B Gertler; John S Condeelis; Joan G Jones Journal: Clin Cancer Res Date: 2009-03-24 Impact factor: 12.531
Authors: Charles M Balch; Jeffrey E Gershenwald; Seng-Jaw Soong; John F Thompson; Michael B Atkins; David R Byrd; Antonio C Buzaid; Alistair J Cochran; Daniel G Coit; Shouluan Ding; Alexander M Eggermont; Keith T Flaherty; Phyllis A Gimotty; John M Kirkwood; Kelly M McMasters; Martin C Mihm; Donald L Morton; Merrick I Ross; Arthur J Sober; Vernon K Sondak Journal: J Clin Oncol Date: 2009-11-16 Impact factor: 44.544
Authors: Yian Ann Chen; Jamie K Teer; Zeynep Eroglu; Jheng-Yu Wu; John M Koomen; Florian A Karreth; Jane L Messina; Keiran S M Smalley Journal: Semin Cancer Biol Date: 2019-11-02 Impact factor: 15.707
Authors: Katarzyna C Pituch; Markella Zannikou; Liliana Ilut; Ting Xiao; Michael Chastkofsky; Madina Sukhanova; Nicola Bertolino; Daniele Procissi; Christina Amidei; Craig M Horbinski; Karen S Aboody; C David James; Maciej S Lesniak; Irina V Balyasnikova Journal: Proc Natl Acad Sci U S A Date: 2021-03-02 Impact factor: 11.205
Authors: Dimitri G Trembath; Anastasia Ivanova; Michal T Krauze; John M Kirkwood; Nana Nikolaishvilli-Feinberg; Stergios J Moschos Journal: Melanoma Res Date: 2021-06-01 Impact factor: 3.199
Authors: Stergios J Moschos; Zeynep Eroglu; Nikhil I Khushalani; Kari L Kendra; George Ansstas; Gino K In; Peng Wang; Glenn Liu; Frances A Collichio; Paul B Googe; Craig C Carson; Karen McKinnon; Hsing-Hui Wang; Nana Nikolaishvilli-Feinberg; Anastasia Ivanova; Christy C Arrowood; Nancy Garrett-Mead; Kathleen C Conway; Sharon N Edmiston; David W Ollila; Jonathan S Serody; Nancy E Thomas; S Percy Ivy; Lokesh Agrawal; Elizabeth C Dees; James L Abbruzzese Journal: Melanoma Res Date: 2021-04-01 Impact factor: 3.199
Authors: Marco Tucci; Anna Passarelli; Francesco Mannavola; Claudia Felici; Luigia Stefania Stucci; Mauro Cives; Francesco Silvestris Journal: Front Oncol Date: 2019-11-05 Impact factor: 6.244