Nichita Luciana, Zurac Sabina, Bastian Alexandra, Stinga Patricia, Nedelcu Roxana, Brinzea Alice, Turcu Gabriela, Ion Daniela, Jilaveanu Lucia, Sticlaru Liana, Popp Cristiana, Cioplea Mirela
Department of Pathology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 010221 Bucharest, Romania.
Department of Pathology, Colentina University Hospital, 020125 Bucharest, Romania.
Oncol Lett. 2019 May;17(5):4149-4154. doi: 10.3892/ol.2019.10067. Epub 2019 Feb 25.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a key molecule in several intracellular and intercellular signaling pathways, with multiple functional and structural roles. CEACAM1 expression in melanoma is often described in the invading part of the tumor and has been associated with increased melanoma cells invasion and migration. We studied CEACAM1 expression in regressing versus non-regressing thin melanomas, knowing that phenomenon of regression represents a valuable model for understanding tumor immunity. In melanoma, through homophilic interactions, CEACAM1 inhibits natural killer cell activity, inhibits effector functions of tumor infiltrating lymphocytes, such as cytotoxicity and interferon-γ release. We present a retrospective study including 53 consecutive cases of thin melanoma, 21 with regression and 32 without regression. Comparative analysis of CEACAM1 expression in regressed and non-regressed areas from melanomas with regression and in non-regressed melanomas was performed. We used three different clones of CEACAM1: AA 1-428, extracellular domain, rabbit; AA 1-428, mouse, clone 8B6E2F4; and AA 1-468, full length, mouse, clone 2F6. All three clones had similar reactivity. We identified membrane positivity of tumor cells in non-regressed melanomas and in non-regressed areas in melanomas with regression. Remaining tumor cells in regressed areas were mostly negative for CEACAM1. In non-regressed lesions, there was a stronger positivity of CEACAM1 in the deep invasive front. In thin melanomas, CEACAM1 overexpression is related with invasiveness, suggesting that CEACAM1-positive melanomas are more aggressive. Also, in areas of regression tumor cells lose CEACAM1 expression, probably correlated with the presence of natural killer cells.
癌胚抗原相关细胞黏附分子1(CEACAM1)是多种细胞内和细胞间信号通路中的关键分子,具有多种功能和结构作用。黑色素瘤中CEACAM1的表达通常在肿瘤的侵袭部位被描述,并且与黑色素瘤细胞侵袭和迁移增加有关。我们研究了消退性与非消退性薄黑色素瘤中CEACAM1的表达情况,因为我们知道消退现象是理解肿瘤免疫的一个有价值的模型。在黑色素瘤中,通过同源相互作用,CEACAM1抑制自然杀伤细胞活性,抑制肿瘤浸润淋巴细胞的效应功能,如细胞毒性和干扰素-γ释放。我们进行了一项回顾性研究,纳入了53例连续的薄黑色素瘤病例,其中21例有消退,32例无消退。对有消退的黑色素瘤的消退区和非消退区以及无消退的黑色素瘤中CEACAM1的表达进行了比较分析。我们使用了三种不同的CEACAM1克隆:AA 1-428,细胞外结构域,兔源;AA 1-428,小鼠源,克隆8B6E2F4;以及AA 1-468,全长,小鼠源,克隆2F6。所有这三种克隆都具有相似的反应性。我们在无消退的黑色素瘤以及有消退的黑色素瘤的非消退区中鉴定出肿瘤细胞膜阳性。消退区剩余的肿瘤细胞大多CEACAM1呈阴性。在无消退的病变中,CEACAM1在深部侵袭前沿的阳性更强。在薄黑色素瘤中,CEACAM1过表达与侵袭性相关,表明CEACAM1阳性的黑色素瘤更具侵袭性。此外,在消退区域肿瘤细胞失去CEACAM1表达,这可能与自然杀伤细胞的存在有关。