Skip to main content
Erschienen in: Archives of Dermatological Research 1/2013

01.01.2013 | Original Paper

Expression of TLR3, 4, 7 and 9 in cutaneous malignant melanoma: relationship with clinicopathological characteristics and prognosis

verfasst von: N. Eiró, C. Ovies, B. Fernandez-Garcia, C. C. Álvarez-Cuesta, L. González, L. O. González, F. J. Vizoso

Erschienen in: Archives of Dermatological Research | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

Toll-like receptors (TLRs) have achieved an extraordinary amount of interest in cancer research due to their role in tumor progression. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, 7 and 9 in cutaneous malignant melanoma (CMM). The expression levels of TLR3, 4, 7 and 9 were analyzed in tumors from 30 patients with CMM. The analysis was performed by immunohistochemistry, and the results were correlated with various clinicopathological findings and with relapse-free survival. Our results indicate that there was a wide variability in the immunostaining score values for each receptor. Positive staining for TLRs was generally found in tumor cells, especially for TLR4 and TLR9. Nevertheless, a significant percentage of tumors also showed TLR4 expression in mononuclear inflammatory cells (62.1 %) and in fibroblast-like cells (34.5 %). Our results showed no significant association between score values for each TLR and clinicopathological characteristics of patients. However, our results demonstrated that high TLR4 expression was significantly associated with a shortened relapse-free survival (p = 0.001). Therefore, TLR4 expression may be a new prognostic factor of unfavorable evolution in cutaneous malignant melanoma.
Literatur
3.
Zurück zum Zitat Armstrong BK, Kricker A (1994) Cutaneous melanoma. Cancer Surv 19–20:219–240PubMed Armstrong BK, Kricker A (1994) Cutaneous melanoma. Cancer Surv 19–20:219–240PubMed
4.
Zurück zum Zitat Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27(36):6199–6206. doi:10.1200/JCO.2009.23.4799 PubMedCrossRef Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27(36):6199–6206. doi:10.​1200/​JCO.​2009.​23.​4799 PubMedCrossRef
6.
Zurück zum Zitat Bhattacharya D, Yusuf N (2012) Expression of toll-like receptors on breast tumors: taking a toll on tumor microenvironment. Int J Breast Cancer 2012:716564. doi:10.1155/2012/716564 PubMed Bhattacharya D, Yusuf N (2012) Expression of toll-like receptors on breast tumors: taking a toll on tumor microenvironment. Int J Breast Cancer 2012:716564. doi:10.​1155/​2012/​716564 PubMed
7.
8.
Zurück zum Zitat Breslow A, Macht SD (1978) Evaluation of prognosis in stage I cutaneous melanoma. Plast Reconstr Surg 61(3):342–346PubMedCrossRef Breslow A, Macht SD (1978) Evaluation of prognosis in stage I cutaneous melanoma. Plast Reconstr Surg 61(3):342–346PubMedCrossRef
9.
Zurück zum Zitat Brightling CE, Ammit AJ, Kaur D, Black JL, Wardlaw AJ, Hughes JM, Bradding P (2005) The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med 171(10):1103–1108. doi:10.1164/rccm.200409-1220OC PubMedCrossRef Brightling CE, Ammit AJ, Kaur D, Black JL, Wardlaw AJ, Hughes JM, Bradding P (2005) The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med 171(10):1103–1108. doi:10.​1164/​rccm.​200409-1220OC PubMedCrossRef
10.
Zurück zum Zitat Cammarota R, Bertolini V, Pennesi G, Bucci EO, Gottardi O, Garlanda C, Laghi L, Barberis MC, Sessa F, Noonan DM, Albini A (2010) The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker. J Transl Med 8:112. doi:10.1186/1479-5876-8-112 PubMedCrossRef Cammarota R, Bertolini V, Pennesi G, Bucci EO, Gottardi O, Garlanda C, Laghi L, Barberis MC, Sessa F, Noonan DM, Albini A (2010) The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker. J Transl Med 8:112. doi:10.​1186/​1479-5876-8-112 PubMedCrossRef
12.
Zurück zum Zitat Cochran AJ (1997) Prediction of outcome for patients with cutaneous melanoma. Pigment Cell Res 10(3):162–167PubMedCrossRef Cochran AJ (1997) Prediction of outcome for patients with cutaneous melanoma. Pigment Cell Res 10(3):162–167PubMedCrossRef
16.
Zurück zum Zitat Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, Hsu D, Xu R, Harpaz N, Dannenberg AJ, Subbaramaiah K, Cooper HS, Itzkowitz SH, Abreu MT (2007) Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133(6):1869–1881. doi:10.1053/j.gastro.2007.09.008 PubMedCrossRef Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, Hsu D, Xu R, Harpaz N, Dannenberg AJ, Subbaramaiah K, Cooper HS, Itzkowitz SH, Abreu MT (2007) Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133(6):1869–1881. doi:10.​1053/​j.​gastro.​2007.​09.​008 PubMedCrossRef
17.
Zurück zum Zitat Gonzalez-Reyes S, Fernandez JM, Gonzalez LO, Aguirre A, Suarez A, Gonzalez JM, Escaff S, Vizoso FJ (2011) Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer Immunol Immunother 60(2):217–226. doi:10.1007/s00262-010-0931-0 PubMedCrossRef Gonzalez-Reyes S, Fernandez JM, Gonzalez LO, Aguirre A, Suarez A, Gonzalez JM, Escaff S, Vizoso FJ (2011) Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer Immunol Immunother 60(2):217–226. doi:10.​1007/​s00262-010-0931-0 PubMedCrossRef
18.
Zurück zum Zitat Gonzalez-Reyes S, Marin L, Gonzalez L, Gonzalez LO, del Casar JM, Lamelas ML, Gonzalez-Quintana JM, Vizoso FJ (2010) Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer 10:665. doi:10.1186/1471-2407-10-665 PubMedCrossRef Gonzalez-Reyes S, Marin L, Gonzalez L, Gonzalez LO, del Casar JM, Lamelas ML, Gonzalez-Quintana JM, Vizoso FJ (2010) Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer 10:665. doi:10.​1186/​1471-2407-10-665 PubMedCrossRef
19.
Zurück zum Zitat Goto Y, Arigami T, Kitago M, Nguyen SL, Narita N, Ferrone S, Morton DL, Irie RF, Hoon DS (2008) Activation of Toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors. Mol Cancer Ther 7(11):3642–3653. doi:10.1158/1535-7163.MCT-08-0582 PubMedCrossRef Goto Y, Arigami T, Kitago M, Nguyen SL, Narita N, Ferrone S, Morton DL, Irie RF, Hoon DS (2008) Activation of Toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors. Mol Cancer Ther 7(11):3642–3653. doi:10.​1158/​1535-7163.​MCT-08-0582 PubMedCrossRef
22.
Zurück zum Zitat Kaiser WJ, Kaufman JL, Offermann MK (2004) IFN-alpha sensitizes human umbilical vein endothelial cells to apoptosis induced by double-stranded RNA. J Immunol 172(3):1699–1710PubMed Kaiser WJ, Kaufman JL, Offermann MK (2004) IFN-alpha sensitizes human umbilical vein endothelial cells to apoptosis induced by double-stranded RNA. J Immunol 172(3):1699–1710PubMed
24.
Zurück zum Zitat Massi D, Borgognoni L, Franchi A, Martini L, Reali UM, Santucci M (2000) Thick cutaneous malignant melanoma: a reappraisal of prognostic factors. Melanoma Res 10(2):153–164PubMed Massi D, Borgognoni L, Franchi A, Martini L, Reali UM, Santucci M (2000) Thick cutaneous malignant melanoma: a reappraisal of prognostic factors. Melanoma Res 10(2):153–164PubMed
25.
Zurück zum Zitat Merrill RM, Feuer EJ (1996) Risk-adjusted cancer-incidence rates (United States). Cancer Causes Control 7(5):544–552PubMedCrossRef Merrill RM, Feuer EJ (1996) Risk-adjusted cancer-incidence rates (United States). Cancer Causes Control 7(5):544–552PubMedCrossRef
27.
28.
Zurück zum Zitat Miyake K (2007) Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 19:8CrossRef Miyake K (2007) Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 19:8CrossRef
29.
Zurück zum Zitat Morikawa T, Sugiyama A, Kume H, Ota S, Kashima T, Tomita K, Kitamura T, Kodama T, Fukayama M, Aburatani H (2007) Identification of Toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma. Clin Cancer Res 13(19):5703–5709. doi:10.1158/1078-0432.CCR-07-0603 PubMedCrossRef Morikawa T, Sugiyama A, Kume H, Ota S, Kashima T, Tomita K, Kitamura T, Kodama T, Fukayama M, Aburatani H (2007) Identification of Toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma. Clin Cancer Res 13(19):5703–5709. doi:10.​1158/​1078-0432.​CCR-07-0603 PubMedCrossRef
31.
Zurück zum Zitat Nikolova PN, Pawelec GP, Mihailova SM, Ivanova MI, Myhailova AP, Baltadjieva DN, Marinova DI, Ivanova SS, Naumova EJ (2007) Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population. Cancer Immunol Immunother 56(3):371–379. doi:10.1007/s00262-006-0193-z PubMedCrossRef Nikolova PN, Pawelec GP, Mihailova SM, Ivanova MI, Myhailova AP, Baltadjieva DN, Marinova DI, Ivanova SS, Naumova EJ (2007) Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population. Cancer Immunol Immunother 56(3):371–379. doi:10.​1007/​s00262-006-0193-z PubMedCrossRef
33.
Zurück zum Zitat Parker RL, Huntsman DG, Lesack DW, Cupples JB, Grant DR, Akbari M, Gilks CB (2002) Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. Am J Clin Pathol 117(5):723–728. doi:10.1309/PEF8-GL6F-YWMC-AG56 PubMedCrossRef Parker RL, Huntsman DG, Lesack DW, Cupples JB, Grant DR, Akbari M, Gilks CB (2002) Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. Am J Clin Pathol 117(5):723–728. doi:10.​1309/​PEF8-GL6F-YWMC-AG56 PubMedCrossRef
37.
Zurück zum Zitat Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176(8):4894–4901. doi:176/8/4894 PubMed Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176(8):4894–4901. doi:176/​8/​4894 PubMed
39.
Zurück zum Zitat Scarlett UK, Cubillos-Ruiz JR, Nesbeth YC, Martinez DG, Engle X, Gewirtz AT, Ahonen CL, Conejo-Garcia JR (2009) In situ stimulation of CD40 and Toll-like receptor 3 transforms ovarian cancer-infiltrating dendritic cells from immunosuppressive to immunostimulatory cells. Cancer Res 69(18):7329–7337. doi:10.1158/0008-5472.CAN-09-0835 PubMedCrossRef Scarlett UK, Cubillos-Ruiz JR, Nesbeth YC, Martinez DG, Engle X, Gewirtz AT, Ahonen CL, Conejo-Garcia JR (2009) In situ stimulation of CD40 and Toll-like receptor 3 transforms ovarian cancer-infiltrating dendritic cells from immunosuppressive to immunostimulatory cells. Cancer Res 69(18):7329–7337. doi:10.​1158/​0008-5472.​CAN-09-0835 PubMedCrossRef
41.
Zurück zum Zitat Shojaei H, Oberg HH, Juricke M, Marischen L, Kunz M, Mundhenke C, Gieseler F, Kabelitz D, Wesch D (2009) Toll-like receptors 3 and 7 agonists enhance tumor cell lysis by human gammadelta T cells. Cancer Res 69(22):8710–8717. doi:10.1158/0008-5472.CAN-09-1602 PubMedCrossRef Shojaei H, Oberg HH, Juricke M, Marischen L, Kunz M, Mundhenke C, Gieseler F, Kabelitz D, Wesch D (2009) Toll-like receptors 3 and 7 agonists enhance tumor cell lysis by human gammadelta T cells. Cancer Res 69(22):8710–8717. doi:10.​1158/​0008-5472.​CAN-09-1602 PubMedCrossRef
42.
Zurück zum Zitat Steinbrink K, Graulich E, Kubsch S, Knop J, Enk AH (2002) CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 99(7):2468–2476PubMedCrossRef Steinbrink K, Graulich E, Kubsch S, Knop J, Enk AH (2002) CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 99(7):2468–2476PubMedCrossRef
43.
Zurück zum Zitat Swerlick RA, Chen S (1997) The melanoma epidemic: more apparent than real? Mayo Clin Proc 72(6):559–564PubMedCrossRef Swerlick RA, Chen S (1997) The melanoma epidemic: more apparent than real? Mayo Clin Proc 72(6):559–564PubMedCrossRef
44.
Zurück zum Zitat Valins W, Amini S, Berman B (2010) The expression of Toll-like receptors in dermatological diseases and the therapeutic effect of current and newer topical Toll-like receptor modulators. J Clin Aesthet Dermatol 3(9):20–29 Valins W, Amini S, Berman B (2010) The expression of Toll-like receptors in dermatological diseases and the therapeutic effect of current and newer topical Toll-like receptor modulators. J Clin Aesthet Dermatol 3(9):20–29
Metadaten
Titel
Expression of TLR3, 4, 7 and 9 in cutaneous malignant melanoma: relationship with clinicopathological characteristics and prognosis
verfasst von
N. Eiró
C. Ovies
B. Fernandez-Garcia
C. C. Álvarez-Cuesta
L. González
L. O. González
F. J. Vizoso
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Archives of Dermatological Research / Ausgabe 1/2013
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-012-1300-y

Weitere Artikel der Ausgabe 1/2013

Archives of Dermatological Research 1/2013 Zur Ausgabe

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

26.04.2024 Hirsutismus Nachrichten

Laser- und Lichtbehandlungen können bei Frauen mit polyzystischem Ovarialsyndrom (PCOS) den übermäßigen Haarwuchs verringern und das Wohlbefinden verbessern – bei alleiniger Anwendung oder in Kombination mit Medikamenten.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

22.04.2024 DGIM 2024 Nachrichten

Um Menschen nach der Flucht aus einem Krisengebiet bestmöglich medizinisch betreuen zu können, ist es gut zu wissen, welche Erkrankungen im jeweiligen Herkunftsland häufig sind. Dabei hilft eine Internetseite der CDC (Centers for Disease Control and Prevention).

Kein Abstrich bei chronischen Wunden ohne Entzündungszeichen!

16.04.2024 DGIM 2024 Nachrichten

Den Reflex, eine oberflächliche chronische Hautwunde ohne Entzündungszeichen in jedem Fall abzustreichen, sollte man nach einer neuen „Klug-entscheiden“-Empfehlung unterdrücken.

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.