Skip to main content
Top
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes – an immunohistochemical study

Authors: Falk Wehrhan, Maike Büttner-Herold, Peter Hyckel, Patrick Moebius, Raimund Preidl, Luitpold Distel, Jutta Ries, Kerstin Amann, Christian Schmitt, Friedrich W Neukam, Manuel Weber

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

It is largely accepted that specific immunological parameters in solid malignancies are associated with patient’s prognosis. Recently a correlation of macrophage polarization with histomorphological parameters could also be shown in oral squamous cell carcinoma (oscc). The observed tumor derived peripheral immune tolerance could be associated with the macrophage polarization in regional tumor draining lymph nodes.
So far there are no studies analyzing the macrophage polarization in cervical lymph nodes of oscc patients. In the present study we aimed to correlate macrophage polarization in different anatomical lymph node compartments of patients diagnosed with oscc with histopathologic parameters of the primary tumor (T-, N-, L-, V-, Pn-status, grading).

Methods

Tumor free (n = 37) and metastatic (n = 17) lymph nodes of T1 and T2 oscc patients were processed for immunohistochemistry to detect CD68, CD11c, CD163 and MRC1 positive cells. Samples were digitized using whole slide imaging and the number of cells expressing the aforementioned markers in the region of interest quantitatively analyzed.

Results

The malignancy of the primary tumor (defined by T-, L-, Pn-status, grading) correlated with the lymph node macrophage polarization. L1 and Pn1 tumor cases displayed a significantly (p < 0.05) decreased M1 and increased M2 polarization in the sinus of the lymph nodes. G3 cases presented a significantly (p < 0.05) increased M2 polarization in the sinus compared to G2 cases. T2 tumors had significantly (p < 0.05) increased M2 polarization in the interfollicular zone of regional lymph nodes compared to T1 tumors. Metastatic and non-metastatic lymph nodes did not differ regarding their macrophage polarization.

Conclusions

The current study revealed for the first time an influence of oscc on the macrophage polarization in regional lymph nodes. Markers of malignant behavior in the primary tumor were associated with a shift of macrophage polarization in lymph nodes from the anti-tumoral M1 type to the tumor-promoting M2 type. As tumor free and metastatic lymph nodes did not differ in terms of their macrophage polarization pattern, there must be other factors influencing the location for lymph node metastasis formation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Shaw RJ, Pace-Balzan A, Butterworth C: Contemporary clinical management of oral squamous cell carcinoma. Periodontol. 2011, 57 (1): 89-101.CrossRef Shaw RJ, Pace-Balzan A, Butterworth C: Contemporary clinical management of oral squamous cell carcinoma. Periodontol. 2011, 57 (1): 89-101.CrossRef
2.
go back to reference Scully C, Bagan J: Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis. 2009, 15 (6): 388-399.CrossRefPubMed Scully C, Bagan J: Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis. 2009, 15 (6): 388-399.CrossRefPubMed
3.
go back to reference Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009, 45 (4–5): 309-316.CrossRefPubMed Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009, 45 (4–5): 309-316.CrossRefPubMed
4.
go back to reference Kumagai K, Hamada Y, Gotoh A, Kobayashi H, Kawaguchi K, Horie A, Yamada H, Suzuki S, Suzuki R: Evidence for the changes of antitumor immune response during lymph node metastasis in head and neck squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010, 110 (3): 341-350.CrossRefPubMed Kumagai K, Hamada Y, Gotoh A, Kobayashi H, Kawaguchi K, Horie A, Yamada H, Suzuki S, Suzuki R: Evidence for the changes of antitumor immune response during lymph node metastasis in head and neck squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010, 110 (3): 341-350.CrossRefPubMed
5.
go back to reference Weber W, Reuther J, Muhling J, Ordung R, Michel C: [Statistical results in patients with squamous cell cancer of the mouth, 1981–1990 patient sample]. Fortschr Kiefer Gesichtschir. 1992, 37: 33-36.PubMed Weber W, Reuther J, Muhling J, Ordung R, Michel C: [Statistical results in patients with squamous cell cancer of the mouth, 1981–1990 patient sample]. Fortschr Kiefer Gesichtschir. 1992, 37: 33-36.PubMed
6.
go back to reference Fan S, Tang QL, Lin YJ, Chen WL, Li JS, Huang ZQ, Yang ZH, Wang YY, Zhang DM, Wang HJ, Dias-Ribeiro E, Cai Q, Wang L: A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma. Int J Oral Sci. 2011, 3 (4): 180-191.CrossRefPubMedPubMedCentral Fan S, Tang QL, Lin YJ, Chen WL, Li JS, Huang ZQ, Yang ZH, Wang YY, Zhang DM, Wang HJ, Dias-Ribeiro E, Cai Q, Wang L: A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma. Int J Oral Sci. 2011, 3 (4): 180-191.CrossRefPubMedPubMedCentral
7.
go back to reference Lingen MW, Kalmar JR, Karrison T, Speight PM: Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol. 2008, 44 (1): 10-22.CrossRefPubMed Lingen MW, Kalmar JR, Karrison T, Speight PM: Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol. 2008, 44 (1): 10-22.CrossRefPubMed
8.
go back to reference Hyckel P, Metzner G, Muller P, Haroske D, Quade R: [The significance of immunologic parameters for preoperative prognostication in carcinoma of the mouth]. Dtsch Z Mund Kiefer Gesichtschir. 1985, 9 (6): 461-468.PubMed Hyckel P, Metzner G, Muller P, Haroske D, Quade R: [The significance of immunologic parameters for preoperative prognostication in carcinoma of the mouth]. Dtsch Z Mund Kiefer Gesichtschir. 1985, 9 (6): 461-468.PubMed
9.
go back to reference Bier J, Nicklisch U: [Cellular and humoral immune reactivity in patients with squamous cell carcinoma of the oral cavity]. Dtsch Zahnarztl Z. 1977, 32 (10): 804-807.PubMed Bier J, Nicklisch U: [Cellular and humoral immune reactivity in patients with squamous cell carcinoma of the oral cavity]. Dtsch Zahnarztl Z. 1977, 32 (10): 804-807.PubMed
10.
go back to reference Metelmann HR, Hyckel P, Podmelle F: Oral cancer treatment and immune targets - a role for dendritic cells?. J Craniomaxillofac Surg. 2012, 40 (2): 103-104.CrossRefPubMed Metelmann HR, Hyckel P, Podmelle F: Oral cancer treatment and immune targets - a role for dendritic cells?. J Craniomaxillofac Surg. 2012, 40 (2): 103-104.CrossRefPubMed
11.
go back to reference Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F, Sakoda M, Ueno S, Natsugoe S, Takao S: Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res. 2011, 167 (2): e211-219.CrossRefPubMed Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F, Sakoda M, Ueno S, Natsugoe S, Takao S: Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res. 2011, 167 (2): e211-219.CrossRefPubMed
12.
go back to reference Mantovani A, Allavena P, Sica A, Balkwill F: Cancer-related inflammation. Nature. 2008, 454 (7203): 436-444.CrossRefPubMed Mantovani A, Allavena P, Sica A, Balkwill F: Cancer-related inflammation. Nature. 2008, 454 (7203): 436-444.CrossRefPubMed
13.
go back to reference Rauser S, Langer R, Tschernitz S, Gais P, Jutting U, Feith M, Hofler H, Walch A: High number of CD45RO + tumor infiltrating lymphocytes is an independent prognostic factor in non-metastasized (stage I-IIA) esophageal adenocarcinoma. BMC Cancer. 2010, 10: 608-CrossRefPubMedPubMedCentral Rauser S, Langer R, Tschernitz S, Gais P, Jutting U, Feith M, Hofler H, Walch A: High number of CD45RO + tumor infiltrating lymphocytes is an independent prognostic factor in non-metastasized (stage I-IIA) esophageal adenocarcinoma. BMC Cancer. 2010, 10: 608-CrossRefPubMedPubMedCentral
14.
go back to reference Grotz TE, Mansfield AS, Jakub JW, Markovic SN: Regional lymphatic immunity in melanoma. Melanoma Res. 2012, 22 (1): 9-18.CrossRefPubMed Grotz TE, Mansfield AS, Jakub JW, Markovic SN: Regional lymphatic immunity in melanoma. Melanoma Res. 2012, 22 (1): 9-18.CrossRefPubMed
15.
go back to reference Mao Y, Poschke I, Wennerberg E, de Pico Coana Y, Egyhazi Brage S, Schultz I, Hansson J, Masucci G, Lundqvist A, Kiessling R: Melanoma-educated CD14+ cells acquire a myeloid-derived suppressor cell phenotype through COX-2-dependent mechanisms. Cancer Res. 2013, 73 (13): 3877-3887.CrossRefPubMed Mao Y, Poschke I, Wennerberg E, de Pico Coana Y, Egyhazi Brage S, Schultz I, Hansson J, Masucci G, Lundqvist A, Kiessling R: Melanoma-educated CD14+ cells acquire a myeloid-derived suppressor cell phenotype through COX-2-dependent mechanisms. Cancer Res. 2013, 73 (13): 3877-3887.CrossRefPubMed
16.
go back to reference Swartz MA, Lund AW: Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nat Rev Cancer. 2012, 12 (3): 210-219.CrossRefPubMed Swartz MA, Lund AW: Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nat Rev Cancer. 2012, 12 (3): 210-219.CrossRefPubMed
17.
go back to reference Watanabe Y, Katou F, Ohtani H, Nakayama T, Yoshie O, Hashimoto K: Tumor-infiltrating lymphocytes, particularly the balance between CD8(+) T cells and CCR4(+) regulatory T cells, affect the survival of patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010, 109 (5): 744-752.CrossRefPubMed Watanabe Y, Katou F, Ohtani H, Nakayama T, Yoshie O, Hashimoto K: Tumor-infiltrating lymphocytes, particularly the balance between CD8(+) T cells and CCR4(+) regulatory T cells, affect the survival of patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010, 109 (5): 744-752.CrossRefPubMed
18.
go back to reference Shah W, Yan X, Jing L, Zhou Y, Chen H, Wang Y: A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4 (+) FOXP3 (+) regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix. Cell Mol Immunol. 2011, 8 (1): 59-66.CrossRefPubMed Shah W, Yan X, Jing L, Zhou Y, Chen H, Wang Y: A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4 (+) FOXP3 (+) regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix. Cell Mol Immunol. 2011, 8 (1): 59-66.CrossRefPubMed
19.
go back to reference Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, Hiraoka N: Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer. 2013, 108 (4): 914-923.CrossRefPubMedPubMedCentral Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, Hiraoka N: Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer. 2013, 108 (4): 914-923.CrossRefPubMedPubMedCentral
20.
go back to reference Balermpas P, Michel Y, Wagenblast J, Seitz O, Weiss C, Rodel F, Rodel C, Fokas E: Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer. Br J Cancer. 2014, 110 (2): 501-509.CrossRefPubMed Balermpas P, Michel Y, Wagenblast J, Seitz O, Weiss C, Rodel F, Rodel C, Fokas E: Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer. Br J Cancer. 2014, 110 (2): 501-509.CrossRefPubMed
21.
go back to reference Costa NL, Valadares MC, Souza PP, Mendonca EF, Oliveira JC, Silva TA, Batista AC: Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma. Oral Oncol. 2012 Costa NL, Valadares MC, Souza PP, Mendonca EF, Oliveira JC, Silva TA, Batista AC: Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma. Oral Oncol. 2012
22.
go back to reference El-Rouby DH: Association of macrophages with angiogenesis in oral verrucous and squamous cell carcinomas. J Oral Pathol Med. 2010, 39 (7): 559-564.CrossRefPubMed El-Rouby DH: Association of macrophages with angiogenesis in oral verrucous and squamous cell carcinomas. J Oral Pathol Med. 2010, 39 (7): 559-564.CrossRefPubMed
23.
go back to reference Fujii N, Shomori K, Shiomi T, Nakabayashi M, Takeda C, Ryoke K, Ito H: Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance. J Oral Pathol Med. 2012, 41 (6): 444-451.CrossRefPubMed Fujii N, Shomori K, Shiomi T, Nakabayashi M, Takeda C, Ryoke K, Ito H: Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance. J Oral Pathol Med. 2012, 41 (6): 444-451.CrossRefPubMed
24.
go back to reference Lu CF, Huang CS, Tjiu JW, Chiang CP: Infiltrating macrophage count: a significant predictor for the progression and prognosis of oral squamous cell carcinomas in Taiwan. Head Neck. 2010, 32 (1): 18-25.PubMed Lu CF, Huang CS, Tjiu JW, Chiang CP: Infiltrating macrophage count: a significant predictor for the progression and prognosis of oral squamous cell carcinomas in Taiwan. Head Neck. 2010, 32 (1): 18-25.PubMed
25.
go back to reference Tong CC, Kao J, Sikora AG: Recognizing and reversing the immunosuppressive tumor microenvironment of head and neck cancer. Immunol Res. 2012, 54 (1–3): 266-274.CrossRefPubMed Tong CC, Kao J, Sikora AG: Recognizing and reversing the immunosuppressive tumor microenvironment of head and neck cancer. Immunol Res. 2012, 54 (1–3): 266-274.CrossRefPubMed
26.
go back to reference Weber M, Buttner-Herold M, Hyckel P, Moebius P, Distel L, Ries J, Amann K, Neukam FW, Wehrhan F: Small oral squamous cell carcinomas with nodal lymphogenic metastasis show increased infiltration of M2 polarized macrophages - An immunohistochemical analysis. J Craniomaxillofac Surg. 2014 Weber M, Buttner-Herold M, Hyckel P, Moebius P, Distel L, Ries J, Amann K, Neukam FW, Wehrhan F: Small oral squamous cell carcinomas with nodal lymphogenic metastasis show increased infiltration of M2 polarized macrophages - An immunohistochemical analysis. J Craniomaxillofac Surg. 2014
27.
go back to reference Vu HL, Sikora AG, Fu S, Kao J: HPV-induced oropharyngeal cancer, immune response and response to therapy. Cancer Lett. 2010, 288 (2): 149-155.CrossRefPubMed Vu HL, Sikora AG, Fu S, Kao J: HPV-induced oropharyngeal cancer, immune response and response to therapy. Cancer Lett. 2010, 288 (2): 149-155.CrossRefPubMed
28.
go back to reference Ward MJ, Thirdborough SM, Mellows T, Riley C, Harris S, Suchak K, Webb A, Hampton C, Patel NN, Randall CJ, Cox HJ, Jogai S, Primrose J, Piper K, Ottensmeier CH, King EV, Thomas GJ: Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. Br J Cancer. 2014, 110 (2): 489-500.CrossRefPubMed Ward MJ, Thirdborough SM, Mellows T, Riley C, Harris S, Suchak K, Webb A, Hampton C, Patel NN, Randall CJ, Cox HJ, Jogai S, Primrose J, Piper K, Ottensmeier CH, King EV, Thomas GJ: Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. Br J Cancer. 2014, 110 (2): 489-500.CrossRefPubMed
29.
go back to reference Mantovani A, Sica A, Locati M: New vistas on macrophage differentiation and activation. Eur J Immunol. 2007, 37 (1): 14-16.CrossRefPubMed Mantovani A, Sica A, Locati M: New vistas on macrophage differentiation and activation. Eur J Immunol. 2007, 37 (1): 14-16.CrossRefPubMed
30.
go back to reference Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M: Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2013, 229 (2): 176-185.CrossRefPubMed Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M: Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2013, 229 (2): 176-185.CrossRefPubMed
32.
go back to reference Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C, Higashida M, Mikasa H, Nakaya Y, Takanashi S, Igarashi T, Kitagawa T, Sata M: Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. J Am Coll Cardiol. 2011, 58 (3): 248-255.CrossRefPubMed Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C, Higashida M, Mikasa H, Nakaya Y, Takanashi S, Igarashi T, Kitagawa T, Sata M: Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. J Am Coll Cardiol. 2011, 58 (3): 248-255.CrossRefPubMed
33.
go back to reference Cao X, Shen D, Patel MM, Tuo J, Johnson TM, Olsen TW, Chan CC: Macrophage polarization in the maculae of age-related macular degeneration: A pilot study. Pathol Int. 2011, 61 (9): 528-535.CrossRefPubMedPubMedCentral Cao X, Shen D, Patel MM, Tuo J, Johnson TM, Olsen TW, Chan CC: Macrophage polarization in the maculae of age-related macular degeneration: A pilot study. Pathol Int. 2011, 61 (9): 528-535.CrossRefPubMedPubMedCentral
35.
go back to reference Cho KY, Miyoshi H, Kuroda S, Yasuda H, Kamiyama K, Nakagawara J, Takigami M, Kondo T, Atsumi T: The Phenotype of Infiltrating Macrophages Influences Arteriosclerotic Plaque Vulnerability in the Carotid Artery. J Stroke Cerebrovasc Dis. 2012 Cho KY, Miyoshi H, Kuroda S, Yasuda H, Kamiyama K, Nakagawara J, Takigami M, Kondo T, Atsumi T: The Phenotype of Infiltrating Macrophages Influences Arteriosclerotic Plaque Vulnerability in the Carotid Artery. J Stroke Cerebrovasc Dis. 2012
36.
go back to reference Kawamura K, Komohara Y, Takaishi K, Katabuchi H, Takeya M: Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol Int. 2009, 59 (5): 300-305.CrossRefPubMed Kawamura K, Komohara Y, Takaishi K, Katabuchi H, Takeya M: Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol Int. 2009, 59 (5): 300-305.CrossRefPubMed
37.
go back to reference Pejnovic N, Pantic J, Jovanovic I, Radosavljevic G, Milovanovic M, Nikolic I, Zdravkovic N, Djukic A, Arsenijevic N, Lukic M: Galectin-3 Deficiency Accelerates High-Fat Diet Induced Obesity and Amplifies Inflammation in Adipose Tissue and Pancreatic Islets. Diabetes. 2013, 62: 1932-1944.CrossRefPubMedPubMedCentral Pejnovic N, Pantic J, Jovanovic I, Radosavljevic G, Milovanovic M, Nikolic I, Zdravkovic N, Djukic A, Arsenijevic N, Lukic M: Galectin-3 Deficiency Accelerates High-Fat Diet Induced Obesity and Amplifies Inflammation in Adipose Tissue and Pancreatic Islets. Diabetes. 2013, 62: 1932-1944.CrossRefPubMedPubMedCentral
38.
go back to reference Fischer-Posovszky P, Wang QA, Asterholm IW, Rutkowski JM, Scherer PE: Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages. Endocrinology. 2011, 152 (8): 3074-3081.CrossRefPubMedPubMedCentral Fischer-Posovszky P, Wang QA, Asterholm IW, Rutkowski JM, Scherer PE: Targeted deletion of adipocytes by apoptosis leads to adipose tissue recruitment of alternatively activated M2 macrophages. Endocrinology. 2011, 152 (8): 3074-3081.CrossRefPubMedPubMedCentral
39.
go back to reference Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A, Aissat A, Guerre-Millo M, Clement K: Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab. 2009, 94 (11): 4619-4623.CrossRefPubMed Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A, Aissat A, Guerre-Millo M, Clement K: Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab. 2009, 94 (11): 4619-4623.CrossRefPubMed
40.
go back to reference Hasan D, Chalouhi N, Jabbour P, Hashimoto T: Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results. J Neuroinflammation. 2012, 9: 222-CrossRefPubMedPubMedCentral Hasan D, Chalouhi N, Jabbour P, Hashimoto T: Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results. J Neuroinflammation. 2012, 9: 222-CrossRefPubMedPubMedCentral
41.
go back to reference van Putten SM, Ploeger DT, Popa ER, Bank RA: Macrophage phenotypes in the collagen-induced foreign body reaction in rats. Acta Biomater. 2013, 6502: 10- van Putten SM, Ploeger DT, Popa ER, Bank RA: Macrophage phenotypes in the collagen-induced foreign body reaction in rats. Acta Biomater. 2013, 6502: 10-
42.
go back to reference Lan C, Huang X, Lin S, Huang H, Cai Q, Wan T, Lu J, Liu J: Expression of M2-Polarized Macrophages is Associated with Poor Prognosis for Advanced Epithelial Ovarian Cancer. Technol Cancer Res Treat. 2012 Lan C, Huang X, Lin S, Huang H, Cai Q, Wan T, Lu J, Liu J: Expression of M2-Polarized Macrophages is Associated with Poor Prognosis for Advanced Epithelial Ovarian Cancer. Technol Cancer Res Treat. 2012
43.
go back to reference Herwig MC, Bergstrom C, Wells JR, Holler T, Grossniklaus HE: M2/M1 ratio of tumor associated macrophages and PPAR-gamma expression in uveal melanomas with class 1 and class 2 molecular profiles. Exp Eye Res. 2013, 107: 52-58.CrossRefPubMed Herwig MC, Bergstrom C, Wells JR, Holler T, Grossniklaus HE: M2/M1 ratio of tumor associated macrophages and PPAR-gamma expression in uveal melanomas with class 1 and class 2 molecular profiles. Exp Eye Res. 2013, 107: 52-58.CrossRefPubMed
44.
go back to reference O'Brien CJ, Lauer CS, Fredricks S, Clifford AR, McNeil EB, Bagia JS, Koulmandas C: Tumor thickness influences prognosis of T1 and T2 oral cavity cancer–but what thickness?. Head Neck. 2003, 25 (11): 937-945.CrossRefPubMed O'Brien CJ, Lauer CS, Fredricks S, Clifford AR, McNeil EB, Bagia JS, Koulmandas C: Tumor thickness influences prognosis of T1 and T2 oral cavity cancer–but what thickness?. Head Neck. 2003, 25 (11): 937-945.CrossRefPubMed
45.
go back to reference Lanzer M, Gander T, Kruse A, Luebbers HT, Reinisch S: Influence of histopathologic factors on pattern of metastasis in squamous cell carcinoma of the head and neck. Laryngoscope. 2013 Lanzer M, Gander T, Kruse A, Luebbers HT, Reinisch S: Influence of histopathologic factors on pattern of metastasis in squamous cell carcinoma of the head and neck. Laryngoscope. 2013
46.
go back to reference Fagan JJ, Collins B, Barnes L, D'Amico F, Myers EN, Johnson JT: Perineural invasion in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 1998, 124 (6): 637-640.CrossRefPubMed Fagan JJ, Collins B, Barnes L, D'Amico F, Myers EN, Johnson JT: Perineural invasion in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 1998, 124 (6): 637-640.CrossRefPubMed
47.
go back to reference Fortin A, Couture C, Doucet R, Albert M, Allard J, Tetu B: Does histologic grade have a role in the management of head and neck cancers?. J Clin Oncol. 2001, 19 (21): 4107-4116.PubMed Fortin A, Couture C, Doucet R, Albert M, Allard J, Tetu B: Does histologic grade have a role in the management of head and neck cancers?. J Clin Oncol. 2001, 19 (21): 4107-4116.PubMed
48.
go back to reference Carinci F, Pelucchi S, Farina A, De Franciscis G, Calearo C: Extension as a prognostic factor in oropharyngeal cancer: largest mucosal dimension compared with number of (sub) sites involved. Br J Oral Maxillofac Surg. 1998, 36 (6): 440-445.CrossRefPubMed Carinci F, Pelucchi S, Farina A, De Franciscis G, Calearo C: Extension as a prognostic factor in oropharyngeal cancer: largest mucosal dimension compared with number of (sub) sites involved. Br J Oral Maxillofac Surg. 1998, 36 (6): 440-445.CrossRefPubMed
49.
go back to reference Mansfield AS, Holtan SG, Grotz TE, Allred JB, Jakub JW, Erickson LA, Markovic SN: Regional immunity in melanoma: immunosuppressive changes precede nodal metastasis. Mod Pathol. 2011, 24 (4): 487-494.CrossRefPubMed Mansfield AS, Holtan SG, Grotz TE, Allred JB, Jakub JW, Erickson LA, Markovic SN: Regional immunity in melanoma: immunosuppressive changes precede nodal metastasis. Mod Pathol. 2011, 24 (4): 487-494.CrossRefPubMed
50.
51.
go back to reference Coleman R, Gnant M, Morgan G, Clezardin P: Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst. 2012, 104 (14): 1059-1067.CrossRefPubMed Coleman R, Gnant M, Morgan G, Clezardin P: Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst. 2012, 104 (14): 1059-1067.CrossRefPubMed
52.
go back to reference Ben-Aharon I, Vidal L, Rizel S, Yerushalmi R, Shpilberg O, Sulkes A, Stemmer SM: Bisphosphonates in the adjuvant setting of breast cancer therapy–effect on survival: a systematic review and meta-analysis. PLoS One. 2013, 8 (8): e70044-CrossRefPubMedPubMedCentral Ben-Aharon I, Vidal L, Rizel S, Yerushalmi R, Shpilberg O, Sulkes A, Stemmer SM: Bisphosphonates in the adjuvant setting of breast cancer therapy–effect on survival: a systematic review and meta-analysis. PLoS One. 2013, 8 (8): e70044-CrossRefPubMedPubMedCentral
54.
go back to reference Coscia M, Quaglino E, Iezzi M, Curcio C, Pantaleoni F, Riganti C, Holen I, Monkkonen H, Boccadoro M, Forni G, Musiani P, Bosia A, Cavallo F, Massaia M: Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med. 2010, 14 (12): 2803-2815.CrossRefPubMed Coscia M, Quaglino E, Iezzi M, Curcio C, Pantaleoni F, Riganti C, Holen I, Monkkonen H, Boccadoro M, Forni G, Musiani P, Bosia A, Cavallo F, Massaia M: Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med. 2010, 14 (12): 2803-2815.CrossRefPubMed
Metadata
Title
Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes – an immunohistochemical study
Authors
Falk Wehrhan
Maike Büttner-Herold
Peter Hyckel
Patrick Moebius
Raimund Preidl
Luitpold Distel
Jutta Ries
Kerstin Amann
Christian Schmitt
Friedrich W Neukam
Manuel Weber
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-522

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine