Küçük hücreli dışı akciğer karsinomlarında tümör ilişkili makrofajların tümör progresyonundaki rolü

Merih Tepeoğlu; F.zeynep Taştepe; B.handan Özdemir

doi:10.19161/etd.415007

EN TR

The role of tumor-associated macrophages on tumor progression in non-small cell lung carcinoma

Abstract

Aim: Lung cancer remains the leading cause of cancer-related mortality in all over the world. Non-small cell lung cancer (NSCLC) is the most frequent type of lung carcinoma. In the current study, the effects of tumor-associated macrophages (TAM) on tumor progression and metastasis in NSCLC were investigated.

Materials and Methods: Eighty NSCLC cases, which were diagnosed in Başkent University Medical School, Department of Pathology between January 2011 and May 2016 were included into the study. Clinical follow-up findings of the patients were recorded and CD68 immunohistochemistry was performed to all of them.

Results: Histologically, 36 cases (45%) were squamous cell carcinoma, 36 cases (45%) were adenocarcinoma, 6 cases (7.5%) were large cell carcinoma, and 2 cases were adenosquamous carcinoma (2.5%). The density of TAM in tumor tissue was 1+ in 28 cases (35%), 2+ in 21 cases (26.3%) and 3+ in 31 (38.8%) cases by immunohistochemistry. In addition, the density of TAM was 3+ in only 1 (3.1%) of 32 stage 1 patients, 17 (53.1%) of 32 stage 2 and 13 (81.3%) of 16 stage 3 and 4 patients had 3+ TAM density. The average survival was 39.7±17.4 months, 36.6±17.1 months and 27.3±18.4 months respectively (p<0.05), in the the patients who had 1+, 2+ and 3+ TAM density.

Conclusion: In the current study, we detected that the number of TAM is higher in NSCLC patients who had higher pathological T and TNM stage. Also, an average survival of the patients who had a higher number of TAM was shorter than the patients who had a lower number of TAM.

Keywords

Lung,non-small cell lung carcinoma,tumor-associated macrophages.

Küçük hücreli dışı akciğer karsinomlarında tümör ilişkili makrofajların tümör progresyonundaki rolü

Öz

Amaç: Akciğer kanseri tüm dünyada kanserden ölümlerin en sık sebebidir. Küçük hücreli dışı akciğer karsinomları (KHDAK) da en sık görülen akciğer kanser tipidir. Bu çalışmada küçük hücreli dışı akciğer karsinomlarında, tümör ilişkili makrofajların (TAM) tümör progresyonu ve metastaz üzerindeki etkileri araştırıldı.

Gereç ve Yöntem: Ocak 2011 ile Mayıs 2016 tarihleri arasında Başkent Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalında KHDAK tanısı alan 80 olgu çalışmaya dahil edildi. Olguların klinik takip bulguları kaydedildi ve tüm olgulara immünhistokimyasal olarak CD 68 antikoru uygulandı.

Bulgular: Olguların 36’sı (%45) skuamöz hücreli karsinom (SHK), 36’sı (%45) adenokarsinom, 6’sı (%7.5) büyük hücreli karsinom ve 2’si de (%%2.5) adenoskuamöz karsinom idi. Yapılan immünhistokimyasal çalışma sonucunda, 28 olgunun (%35) tümör dokusunda 1+, 21 olgunun (%26.3) tümör dokusunda 2+ ve 31 olgunun (%38.8) tümör dokusunda ise 3+ TAM yoğunluğu izlendi. Evre 1 olan 32 hastanın yalnızca 1 tanesi (%3.1) 3+ TAM yoğunluğuna sahipken, evre 2 olan 32 hastanın 17’sinde (%53.1) ve evre 3+4 olan 16 hastanın ise 13’ünde (%81.3) 3+ TAM yoğunluğu saptandı. TAM yoğunluğu 1+ olan hastaların ortalama yaşam ömrü 39.7±17.4 ay iken, TAM yoğunluğu 2+ olan hastaların 36.6±17.1 ay ve TAM yoğunluğu 3+ olan hastaların ise 27.3±18.4 aydı (p<0.05).

Sonuç: Bu çalışmada, patolojik T evresi ve TNM evresi yüksek olan KHDAK’da TAM sayısının daha yüksek olduğu görüldü ve yüksek TAM sayısı olan hastaların ortalama sağkalım süresinin de, düşük TAM sayısı olan hastaların sağkalım süresinden kısa olduğu saptandı.

Anahtar Kelimeler

Akciğer,küçük hücreli dışı akciğer karsinomu,tümör ilişkili makrofaj.

References

Travis DW, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. IARCPress; Lyon;2015:9-26.
Siegel RL, Miller KD, Jemal A. Cancer statistics 2015. CA Cancer J Clin 2015;65(1):5-29.
Rothschild SI. Targeted therapies in non-small cell lung cancer—beyond EGFR and ALK. Cancers 2015;7(2):930-49. Mantovani A, Sica A. Macrophages innate immunity and cancer: Balance, tolerance, and diversity. Curr Opin Immunol 2010;22(2):231-7.
Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages; effectors of angiogenesis and tumor progression. Biochim Biophys Acta 2009;1796(1):11-8.
Noy R, Pollard JW. Tumor-associated macrophages: From mechanisms to therapy. Immunity 2014;41(1):49-61.
Becker M, Müller CB, De Bastiani MA, Klannt F. The prognostic impact of tumor-associated macrophages and intra-tumoral apoptosis in non-small cell lung cancer. Histol Histopathol 2014;29(1): 21-31.
Solinas G, Germano G, Mantovani A, Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 2009;86(5):1065-73.
Forssell J, Oberg A, Henriksson ML, Stenling R, Jun A, Palmqvist R. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res 2007;13(5):1472-9.

Zhou Q, Peng RQ, Wu XJ, et al. The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer. J Transl Med 2010;8(13):1-9.
Wan T, Liu JH, Zheng LM, Cai MY, Ding T. Prognostic significance of tumor associated macrophage infiltration in advanced epithelial ovarian carcinoma. Chin J Cancer 2009;28(3):323-7.
Liu J, Li Z, Cui J, Xu G, Cui G. Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas. Tumour Biol 2012;33(2):495-505.
Hanada T, Nakagawa M, Emoto A, Nomura T, Nasu N, Nomura Y. Prognostic value of tumor-associated macrophage count in human bladder cancer. Int J Urol 2000;7(7):263-9.
Torisu H, Ono M, Kiryu H, et al. Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNF alpha and IL-1 alpha. Int J Cancer 2000;85(2):182-8.
Zhang QW, Liu L, Gong CY, et al. Prognostic significance of tumor associated macrophages in solid tumor: A meta-analysis of the literature. PLoS One 2012;7(12):1-14.
Zhang B, Yao G, Zhang Y, et al. M2-Polarized tumor associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma. Clinics 2011;66(11):1879-86.
Arenberg DA, Keane MP, DiGiovine B, et al. Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines. Cancer Immunol Immunother 2000;49(2):63-70.
Chen JJ, Yao PL, Yuan A, et al. Up-Regulation of tumor interleukin-8 expression by infiltrating macrophages its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin Cancer Res 2003;9(2):729-37.
da Costa Souza P, Parra ER, Atanazio MJ, et al. Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma. Histopathology 2012;61(4):487-596.
Kim D, Min H, Lee K, et al. High tumour islet macrophage infiltration correlates with improved patient survival but not with EGFR mutations, gene copy number or protein expression in resected non-small cell lung cancer. Br J Cancer 2008;98(6):1118-24. Toomey D, Smyth G, Condron C, et al. Infiltrating immune cells, but not tumour cells, Express FasL in non-small cell lung cancer: No association with prognosis identified in 3-year follow-up. Int J Cancer 2003;103(3):408-12.
Liss C, Fekete MJ, Hasina R, Lam CD, Lingen MW. Paracrine angiogenic loop between head-and-neck squamous-cell carcinomas and macrophages. Int J Cancer 2001;93(6):781-5.

Details

Primary Language

Turkish

Subjects

-

Journal Section

Research Article

Authors

Merih Tepeoğlu ^*
0000-0002-9894-8005
Türkiye

F.zeynep Taştepe
0000-0001-7149-6443
Türkiye

B.handan Özdemir
0000-0002-7528-3557
Türkiye

Publication Date

June 1, 2018

Submission Date

March 22, 2017

Acceptance Date

May 30, 2017

Published in Issue

Year 2018 Volume: 57 Number: 2

DOI

https://doi.org/10.19161/etd.415007

IZ

https://izlik.org/JA26RY37UN

Cite

RIS / Bibtex

Vancouver

1.Merih Tepeoğlu, F.zeynep Taştepe, B.handan Özdemir. Küçük hücreli dışı akciğer karsinomlarında tümör ilişkili makrofajların tümör progresyonundaki rolü. EJM. 2018 Jun. 1;57(2):107-12. doi:10.19161/etd.415007