Rectum cancers with distant metastases (Stage IV) show decreased tissue expression of E cadherin at the invasive tumor front

Yıl 2020, Cilt: 53 Sayı: 1, 12 - 19, 31.03.2020

Mehmet Zengin , Pınar Atasoy

https://doi.org/10.20492/aeahtd.571124

Öz

Aim:
Rectal cancers (RC) are one of
the most cause of death worldwide. Survival of patients is
mainly associated with the TNM stage. However,
patients characterized by the same tumor stage often have prominent distinct
survival. This
is particularly a clinical challenge and new biomarkers are needed. In the
present research, we analyzed
the prognostic role of E-cadherin (EC) in stage IV RC.

Methods: Eighty-five
stage IV RC patients who underwent surgery at Kırıkkale University during
2001–2015 were included in this retrospective study. EC was scored on immunohistochemical
(IHC) stained sections with a
cut-off value of ≥50% ratio. The relationship between the
results and the clinicopathological characteristics was analyzed.

Results: EC percentage
was significantly downregulated in RCs classified as advanced pT
(p= 0.005), angiolymphatic
invasion (p= 0.034), advanced stage (p=0.006), high number of metastatic lymph nodes (p=0.039) and high grade (p=0.014). In univariate
analysis, low EC patients had worse 5-year survival (RFS: 28.3%, p<0.001; OS: 41.2%, p<0.001).
Multivariate analyzes confirmed that low EC is an independent worse survival
parameter for RFS (Hazard ratio [HR]: 1.33
[1.15-3.46], p=0.001) and OS (HR: 1.57
[1.09–4.32], p=0.002).

Conclusions: Our study confirmed the prognostic significance of low EC in stage IV RCs.
Therefore, we suggest that this parameter may be an indicator of worse
prognosis in RCs. This biomarker can be defined on IHC stained
slides readily and can use
a molecular agent in RC therapy.

Keywords: E cadherin, rectal cancer, prognostic markers, stage IV

 

Özet

Amaç: Rektal kanserler (RK) dünya
genelinde en önemli ölüm nedenlerinden biridir. Hastaların sağkalımı temel olarak TNM evresi ile ilişkilidir.
Bununla birlikte, aynı tümör evresi ile karakterize edilen hastalar sıklıkla
belirgin farklı sağ kalımlara sahiptir. Bu özellikle klinik bir çelişkidir ve
yüksek riskli hastaları ayırt etmek için yeni biobelirteçlere ihtiyaç vardır.
Bu araştırmada, stage IV RK'da E cadherin
(EC) 'nin sağ kalımdaki rolünü analiz ettik.

Yöntem:
Bu
retrospektif çalışmaya Kırıkkale Üniversitesi'nde 2001-2015 arasında cerrahi
girişim uygulanan seksen beş RK hastası dahil edildi. EC, immünohistokimyasal
(İHK) boyanmış kesitler üzerinde %50 sınır değeri olarak skorlandı. Sonuçlar ve
klinikopatolojik özellikler arasındaki ilişki analiz edildi.

Bulgular: EC yüzdesi, ileri pT (p = 0.005), anjiyolenfatik invazyon
(p = 0.034), ileri evre (p=0.006), yüksek lenf nodu metastazı sayısı (p=0.039)
ve ileri grade (p=0.014) olan RK'larda anlamlı derecede düşüktü.
Tek değişkenli analizde, düşük EC’li hastalar 5 yıllık kötü sağkalıma sahipti
(RFS:% 28.3, p <0.001; OS:% 41.2, p<0.001). Çok değişkenli analizler,
düşük EC'nin RFS (Hazard
ratio [HR]: 1.33 [1.15 – 3.46], p = 0.001) ve OS (HR: 1.57 [1.09 –
4.32], p=0.002) için bağımsız bir kötü hayatta kalma parametresi olduğunu
doğruladı.

Sonuç:
Sonuçlarımız
stage IV RK'larda düşük EC' nin prognostik önemini doğruladı. Bu nedenle, bu
parametrenin RK'larda kötü prognozun bir göstergesi olabileceğini öneriyoruz.
Bu biyobelirteç, İHK boyalı lamlar üzerinde kolaylıkla tanımlanabilir ve RK
tedavisinde bir moleküler ajan olarak kullanılabilir.

Anahtar
Sözcükler: E cadherin, rektal kanser, prognostik belirteçler, stage
IV

 

Anahtar Kelimeler

E cadherin, rectal cancer, prognostic markers

Kaynakça

• 1. Kulaylat AS, Rivet EB, Hollenbeak CS, Stewart DB. Palliative therapy for stage IV rectal adenocarcinoma: how frequently is it used? J Surg Res. 2017 Oct;218:1-8. 2. Huh JW, Kim HC, Park HC, Choi DH, Park JO, Park YS, et al. Is Chemoradiotherapy Beneficial for Stage IV Rectal Cancer? Oncology. 2015;89(1):14-22.3. Liu R, Li J, Xie K, et al. FGFR4 promotes the stroma-induced epithelial-to-mesenchymal transition in colorectal cancer, Cancer Res. 2013; 73: 5926-59354.Kalluri R, Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119: 1420-1428.5.Yamaguchi H, Wyckoff J, Condeelis J: Cell migration in tumors. Curr Opin Cell Biol 2005; 17: 559-564.6.Valcz G, Sipos F, Krenacs T et al. Increase of alpha-SMA(+) and CK (+) cells as an early sign of epithelial-mesenchymal transition during colorectal carcinogenesis. Pathol Oncol Res 2012; 18: 371-376.7.Sudo T, Iwaya T, Nishida N et al. Expression of mesenchymal markers vimentin and fibronectin: the clinical significance in esophageal squamous cell carcinoma. Ann Surg Oncol 2013; 20: 324-335.8.Saito N, Nishimura H, Kameoka S. Clinical significance of fibronectin expression in colorectal cancer. Mol Med Rep 2008; 1: 77-81.9. Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer 2010; 116(22): 5336–9.10. Dass SD, Cheah PL, Ong DB et al. E-cadherin downregulation at the infiltrating tumor front is associated with histological grade and stage in colorectal carcinoma of Malaysians, Malays J Pathol. 2015; 37(1) :19-24.11. He X, Chen Z, Jia M, Zhao X. Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: evidence from meta-analysis. PLoS One. 2013; 8(7): e70858. 12. Oliphant R, Nicholson GA, Horgan PG et al. Deprivation and colorectal cancer surgery: longer-term survival inequalities are due to differential postoperative mortality between socioeconomic groups, Ann Surg Oncol. 2013; 20: 2132-213913. Kong D, Li Y, Wang Z, Sarkar FH. Cancer stem cells and epithelial-to-mesenchymal transition (EMT)-phenotypic cells: are they cousins or twins? Cancers (Basel) 2011; 3: 716-729.14.Sipos F, Galamb O. Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions in the colon. World J Gastroenterol 2012;18:601-608.15.Polyak K, Weinberg RA: Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9: 265-273.16.Kouso H, Yano T, Maruyama R et al. Differences in the expression of epithelial-mesenchymal transition related molecules between primary tumors and pulmonary metastatic tumors in colorectal cancer. Surg Today 2013; 43: 73-80.17.Zhong YC, Zhang T, Di W, Li WP. Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition. J Gynecol Oncol 2013; 24: 265-272.18.Yang X, Liu S, Yan Q. Role of fucosyltransferase IV in epithelial-mesenchymal transition in breast cancer cells. Cell Death Dis 2013; 4: 735.19. Kim HP, Han SW, Song SH et al. Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer. Oncogene Oncogene. 2014; 33(25): 3334-41.20.Sung CO, Park CK, Kim SH. Classification of epithelial-mesenchymal transition phenotypes in esophageal squamous cell carcinoma is strongly associated with patient prognosis. Mod Pathol 2011; 24: 1060-1068.21. Ye J, Wu D, Shen J, Wu P, Ni C, Chen J et al. Enrichment of colorectal cancer stem cells through epithelial-mesenchymal transition via CDH1 knockdown. Mol Med Report 2012; 6: 507–512.