Kolorektal kanserli hastalarda tümör taraflılığının önemi ve diğer klinikopatolojik özelliklerle ilişkisi

Yıl 2021, Cilt: 11 Sayı: 2, 275 - 281, 01.08.2021

Nilgun Söğütçü Şahin Laçin Halis Yerlikaya Deniz Yılmaz

Öz

Amaç: Kolorektal kanser (KRK) en yaygın ve ölümcül hastalıklardan biridir ve hastaların sınıflandırılmasında prognostik faktörler çok önemlidir. Bu çalışmada, KRK hastalarında CDX2 ekspresyonu, serum CEA düzeyi ve tümör taraflılığının önemini değerlendirmeyi amaçladık.
Materyal ve Metot: Eylül 2014-Aralık 2019 tarihleri arasında hastalık evresine bakılmaksızın kolorektal kanser tanısı alan hastalar dahil edildi. KRK tanısı primer veya metastatik lezyondan elde edilen patolojik doku bulguları ile doğrulandı. Serum CEA düzeyi, primer tümör taraflılığı (sağ taraf veya sol taraf), CDX2 ekspresyonu ve elde edilen diğer demografik özellikler çalışma değişkeni olarak kaydedildi. Tüm çalışma analizleri SPSS sürüm 22 istatistik yazılımı (IBM Corporation) kullanılarak yapıldı.
Bulgular: KRK'lu 152 hasta dahil edildi, 64 hasta (% 42.1) kadın, 88 hasta (% 57.9) erkek, ortalama yaş 55 (18-93 yaş) idi. Serum CEA düzeyi <3.5ng / ml olan hastalarda ve CEA düzeyi> 3.5 ng / ml olan hastalarda ortalama sağkalım sırasıyla 35.1 ve 26.6 aydı ve gruplar arasındaki fark istatistiksel olarak anlamlıydı (p = 0.006). Hastalık evresi ile serum CEA düzeyi arasında pozitif korelasyon vardı, metastatik hastalarda serum CEA düzeyi metastatik olmayan hastalara göre daha yüksekti (p = 0.009). Doku CDX2 ekspresyonu açısından, on bir hastada (% 7.2) CDX2 ekspresyon negatif, 136 hastada (% 89.5) CDX2 ekspresyon pozitif bulundu. CDX2 ekspresyon durumuna göre hastaların OS oranları arasındaki fark anlamlı değildi (p = 0.7). Sol taraflı hastaların sağ taraflılara göre daha uzun süre hayatta kalmasına rağmen, fark anlamlı değildi, medyan OS sırasıyla 67.6 ve 29.7 aydı (p = 0.3). Ortalama takip süresi 24.1 aydı.
Sonuç: Serum CEA düzeyi, CRC hastaları için belirgin bir prognostik faktör olarak bulundu. Ek olarak CDX2 ekspresyonu pozitif ve sol taraflı primer tümörlerin literatürde bildirildiği gibi daha uzun sağkalımı vardı. Ayrıca, tümör taraflılığı ve serum CEA düzeyine dayanan hasta sınıflama modelimiz umut verici sonuçlar elde etmiştir, ancak daha büyük ve prospektif çalışmalarla doğrulanması gerekmektedir.

Anahtar Kelimeler

CDX2, CEA, kolorektal kanser, serum, tumor gelişim tarafı

The importance of the tumor sidedness and its relationship with other clinicopathological features in patients with colorectal cancer

Öz

Aim: Colorectal cancer (CRC) is one of the most common and mortal diseases and prognostic factors have a crucial role in stratifying patients. We aimed to evaluate the importance of CDX2 expression, serum CEA level, and tumor sidedness in CRC patients.
Material and Method: Patients diagnosed with colorectal cancer between September 2014 and December 2019 were included in the study. Serum CEA level, primary tumor bias, CDX2 expression and other demographic characteristics were recorded as variables. All study analyzes were performed using SPSS version 22 statistical software (IBM Corporation).
Results: 152 patients with CRC were included, 64 (42.1%) of patients were female and 88 (57.9%) of patients were male, the median age of patients was 55(range 18-93). The median survival of patients with serum CEA level < 3.5ng/ml, and the patients with CEA level > 3.5 ng/ml was 35.1 and 26.6 months, respectively, and the difference between groups was a statistically significant (p=0.006). There was a positive correlation between disease stage and serum CEA level, metastatic patients had higher serum CEA level than non-metastatic patients (p=0.009). In terms of tissue CDX2 expression, eleven patients (7.2%) had CDX2 expression negative, 136 (89.5%) of patients had CDX2 expression positive. The difference between OS rates of patients according to CDX2 expression status was not significant (p=0.7). Despite the longer survival of patients with left-sided than right-sided, the difference was not significant, the median OS was 67.6 and 29.7 months, respectively (p=0.3). The median follow-up time was 24.1 months.
Conclusion: The serum CEA level was found as a clear prognostic factor for CRC patients. Additionally, CDX2 expression positive and left-sided primary tumors had longer survival as reported in the literature. Also, our patient stratification model based on tumor sidedness and serum CEA level obtained promising outcomes but need to be confirmed by larger and prospective trials.

Anahtar Kelimeler

CDX2, CEA, colorectal cancer, serum, sidedness

Kaynakça

• 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A:Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA:a cancer journal for clinicians 68:394-424, 2018
• 2. Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al:The 2019 WHO classification of tumours of the digestive system. Histopathology 76:182-188, 2020
• 3. Secco GB, Fardelli R, Campora E, Lapertosa G, Gentile R, Zoli S, et al:Primary mucinous adenocarcinomas and signet-ring cell carcinomas of colon and rectum. Oncology 51:30-4, 1994
• 4. Hyngstrom JR, Hu CY, Xing Y, You YN, Feig BW, Skibber JM, et al:Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma:analysis from the National Cancer Data Base. Ann Surg Oncol 19:2814-21, 2012
• 5. Harrison JC, Dean PJ, el-Zeky F, Vander Zwaag R:From Dukes through Jass:pathological prognostic indicators in rectal cancer. Hum Pathol 25:498-505, 1994
• 6. Berezowski K, Stastny JF, Kornstein MJ:Cytokeratins 7 and 20 and carcinoembryonic antigen in ovarian and colonic carcinoma. Mod Pathol 9:426-9, 1996
• 7. Blumenfeld W, Turi GK, Harrison G, Latuszynski D, Zhang C:Utility of cytokeratin 7 and 20 subset analysis as an aid in the identification of primary site of origin of malignancy in cytologic specimens. Diagn Cytopathol 20:63-6, 1999
• 8. Tot T:Cytokeratins 20 and 7 as biomarkers:usefulness in discriminating primary from metastatic adenocarcinoma. Eur J Cancer 38:758-63, 2002
• 9. Chu P, Wu E, Weiss LM:Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms:a survey of 435 cases. Mod Pathol 13:962-72, 2000
• 10. Dalerba P, Sahoo D, Paik S, Guo X, Yothers G, Song N, et al:CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. N Engl J Med 374:211-22, 2016
• 11. Harrison LE, Guillem JG, Paty P, Cohen AM:Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients:a multivariate analysis of 572 patients. J Am Coll Surg 185:55-9, 1997
• 12. Thirunavukarasu P, Talati C, Munjal S, Attwood K, Edge SB, Francescutti V:Effect of Incorporation of Pretreatment Serum Carcinoembryonic Antigen Levels Into AJCC Staging for Colon Cancer on 5-Year Survival. JAMA Surg 150:747-755, 2015
• 13. Hansen IO, Jess P:Possible better long-term survival in left versus right-sided colon cancer - a systematic review. Dan Med J 59:A4444, 2012
• 14. Richman S, Adlard J:Left and right sided large bowel cancer. BMJ 324:931-2, 2002
• 15. Hamada H, Meno C, Watanabe D, Saijoh Y:Establishment of vertebrate left-right asymmetry. Nat Rev Genet 3:103-13, 2002
• 16. Gervaz P, Bucher P, Morel P:Two colons-two cancers:paradigm shift and clinical implications. J Surg Oncol 88:261-6, 2004
• 17. Olsen J, Espersen ML, Jess P, Kirkeby LT, Troelsen JT:The clinical perspectives of CDX2 expression in colorectal cancer:a qualitative systematic review. Surg Oncol 23:167-76, 2014
• 18. Verzi MP, Shin H, Ho LL, Liu XS, Shivdasani RA:Essential and redundant functions of caudal family proteins in activating adult intestinal genes. Mol Cell Biol 31:2026-39, 2011
• 19. Aasebo K, Dragomir A, Sundstrom M, Mezheyeuski A, Edqvist PH, Eide GE, et al:CDX2:A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup. Front Oncol 10:8, 2020
• 20. Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, et al:Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol 25:1995-2001, 2014
• 21. Moretto R, Cremolini C, Rossini D, Pietrantonio F, Battaglin F, Mennitto A, et al:Location of Primary Tumor and Benefit From Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer. Oncologist 21:988-94, 2016
• 22. Venook AP:Metastatic Colorectal Cancer:Lessons Learned, Future Possibilities. J Natl Compr Canc Netw 14:666-8, 2016
• 23. Lee MS, Menter DG, Kopetz S:Right Versus Left Colon Cancer Biology:Integrating the Consensus Molecular Subtypes. J Natl Compr Canc Netw 15:411-419, 2017
• 24. Meza R, Jeon J, Renehan AG, Luebeck EG:Colorectal cancer incidence trends in the United States and United kingdom:evidence of right- to left-sided biological gradients with implications for screening. Cancer Res 70:5419-29, 2010
• 25. Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousova M, Holubec L, et al:Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers:European group on tumor markers 2014 guidelines update. Int J Cancer 134:2513-22, 2014
• 26. Beauchemin N, Arabzadeh A:Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev 32:643-71, 2013
• 27. Mitsuyama Y, Shiba H, Haruki K, Fujiwara Y, Furukawa K, Iida T, et al:Carcinoembryonic antigen and carbohydrate antigen 19-9 are prognostic predictors of colorectal cancer with unresectable liver metastasis. Oncol Lett 3:767-771, 2012
• 28. Strimpakos AS, Cunningham D, Mikropoulos C, Petkar I, Barbachano Y, Chau I:The impact of carcinoembryonic antigen flare in patients with advanced colorectal cancer receiving first-line chemotherapy. Ann Oncol 21:1013-9, 2010
• 29. Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K, Stanners CP:Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 57:327-34, 1989
• 30. Prager GW, Braemswig KH, Martel A, Unseld M, Heinze G, Brodowicz T, et al:Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer. Cancer Sci 105:996-1001, 2014
• 31. Yoshino T, Obermannova R, Bodoky G, Garcia-Carbonero R, Ciuleanu T, Portnoy DC, et al:Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial. Eur J Cancer 78:61-69, 2017