Study of histopathologic parameters to define the prognosis of stage II colon cancer
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Stage II colon cancer (CC) represents a challenging scenario for the choice of adjuvant chemotherapy; here, histologic factors need to be weighed up to establish the risk of recurrence. Tumor budding (TB) has recently been indicated as a confident predictor of clinical outcome in CC. Likewise, the presence of poorly differentiated clusters (PDCs) in a tumor has been pointed out as a leading criterion of a tumor grading system. Our aim was to evaluate in patients with stage II CC the relationship between these features and clinical outcome.
Patients and methods
The study included 174 cases of stage II CC; histopathologic parameters such as TB, PDCs, microsatellite instability (MSI), and CDX2 expression were analyzed.
There were 107 (70.9%), 32 (21.2%), and 12 (7.9%) TB scored 1, 2, and 3 respectively; 113 (72.9%), 30 (19.4%), and 12 (7.7%) tumors showed grade 1, 2, and 3 PDCs respectively. A high-MSI was detected in 32 cases (18.4%) while CDX2 was negative in 20 (11.5%) tumor samples. In the whole study population, only the TB was found to be associated with disease-specific survival (P = 0.01). No parameter apart from age (P = 0.04) was a significant prognostic factor for overall survival (P < 0.05). Other commonly reported variables, including tumor size, degree of tumor differentiation, lymphovascular invasion, number of lymph nodes harvested ≥ 12, MSI, and PDCs, were not shown to have significant results.
Although confirmatory studies are awaited, our work supports the role of the TB in defining risk groups of the stage II CC.
KeywordsColon cancer Stage II Tumor budding Poorly differentiated cluster CDX2 Microsatellite instability
We wished to thank Dr. Laura Di Fede and Dr. Denise Quacquarini for technical assistance with immunohistochemistry and molecular analysis.
Compliance with ethical standards
The study was conducted in accordance with the Declaration of Helsinki and the protocol approved by the institutional (Sapienza University) ethical committee (N.3874_2015/22.10.2015).
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Benson AB, Robert CH, Venook AP, Cederquist L, Chan E, V.-I. Cancer Center Yi-Jen Chen, H.S. Cooper, A. Fichera, J.L. Grem, P. Buffett Cancer Center, A. Grothey, H.S. Hochster, S. Hunt, A. Kamel, S. Krishnamurthi, M.F. Mulcahy, J.D. Murphy, S. Nurkin, L. Saltz, D. Shibata, J.M. Skibber, C.T. Sofocleous, E.M. Stoffel, E. Stotsky-Himelfarb, C.G. Willett, C.S. Wu, N. Deborah Freedman-Cass, K.M. Gregory (2017) NCCN Guidelines Version 2.2017 Panel Members Colon Cancer MD/Vice-Chair UCSF Helen Diller Family Comprehensive Cancer CenterGoogle Scholar
- 4.Hutchins G, Southward K, Handley K, Magill L, Beaumont C, Stahlschmidt J, Richman S, Chambers P, Seymour M, Kerr D, Gray R, Quirke P (2011) Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 29(10):1261–1270CrossRefGoogle Scholar
- 10.Bertagnolli MM, Redston M, Compton CC, Niedzwiecki D, Mayer RJ, Goldberg RM, Colacchio TA, Saltz LB, Warren RS (2011) Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer—a study of CALGB 9581 and 89803. J Clin Oncol 29(23):3153–3162CrossRefGoogle Scholar
- 11.Romiti A, Rulli E, Pilozzi E, Gerardi C, Roberto M, Legramandi L, Falcone R, Pacchetti I, Marchetti P, Floriani I (2016) Exploring the prognostic role of microsatellite instability in patients with stage II colorectal cancer: a systematic review and meta-analysis. Clin Colorectal CancerGoogle Scholar
- 12.Dalerba P, Sahoo D, Paik S, Guo X, Yothers G, Song N, Wilcox-Fogel N, Forgó E, Rajendran PS, Miranda SP, Hisamori S, Hutchison J, Kalisky T, Qian D, Wolmark N, Fisher GA, van de Rijn M, Clarke MF (2016) CDX2 as a prognostic biomarker in stage II and stage III colon cancer. N Engl J Med 374(3):211–222CrossRefGoogle Scholar
- 14.Tomasello G, Barni, S, Turati L, Ghidini M, Pezzica E, Passalacqua R, Petrelli F (2018) Association of CDX2 expression with survival in early colorectal cancer: a systematic review and meta-analysisGoogle Scholar
- 15.Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, El Zimaity H, Fléjou JF, Hansen TP, Hartmann A, Kakar S, Langner C, Nagtegaal I, Puppa G, Riddell R, Ristimäki A, Sheahan K, Smyrk T, Sugihara K, Terris B, Ueno H, Vieth M, Zlobec I, Quirke P (2017) Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol 30:1299–1311CrossRefGoogle Scholar
- 17.Kinoshita O, Kishimoto M, Murayama Y, Yasukawa S, Konishi E, Otsuji E, Yanagisawa A (2015) Poorly differentiated clusters with larger extents have a greater impact on survival: a semi-quantitative pathological evaluation for 239 patients with non-mucinous pT2-3 colorectal carcinoma. World J Surg Oncol 13:140CrossRefGoogle Scholar
- 20.Punt CJA, Buyse M, Kohne C-H, Hohenberger P, Labianca R, Schmoll HJ, Pahlman L, Sobrero A, Douillard J-Y (2007) Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. JNCI J Natl Cancer Inst 99(13):998–1003CrossRefGoogle Scholar
- 21.Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, Beaumont C, Clark-Langone KM, Yoshizawa CN, Lee M, Watson D, Shak S, Kerr DJ (2011) Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol 29(35):4611–4619CrossRefGoogle Scholar
- 24.Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, Hamilton SR, Hammond ME, Henson DE, Hutter RV, Nagle RB, Nielsen ML, Sargent DJ, Taylor CR, Welton M, Willett C (2000) Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 124(7):979–994Google Scholar
- 30.Ueno H, Konishi T, Ishikawa Y, Shimazaki H, Ueno M, Aosasa S, Saiura A, Hase K, Yamamoto J (2014) Histologic categorization of fibrotic cancer stroma in the primary tumor is an independent prognostic index in resectable colorectal liver metastasis. Am J Surg Pathol 38(10):1380–1386CrossRefGoogle Scholar
- 31.van Wyk HC, Park J, Roxburgh C, Horgan P, Foulis A, McMillan DC (2015) The role of tumour budding in predicting survival in patients with primary operable colorectal cancer: a systematic reviewGoogle Scholar
- 34.Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349(3):247–257CrossRefGoogle Scholar
- 35.Sinicrope FA, Foster NR, Thibodeau SN, Marsoni S, Monges G, Labianca R, Yothers G, Allegra C, Moore MJ, Gallinger S, Sargent DJ (2011) DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst 103(11):863–875CrossRefGoogle Scholar
- 36.Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, French AJ, Kabat B, Foster NR, Torri V, Ribic C, Grothey A, Moore M, Zaniboni A, Seitz J-F, Sinicrope F, Gallinger S (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28(20):3219–3226CrossRefGoogle Scholar