ORIGINAL ARTICLE
Poorly differentiated clusters: prognostic significance in colorectal carcinomas
 
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1
Department of Pathology, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania
 
2
Department of Pathology, Emergency County Hospital “Pius Brînzeu” Timisoara, Romania
 
3
Department of Surgery II, “Victor Babeş” University of Medicine and Pharmacy, Timisoara, Romania
 
4
Department of Surgery II, Emergency County Hospital “Pius Brînzeu” Timisoara, Romania
 
 
Submission date: 2019-02-26
 
 
Final revision date: 2019-06-19
 
 
Acceptance date: 2019-07-30
 
 
Publication date: 2020-03-06
 
 
Pol J Pathol 2019;70(4):235-245
 
KEYWORDS
TOPICS
ABSTRACT
Colorectal cancer (CRC) remains a major public health burden worldwide, despite increased knowledge on its pathogenesis and advances in therapy. We aimed to evaluate a new histological grading system based on poorly differentiated clusters (PDCs) counting – the PDCs grade (PDCs-G), and its clinicopathological and prognostic significance, compared to the World Health Organisation (WHO) grading system (WHO grade).
We reviewed 71 surgical resection specimens for CRC from the Emergency County Hospital “Pius Brînzeu” Timisoara. The cases were graded using the WHO grade and the PDCs-G, with further analysis of their association with the other recognised prognostic parameters.
Using the WHO grade, 9% of the analysed cases were G1, 80% G2, 11% G3, and none of the tumours was graded G4, while in the PDCs-G 16% were G1, 45% G2, and 39% G3. In multivariate analysis PDCs-G was significantly associated with the American Joint Committee on Cancer stage of the disease (AJCC stage) (p = 0.0003), depth of invasion (pT) (p = 0.0084), nodal status (LNM) (p < 0.0001), lymphovascular invasion (LVI) (p < 0.0001), perineural invasion (PNI) (p < 0.0052), and tumour border configuration (p < 0.0001).
The novel grading system based on PDCs counting is an additional histological tool in the evaluation of CRC and a promising new prognostic factor for these patients.
REFERENCES (53)
1.
Fitzmaurice C, Allen C, Barber RM, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study Global Burden. JAMA Oncol 2017; 3: 524-548.
 
2.
Arnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66: 683-691.
 
3.
Brierley JD, Gospodarowicz MK, Wittekind C, et al. Digestive System Tumors. Colon and Rectum. TNM Classification of Malignant Tumors. Wiley Blackwell (8th ed.). Oxford, UK 2017; 73-77.
 
4.
Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. 8th ed. Springer, New York 2017; 252-254.
 
5.
Loughrey M, Quirke P, Shepherd N, et al. Standards and datasets for reporting cancers Dataset for histopathological reporting of colorectal cancer. The Royal College of Pathologists, London 2018; G049: 19-20.
 
6.
Hamilton SR, Bosman FT, Boffetta P, et al. Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, Theise ND (eds.). WHO Classification of Tumors of the Digestive System (4th ed.). IARC Press, Lyon 2010; 137-138.
 
7.
Ueno H, Hase K, Hashiguchi Y, et al. Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review. J Gastroenterol 2014; 49: 1314-1323.
 
8.
Ueno H, Hashiguchi Y, Kajiwara Y, et al. Proposed objective criteria for ‘grade 3’ in early invasive colorectal cancer. Am.
 
9.
J Clin Pathol 2010; 134: 312-322.
 
10.
Barresi V, Bonetti LR, Ieni A, et al. Histological grading in colorectal cancer: new insights and perspectives. Histol Histopathol 2015; 30: 1059-1067.
 
11.
RCPA (Royal College of Pathologists of Australasia) Colorectal Cancer Structured Reporting Protocol (3rd ed.). RCPA, Surry Hills, NSW 2016; 23-31.
 
12.
Barresi V, Reggiani Bonetti L, Branca G, et al. Colorectal carcinoma grading by quantifying poorly differentiated cell clusters is more reproducible and provides more robust prognostic information than conventional grading. Virchows Arch 2012; 461: 621-628.
 
13.
Reggiani Bonetti L, Lionti S, Domati F, et al. Histological grading based on poorly differentiated clusters is predictive of tumor response and clinical outcome in rectal carcinoma treated with neoadjuvant chemoradiotherapy. Histopathology 2017; 71: 393-405.
 
14.
Chandler I, Houlston RS. Interobserver agreement in grading of colorectal cancers-findings from a nationwide web-based survey of histopathologists. Histopathology 2008; 52: 494-499.
 
15.
Jass JR, O’Brien MJ, Riddell RH, et al. Recommendations for the reporting of surgically resected specimens of colorectal carcinoma. Virchows Arch 2007; 450: 1-13.
 
16.
Ueno H, Kajiwara Y, Shimazaki H, et al. New criteria for histologic grading of colorectal cancer. Am J Surg Pathol 2012; 36: 193-201.
 
17.
Ueno H, Hase K, Hashiguchi Y, et al. Site-specific tumor grading system in colorectal cancer: Multicenter pathologic review of the value of quantifying poorly differentiated clusters. Am.
 
18.
J Surg Pathol 2014; 38: 197-204.
 
19.
Reggiani Bonetti L, Barresi V, Bettelli S, et al. Poorly differentiated clusters (PDC) in colorectal cancer: What is and ought to be known. Diagn Pathol 2016; 22: 11-31.
 
20.
Barresi V, Reggiani Bonetti L, Ieni A, et al. Poorly differentiated clusters: clinical impact in colorectal cancer. Clin Colorectal Cancer 2017; 16: 9-15.
 
21.
Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 2007; 50: 113-130.
 
22.
Sagaert X. Prognostic biomarkers in colorectal cancer: Where do we stand? Virchows Archiv 2014; 464: 379-391.
 
23.
Morson B, Dawson I, Spriggs A, Jones F. Gastrointestinal pathology. 2nd ed. Oxford, Blackwell Scientific Publications 1979; 551-610.
 
24.
Morson B, Sobin L. Histological typing of intestinal tumors. Geneva, World Health Organization 1976; 13-38.
 
25.
Shepherd NA, Saraga EP, Love SB, et al. Prognostic factors in colonic cancer. Histopathology 1989; 14: 613-620.
 
26.
Hamilton SR, Vogelstein B, Kudo S, et al. Carcinoma of the colon and rectum. In: Hamilton SR, Aaltonen LA (eds.). Pathology and Genetics of Tumors of the Digestive System. IARC. Lyon, France 2000; 105-119.
 
27.
College of American Pathologists (CAP). Protocol for Examination of Specimens From Patients With Primary Carcinoma of the Colon and Rectum. Version: ColoRectum 4.0.1.0. CAP 2017; 12-16.
 
28.
Kuijpers CJ, Sluijter CE, Von der Thüsen JH, et al. Interlaboratory variability in the histologic grading of colorectal adenocarcinomas in a nationwide cohort. Am J Surg Pathol 2016; 40: 1100-1108.
 
29.
Zlobec I, Lugli A. Prognostic and predictive factors in colorectal cancer. Postgrad Med J 2008; 8: 403-411.
 
30.
Kim JW, Shin MK, Kim BC. Clinicopathologic impacts of poorly differentiated cluster-based grading system in colorectal carcinoma. J Korean Med Sci 2015; 30: 16-23.
 
31.
Dema A, Taban S, Jurescu A, et al. Paving the way to tumor budding assessment using digital pathology: a pilot study in Timisoara City (Romania). Rom J Morphol Embryol 2018; 59: 703-715.
 
32.
Lugli A, Kirsch R, Ajioka Y, et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol 2017; 30: 1299-1311.
 
33.
Zlobec I, Lugli A. Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget 2010; 1: 651-661.
 
34.
Ueno H, Shinto E, Kajiwara Y, et al. Prognostic impact of histological categorization of epithelial-mesenchymal transition in colorectal cancer. Br J Cancer 2014; 111: 2082-2090.
 
35.
Compton CC, Fielding LP, Burgart LJ, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000; 124: 979-994.
 
36.
Karamitopoulou E, Zlobec I, Kölzer V, et al. Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer. Mod Pathol 2013; 26: 295-301.
 
37.
Satoh K, Nimura S, Aoki M, et al. Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c-Met. Cancer Sci 2014; 105: 1487-1495.
 
38.
Kai K, Aishima S, Aoki S, et al. Cytokeratin immunohistochemistry improves interobserver variability between unskilled pathologists in the evaluation of tumor budding in T1 colorectal cancer. Pathol Int 2016; 66: 75-82.
 
39.
Barresi V, Branca G, Ieni A, et al. Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer. Virchows Arch 2014; 464: 655-662.
 
40.
Kinoshita O, Kishimoto M, Murayama Y, et al. The number of metastatic lymph nodes exhibiting poorly differentiated clusters predicts survival in patients with pStage III colorectal cancer. Int J Colorectal Dis 2016; 31: 283-290.
 
41.
Song BR, Xiao CC, Wu ZK. Predictors of lymph node metastasis and prognosis in pT1 colorectal cancer patients with signet-ring cell and mucinous adenocarcinomas. Cell Physiol Biochem 2017; 41: 1753-1765.
 
42.
Barresi V, Bonetti LR, Ieni A, et al. Histologic grading based on counting poorly differentiated clusters in preoperative biopsy predicts nodal involvement and pTNM stage in colorectal cancer patients. Hum Pathol 2014; 45: 268-275.
 
43.
Barresi V, Tuccari G. Colorectal carcinoma grading quantified by counting poorly differentiated clusters: is it feasible on endoscopic biopsies? Am J Surg Pathol 2013; 37: 943-945.
 
44.
Park JS, Huh JW, Park YA, et al. Prognostic comparison between mucinous and nonmucinous adenocarcinoma in colorectal cancer. Medicine (Baltimore) 2015; 94: e658.
 
45.
Kinoshita O, Kishimoto M, Murayama Y, et al. 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 2015; 13: 140.
 
46.
Marzouk O, Schofield J. Review of histopathological and molecular prognostic features in colorectal cancer. Cancers (Basel) 2011; 3: 2767-2810.
 
47.
Barresi V, Reggiani Bonetti L, Ieni A, et al. Prognostic significance of grading based on the counting of poorly differentiated clusters in colorectal mucinous adenocarcinoma. Hum Pathol 2015; 46: 1722-1729.
 
48.
Barresi V, Reggiani Bonetti L, Ieni A, et al. Histologic prognostic markers in stage IIA colorectal cancer: a comparative study. Scand J Gastroenterol 2016; 51: 314-320.
 
49.
Yang M, Rehman AU, Zuo C, et al. A novel histologic grading scheme based on poorly differentiated clusters is applicable to treated rectal cancer and is associated with established histopathological prognosticators. Cancer Med 2016; 5: 1510-1518.
 
50.
Maguire A, Sheahan K. Controversies in the pathological assessment of colorectal cancer. World J Gastroenterol 2014; 20: 9850-9861.
 
51.
Hong M, Kim JW, Shin MK, et al. Poorly Differentiated clusters in colorectal adenocarcinomas share biological similarities with micropapillary patterns as well as tumor buds. J Korean Med Sci 2017; 32: 1595-1602.
 
52.
Zhang S, Zhang D, Yang Z, et al. Tumor budding, micropapillary pattern, and polyploidy giant cancer cells in colorectal cancer: current status and future prospects. Stem Cells Int 2016; 2016: 4810734.
 
53.
Barresi V, Branca G, Vitarelli E, et al. Micropapillary pattern and poorly differentiated clusters represent the same biological phenomenon in colorectal cancer: a proposal for a change in terminology. Am J Clin Pathol 2014; 142: 375-383.
 
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