Top

Published in:

01-06-2014 | Original Article

Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer

Authors: Valeria Barresi, Giovanni Branca, Antonio Ieni, Luca Reggiani Bonetti, Luigi Baron, Stefania Mondello, Giovanni Tuccari

Published in: Virchows Archiv | Issue 6/2014

Abstract

The practical use of histological factors such as submucosal (SM) invasion depth, poor differentiation, presence of lymphovascular invasion (LVI) and tumour budding to establish the risk of nodal dissemination in pT1 colorectal cancer (CRC) is limited by their low standardization and high inter-observer variability. It was recently suggested that the presence in CRC histological sections of poorly differentiated clusters (PDCs), defined as ≥5 cancer cells with no gland formation, may predict the metastatic potential of CRC. In addition, PDC assessment was shown to be more reproducible than the evaluation of the other aforementioned histological predictors. Hence, in this study, we investigated and compared the predictive value of PDC and other histological parameters on the risk of nodal involvement in pT1 CRC. The presence of PDC, SM invasion depth ≥1,000 μm and LVI was significantly associated with N+ status in pT1 CRC (P < 0.0001). Among these parameters, SM invasion depth had the highest sensitivity to identify N+ pT1 CRC but with the lowest specificity. When the analysis was restricted to CRCs with SM invasion depth ≥1,000 μm, the presence of PDC was the only independent risk factor for nodal metastases and allowed the identification of 87.5 % of N+ cancers. In conclusion, in this study, we demonstrate that the presence of PDC is associated with the metastatic potential of pT1 CRC. The combination of this parameter with SM invasion depth may allow identifying most of the pT1 CRC with nodal metastases.

Hamilton SR, Bosman FT, Boffetta P et al (2010) Carcinoma of the colon and rectum. In: Bosman T, Carneiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system. IARC Press, Lyon, pp 138–139

Kikuchi R, Takano M, Takagi K et al (1995) Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines. Dis Colon Rectum 38:1286–1295PubMedCrossRef

Beaton C, Twine CP, Williams GL et al (2013) Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer. Color Dis 15:788–797CrossRef

Allaix ME, Arezzo A, Caldart M et al (2009) Transanal endoscopic microsurgery for rectal neoplasms: experience of 300 consecutive cases. Dis Colon Rectum 52:1831–1836PubMedCrossRef

Nakadoi K, Tanaka S, Kanao H et al (2012) Management of T1 colorectal carcinoma with special reference to criteria for curative endoscopic resection. J Gastroenterol Hepatol 27:1057–1062PubMedCrossRef

Repici A, Hassan C, Pessoa DDP et al (2012) Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review. Endoscopy 44:137–147PubMedCrossRef

Nakajima T, Saito Y, Tanaka S et al (2013) Current status of endoscopic resection strategy for large, early colorectal neoplasia in Japan. Surg Endosc 27:3262–3270PubMedCrossRef

Tytherleigh MG, Warren BF, Mortensen NJ (2008) Management of early rectal cancer. Br J Surg 95:409–423PubMedCrossRef

Nascimbeni R, Burgart LJ, Nivatvongs S et al (2002) Risk of lymph node metastasis in T1 carcinoma of the colon and rectum. Dis Colon Rectum 45:200–206PubMedCrossRef

10.

Egashira Y, Yoshida T, Hirata I et al (2004) Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancer. Mod Pathol 17:503–511PubMedCrossRef

11.

Tominaga K, Nakanishi Y, Nimura S et al (2005) Predictive histopathologic factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Dis Colon Rectum 48:92–100PubMedCrossRef

12.

Tateishi Y, Nakanishi Y, Taniguchi H et al (2010) Pathological prognostic factors predicting lymph node metastasis in submucosal invasive (T1) colorectal carcinoma. Mod Pathol 23:1068–1072PubMedCrossRef

13.

Kye BH, Jung JH, Kim HJ et al (2012) Tumour budding as a risk factor of lymph node metastasis in submucosal invasive T1 colorectal carcinoma: a retrospective study. BMC Surg 12:16PubMedCentralPubMedCrossRef

14.

Ueno H, Hase K, Hashiguchi Y et al (2013) Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review. J Gastroenterol. doi:10.1007/s00535-013-0881-3

15.

Schmoll HJ, Van Cutsem V, Stein A et al (2012) ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 23:2479–2516PubMedCrossRef

16.

Watanabe T, Itabashi M, Shimada Y et al (2009) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol 17:1–29CrossRef

17.

Quirke P, Risio M, Lambert R et al (2011) Quality assurance in pathology in colorectal cancer screening and diagnosis—European recommendations. Virchows Arch 458:1–19PubMedCentralPubMedCrossRef

18.

Ueno H, Kajiwara Y, Shimazaki H et al (2012) New criteria for histologic grading of colorectal cancer. Am J Surg Pathol 36:193–201PubMedCrossRef

19.

Barresi V, Reggiani Bonetti L, Branca G et al (2012) Colorectal carcinoma grading by quantifying poorly differentiated cell clusters is more reproducible and provides more robust prognostic information than conventional grading. Virchows Arch 461:621–628PubMedCrossRef

20.

Barresi V, Reggiani Bonetti L, Ieni A et al (2013) Histological grading based on the count of poorly differentiated clusters in pre-operative biopsy predicts nodal involvement and pTNM stage in colorectal cancer patients. Hum Pathol 45:268–275PubMedCrossRef

21.

Barresi V, Tuccari G (2013) Colorectal carcinoma grading quantified by counting poorly differentiated clusters: is it feasible on endoscopic biopsies? Am J Surg Pathol 37:943–945PubMedCrossRef

22.

Hamilton SR, Volgelstein B, Kudo S et al (2000) Carcinoma of the colon and rectum. In: Hamilton SR, Aaltonen LA (eds) Pathology and genetics of tumours of the digestive system. IARC Press, Lyon, pp 110–111

23.

Ueno H, Mochizuki H, Hashiguchi Y et al (2004) Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 127:385–394PubMedCrossRef

24.

Barresi V, Reggiani Bonetti L, Vitarelli E et al (2012) Immunohistochemical assessment of lymphovascular invasion in stage I colorectal carcinoma: prognostic relevance and correlation with nodal micrometastases. Am J Surg Pathol 36:66–72PubMedCrossRef

25.

Barresi V, Reggiani-Bonetti L, Di Gregorio C et al (2011) Lymphatic vessel density and its prognostic value in stage I colorectal carcinoma. J Clin Pathol 64:6–12PubMedCrossRef

26.

Chandler I, Houlston RS (2008) Interobserver agreement in grading of colorectal cancers-findings from a nationwide web-based survey of histopathologists. Histopathology 52:494–499PubMedCrossRef

27.

Kudo S (1993) Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy 25:455–461PubMedCrossRef

28.

Lugli A, Karamitopoulou E, Zlobec I (2013) Tumour budding: a promising parameter in colorectal cancer. Br J Cancer 106:1713–1717CrossRef

29.

Mitrovic B, Schaeffer DF, Riddell RH et al (2012) Tumour budding in colorectal carcinoma: time to take notice. Mod Pathol 25:1315–1325PubMedCrossRef

30.

Puppa G, Senore C, Sheahan K et al (2012) Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy. Histopathology 61:562–575PubMed

31.

Choi DH, Sohn DK, Chang HJ et al (2009) Indications for subsequent surgery after endoscopic resection of submucosally invasive colorectal carcinomas: a prospective cohort study. Dis Colon Rectum 52:438–445PubMedCrossRef

32.

Komori K, Hirai T, Kanemitsu Y et al (2010) Is “depth of submucosal invasion ≥1000 micron” an important predictive factor for lymph node metastases in early invasive colorectal cancer (pT1)? Hepatogastroenterology 57:1123–1127PubMed

33.

Reggiani Bonetti L, Di Gregorio C, De Gaetani C et al (2011) Lymph node micrometastasis and survival of patients with stage I (Dukes’ A) colorectal carcinoma. Scand J Gastroenterol 46:881–886PubMedCrossRef

34.

Sakamoto K, Watanabe M, De La Cruz C et al (2005) Primary invasive micropapillary carcinoma of the colon. Histopathology 47:479–484PubMedCrossRef

35.

Ueno H, Hase K, Hashiguchi Y et al (2014) Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters. Am J Surg Pathol 38:197–204PubMedCrossRef

Title: Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer
Authors: Valeria Barresi
Giovanni Branca
Antonio Ieni
Luca Reggiani Bonetti
Luigi Baron
Stefania Mondello
Giovanni Tuccari
Publication date: 01-06-2014
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 6/2014
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-014-1580-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2014

Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics

Coronary cardiac allograft vasculopathy versus native atherosclerosis: difficulties in classification

Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan

Invasive breast carcinomas of no special type with osteoclast-like giant cells frequently have a luminal phenotype

BUB1 mRNA is significantly co-expressed with AURKA and AURKB mRNA in advanced-stage ovarian serous carcinoma

Loss of nuclear prothymosin-α expression is associated with disease progression in human superficial bladder cancer