Top

Published in:

01-11-2011 | Colorectal Cancer

Early-Onset Colorectal Cancer is an Easy and Effective Tool to Identify Retrospectively Lynch Syndrome

Authors: José Perea, MD, PhD, Yolanda Rodríguez, MD, Daniel Rueda, PhD, José C. Marín, MD, José Díaz-Tasende, MD, Edurne Álvaro, MD, Cristina Alegre, MD, Irene Osorio, MD, Francisco Colina, MD, PhD, Manuel Lomas, MD, PhD, Manuel Hidalgo, MD, PhD, Javier Benítez, PhD, Miguel Urioste, MD, PhD

Published in: Annals of Surgical Oncology | Issue 12/2011

Abstract

Background and Objectives

Early age of onset is a marker of a possible hereditary component in colorectal cancer (CRC). We evaluated whether early age of onset is a good marker to identify Lynch syndrome, especially retrospectively, and if there is any other feature that could improve this identification.

Methods

We selected patients with CRC aged 45 years or younger from the pathological reports of three different institutions and different periods of time. Clinical information, family history, and tumor samples were obtained. Cases were classified according to mismatch repair (MMR) proficiency.

Results

Of 133 tumors, 22 showed microsatellite instability (MSI). In 15 MSI cases, a germline mutation in 1 of the MMR genes was identified, 7 of which were not identified before. The positive predictive value (PPV) of right colon CRC for a positive genetic MMR test is 30.6%, whereas “signet ring” cells and fulfillment Amsterdam II criteria have PPVs of 42.9% and 47.8%, respectively. Combining right-sided CRC with mucin production, with fulfilling Amsterdam II criteria, or with “signet ring” cells, PPVs are 54.5, 64.3, and 100%. The probability of the absence of a mutation when CRC is located in the left colon is 94.7%, whereas absence of aggregation for Lynch-related neoplasm has a 100% probability.

Conclusions

Early age of onset is an effective method to identify retrospectively Lynch syndrome. Taking into account the location and histology features of the tumor, and the familial history of the cases, we notably increase the a priori probability of detecting a germline MMR mutation.

Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005;16:481–8.

Siegel RL, Jemal A, Ward EM. Increase in incidence of colorectal cancer among young men and women in the United States. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1695–8.PubMedCrossRef

Aaltonen LA, Salovaara R, Kristo P, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med. 1998;338:1481–7.PubMedCrossRef

Samowitz WS, Curtin K, Lin HH, et al. The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer. Gastroenterology. 2001;121:830–8.PubMedCrossRef

Watson P, Lynch HT. The tumor spectrum in HNPCC. Anticancer Res. 1994;14:1635–9.PubMed

Vasen HF, Watson P, Mecklin JP, et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116:1453–6.PubMedCrossRef

Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34:424–5.PubMedCrossRef

Rodriguez-Bigas MA, Boland CR, Hamilton SR, et al. A National Cancer Institute Workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst. 1997;89:1758–62.PubMedCrossRef

Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda guidelines for hereditary non polyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261–8.PubMedCrossRef

10.

Liang JT, Huang KC, Cheng AL, et al. Clinicopathological and molecular biological features of colorectal cancer in patients less than 40 years of age. Br J Surg. 2003;90:205–14.PubMedCrossRef

11.

Losi L, Di Gregorio C, Pedroni M, et al. Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes. Am J Gastroenterol. 2005;100:2280–7.PubMedCrossRef

12.

Yiu R, Qiu H, Lee SH, et al. Mechanisms of microsatellite instability in colorectal cancer patients in different age groups. Dis Colon Rectum. 2005;48:2061–9.PubMedCrossRef

13.

Perea J, Alvaro E, Rodriguez Y, et al. Approach to early-onset colorectal cancer: Clinicopathological, familial, molecular and immunohistochemical characteristics. World J Gastroenterol. 2010;16:3697–703.PubMedCrossRef

14.

Aaltonen LA, Peltomaki P, Mecklin JP, et al. Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res. 1994;54:1645–8.PubMed

15.

Farrington SM, Lin-Goerke J, Ling J, et al. Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls. Am J Hum Genet. 1998;63:749–59.PubMedCrossRef

16.

Chiang JM, Chen MC, Changchien CR, et al. Favorable influence of age on tumor characteristics of sporadic colorectal adenocarcinoma. Dis Colon Rectum. 2003;46:904–10.PubMedCrossRef

17.

Gryfe R, Kim H, Hsieh ET, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342:69–77.PubMedCrossRef

18.

Chung YFA, Eu KW, Machin D, et al. Young age is not a poor prognostic marker in colorectal cancer. Br J Surg. 1998;85:1255–9.PubMedCrossRef

19.

Foo W, Young JM, Solomon MJ, Wright CM. Family history? The forgotten question in high-risk colorectal cancer patients. Colorectal Dis. 2009;11:450–5.PubMedCrossRef

20.

Overbeek LIH, Hoogerbrugge N, van Krieken J, et al. Most patients with colorectal tumors at young age do not visit a Cancer Genetic Clinic. Dis Colon Rectum. 2008;51:1249–54.PubMedCrossRef

21.

Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.PubMed

22.

Rouleau E, Lefol C, Bourdon V, et al. Quantitative PCR High-Resolution Melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome. Hum Mutat. 2009;30:867–75.PubMedCrossRef

23.

Kloor M, Voigt AY, Schackert HK, et al. Analysis of EPCAM protein expression in diagnostics of Lynch syndrome. J Clin Oncol. 2011;29:223–7.PubMedCrossRef

24.

Southey MC, Jenkins MA, Mead L, et al. Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer. J Clin Oncol. 2005;23:6524–32.PubMedCrossRef

25.

Niessen RC, Berends MJW, Wu Y, et al. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours with hereditary non-polyposis colorectal cancer. Gut. 2006;55:1781–8.PubMedCrossRef

26.

Pucciarelli S, Agostini M, Viel A, et al. Early-age-at-onset colorectal cancer and microsatellite instability as markers of hereditary nonpolyposis colorectal cancer. Dis Colon Rectum 2003;46:305–12.PubMedCrossRef

27.

Perea J, Ortiz M, Hidalgo M, et al. Importance of family history in colorectal cancer clinical practice. Colorectal Dis. 2010;12:606.PubMedCrossRef

Title: Early-Onset Colorectal Cancer is an Easy and Effective Tool to Identify Retrospectively Lynch Syndrome
Authors: José Perea, MD, PhD
Yolanda Rodríguez, MD
Daniel Rueda, PhD
José C. Marín, MD
José Díaz-Tasende, MD
Edurne Álvaro, MD
Cristina Alegre, MD
Irene Osorio, MD
Francisco Colina, MD, PhD
Manuel Lomas, MD, PhD
Manuel Hidalgo, MD, PhD
Javier Benítez, PhD
Miguel Urioste, MD, PhD
Publication date: 01-11-2011
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 12/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-1782-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Early-Onset Colorectal Cancer is an Easy and Effective Tool to Identify Retrospectively Lynch Syndrome

Abstract

Background and Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2011

Selective Organ Preservation in Operable Locally Advanced Head and Neck Squamous Cell Carcinomas Guided by Primary Site Restaging Biopsy: Long-Term Results of Two Sequential Brown University Oncology Group Chemoradiotherapy Studies

Mechanisms of Improved Outcomes for Breast Cancer between Surgical Oncologists and General Surgeons

Primum non nocere: A Word of Caution Regarding Prophylactic Colectomy in the Setting of Incurable Metastatic Disease

Molecular Imaging of Proliferation and Glucose Utilization: Utility for Monitoring Response and Prognosis after Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Prognostic Significance of Stromal Microinvasion in the Intestinal Type of Ovarian Mucinous Adenocarcinoma

Normal PTH Levels in Primary Hyperparathyroidism: Still the Same Disease?