Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome

Journal of Experimental & Clinical Cancer Research

Marcello Anti³  Isabella Sperduti²  Beatrice Casini⁴  Maria Diodoro⁴  Aline Martayan¹  Lupe Sanchez-Mete³  Vittoria Stigliano³ 

[1] Division of Clinical Pathology, Regina Elena National Cancer Institute, IFO Via Elio Chianesi 53, 00144 Rome, Italy;Division of Biostatistics, Regina Elena National Cancer Institute, IFO Via Elio Chianesi 53, 00144 Rome, Italy;Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, IFO Via Elio Chianesi 53, 00144 Rome, Italy;Division of Pathology, Regina Elena National Cancer Institute, IFO Via Elio Chianesi 53, 00144 Rome, Italy

关键词: Microsatellite instability;    Immunohistochemistry;    Lynch syndrome;    Early-onset colorectal cancer;   

Others  :  813912
DOI  :  10.1186/1756-9966-33-1

 received in 2013-10-17, accepted in 2013-12-08,  发布年份 2014

【 摘 要 】

Introduction

Several studies evaluated the prevalence of Lynch Syndrome (LS) in young onset colorectal cancer (CRC) patients and the results were extremely variable (5%-20%). Immunohistochemistry (IHC) for MMR proteins and/or MSI analysis are screening tests that are done, either by themselves or in conjunction, on colon cancer tissue to identify individuals at risk for LS. The primary aim of our study was to evaluate the prevalence of LS in a large series of early-onset CRC without family history compared with those with family history. The secondary aim was to assess the diagnostic accuracy of IHC and MSI analysis as pre-screening tools for LS.

Methods

Early-onset CRC patients (≤ 50 years) were prospectively recruited in the study. IHC and MSI analysis were performed in all the patients. Germ-line mutation analysis (GMA) was carried out in all MMR deficient tumors. A logistic regression model was performed to identify clinical features predictive of MSI-H.

Results

117 early onset CRC cases were categorized in three groups (A, B, C) according with family history of CRC. IHC and MSI analysis showed MMR deficiency in 6/70 patients (8.6%) of group A, 24/40 patients (60%) of group B and none of group C. GMA showed a deleterious mutation in 19 (47.5%) patients of group B. MSI analysis had a diagnostic accuracy of 95.7% (CI 92.1-99.4) and IHC of 83.8% (CI 77.1-90.4). The logistic regression model revealed that by using a combination of the two features “No Amsterdam Criteria” and ”left sided CRC” to exclude MSI-H, accuracy was 89.7% (84.2-95.2).

Conclusions

Early-onset CRC patients, with left sided CRC and without family history are “at very low risk” for Lynch syndrome. The two simple criteria of family history and CRC site could be used as a pre-screening tool to evaluate whether or not patients should undergo tissue molecular screening. In the few cases of suspected LS (right sided CRC and/or Amsterdam Criteria), a reasonable approach could be to perform MSI analysis first and IHC afterwards only in MSI-H patients.

【 授权许可】

   
2014 Stigliano et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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