Thématique :
- Cancers autres (hors CCR et CHC)
Originalité :
Solidité :
Très solide
Doit faire évoluer notre pratique :
Nom du veilleur :
Professeur Sylvain MANFREDI
Coup de coeur :
Journal of the National Cancer Institute (JNCI)
  2018 Sep ;110(9):975-984.  
  doi: 10.1093/jnci/djy004.  
  The Heterogeneity Between Lynch-Associated and Sporadic MMR Deficiency in Colorectal Cancers  
  Liu GC, Liu RY, Yan JP, An X, Jiang W, Ling YH, Chen JW, Bei JX, Zuo XY, Cai MY, Liu ZX, Zuo ZX, Liu JH, Pan ZZ, Ding PR  



Previous studies demonstrated that prognosis of germline deficiency in mismatch repair protein (dMMR) was different from that of sporadic dMMR. The underlying mechanism has not been studied.


From a prospectively maintained database, we collected dMMR colorectal cancer (CRC) patients identified by postoperative immunohistochemistry screening. According to genetic test, patients were grouped as Lynch-associated or sporadic dMMR. We compared the clinical-pathological features, prognosis, and immunoreactive differences between the two groups. By whole-exome sequencing and neoantigen detection pipeline, mutational frequencies and neoantigen burdens were also compared. All statistical tests were two-sided.


Sixty-seven sporadic dMMR and 85 Lynch-associated CRC patients were included in the study. Sporadic dMMR patients were older (P < .001) and their tumors were poorly differentiated (P = .03). The survival was better in the Lynch-associated group (P = .001). After adjustment, the difference still remained statistically significant (hazard ratio = 0.29, 95% confidence interval = 0.09 to 0.95, P = .04). The scores of Crohn's-like reaction (CRO; P < .001), immunoreactions in the invasive margin (IM; P = .01), tumor stroma (TS; P = .009), and cancer nest (CN; P = .02) of the Lynch-associated group were statistically significantly higher. The numbers of CD3+, CD8+, Foxp3+ tumor-infiltrating lymphocytes (TILs) in IM; CD3+, CD4+ TILs in TS; and CD3+, CD4+, CD8+ TILs in CN were statistically significantly higher in Lynch-associated dMMR patients. Based on the 16 patients who under went whole-exome sequencing, there were also more somatic mutations and neoantigen burdens in the Lynch-associated group compared with the sporadic dMMR group (439/pt vs 68/pt, P = .006; 628/pt vs 97/pt, P = .009).


There are heterogeneities in dMMR CRCs. Lynch-associated dMMR patients present with more somatic mutations and neoantigens compared with sporadic dMMR, which probably results in stronger immunoreactions and survival improvement.

Question posée
Différences entre les cancers coliques MSI sporadiques et Lynch ?
Question posée
Différences nettes : les sporadiques sont plus âgés, plus souvent indifférenciés. Les Lynch ont plus de mutations somatiques associées et sont plus immunogènes. Les MSI Lynch ont un meilleur pronostic que les MSI sporadiques.