Microsatellite instability of the colorectal carcinoma can be predicted in the conventional pathologic examination. A prospective multicentric study and the statistical analysis of 615 cases consolidate our previously proposed logistic regression model.
High microsatellite instability (MSI-H) allows the identification of a subset of colorectal carcinomas associated with good prognosis and a higher incidence of Lynch syndrome. The aim of this work was to assess the interobserver variability and optimize our MSI-H prediction model previously published based on phenotypic features.The validation series collected from five different hospitals included 265 primary colorectal carcinomas from the same number of patients. The eight clinicopathological parameters that integrate our original model were evaluated in the corresponding centers. Homogeneity assessment revealed significant differences between hospitals in the estimation of the growth pattern, presence of Crohn-like reaction, percentage of cribriform structures, and Ki-67 positivity. Despite this observation, our model was globally able to predict MSI-H with a negative predictive value of 97.0%. The optimization studies were carried out with 615 cases and resulted in a new prediction model RERtest8, which includes the presence of tumor infiltrating lymphocytes at the expense of the percentage of cribriform structures. This refined model achieves a negative predictive value of 97.9% that is maintained even when the immunohistochemical parameters are left out, RERtest6. The high negative predictive value achieved by our models allows the reduction of the cases to be tested for MSI to less than 10%. Furthermore, the easy evaluation of the parameters included in the model renders it a useful tool for the routine practice and can reinforce other published models and the current clinical protocols to detect the subset of colorectal cancer patients bearing hereditary nonpolyposis colorectal cancers risk and/or MSI-H phenotype.
Román
Ruth
R
BIOPAT. Biopatologia Molecular, SL, Grup Assistència, Avda. Diagonal 660, Barcelona, Spain. rroman@biopat.es
Verdú
Montse
M
Calvo
Miquel
M
Vidal
August
A
Sanjuan
Xavier
X
Jimeno
Mireya
M
Salas
Antonio
A
Autonell
Josefina
J
Trias
Isabel
I
González
Marta
M
García
Beatriz
B
Rodón
Natalia
N
Puig
Xavier
X
D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
Mod Pathol. 2006 Jan;19(1):59-68
16118624
Am J Pathol. 1998 Oct;153(4):1063-78
9777938
Science. 1993 May 7;260(5109):816-9
8484122
Mod Pathol. 2004 Jun;17(6):696-700
15017435
Int J Cancer. 2003 Aug 10;106(1):66-73
12794758
Fam Cancer. 2004;3(2):93-100
15340259
Gastroenterology. 2007 Jul;133(1):48-56
17631130
Cell. 1990 Jun 1;61(5):759-67
2188735
J Mol Diagn. 2008 Jan;10(1):13-27
18165277
N Engl J Med. 2003 Jul 17;349(3):247-57
12867608
Gut. 2001 Mar;48(3):360-6
11171826
Cancer Res. 1998 Nov 15;58(22):5248-57
9823339
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5
9618505
Genes Chromosomes Cancer. 1992 Jul;5(1):89-90
1384667
Gut. 1998 May;42(5):673-9
9659163
Am J Surg Pathol. 2009 Jan;33(1):126-33
18830122
Diagn Mol Pathol. 2005 Dec;14(4):213-23
16319691
N Engl J Med. 1994 Jul 28;331(4):213-21
8015568
N Engl J Med. 2000 Jan 13;342(2):69-77
10631274