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

Abstract

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.

Microsatellite instability in colorectal cancer: from molecular oncogenic mechanisms to clinical implications

“…MSI tumours tend to share various clinicopathologic characteristics including preferential location in the proximal colon, poor differentiation with a mucinous aspect, a Crohn-like inflammatory reaction and an excess of infiltrating lymphocytes within the tumour that have been used to refine the screening of MSI tumours among familial [74,87] and/ or sporadic cases [68,159]. Guidelines to detect Lynch syndrome or MSI tumours keep changing as our knowledge improves and should not be seen as definitely established, but evidence accumulates showing that it is time to diagnose MSI tumours in the general population [185].…”

Prospective validation of the microsatellite instability prediction models: RERtest6 and RERtest8

“…17,18 Briefly, such features included: tumor location, proximal or distal to the splenic flexure (including rectum), growth pattern, expansive or infiltrative, presence of peritumoral Crohn-like lymphoid reactivity (which was considered positive when at least three nodular aggregates of lymphocytes were present within a single low (4×) power field), percentage of solid and mucinous differentiation and presence of tumor-infiltrating lymphocytes (TIL) characterized by the finding of at least four intraepithelial lymphocytes in a high-power field (40×) (Fig. 1).…”

“…13---16 The purpose of this study was to validate further, with a prospective series, two previously published logistic models for the prediction of MSI-H, RERtest6 and RERtest8, based on clinicopathological features and developed as a result of the optimization of an initial model with a multicentric validation. 17,18 …”

Lynch or Not Lynch? Is that Always a Question?

“…histopathology: several histological features are more commonly seen in MSI CRCs compared to MSS tumors, including poor differentiation, mucinous phenotype, lack of "dirty" necrosis, increased number of tumor intraepithelial lymphocytes, circumscribed/expansive growth pattern, and a prominent inflammatory reaction at the edge of the tumor (so-called Crohn's like reaction). These phenotypic particularities have been used to create various morphological scores aimed at discriminating MSI and MSS tumors (Greenson et al, 2009;Hyde et al, 2010;Jenkins et al, 2007;Roman et al, 2010). The scores generally have a high negative predictive value to diagnose MSI, but only a moderate to low positive predictive value.…”