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Usefulness of Immunohistochemistry for Microsatellite Instability Screening in Gastric Cancer.

Bae YS, Kim H, Noh SH, Kim H - Gut Liver (2015)

Bottom Line: Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses.The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001).Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

Background/aims: The usefulness of immunohistochemistry to screen for the microsatellite instability (MSI) phenotype in gastric cancer remains unclear. Moreover, the prognostic value of MSI phenotypes in gastric cancer has been debated.

Methods: The clinicopathologic parameters and survival outcomes of 203 MSI-high (MSI-H) and 261 microsatellite-stable (MSS) advanced gastric cancers (AGCs) were compared. Next, we compared the immunohistochemistry results for hMLH1 and hMSH2 with those of a polymerase chain reaction (PCR)-based method. Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses.

Results: The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001). Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001). Compared with the PCR-based analysis, immunohistochemistry exhibited high sensitivity (91.1%) and specificity (98.5%) in the detection of MSI phenotypes.

Conclusions: MSI-H gastric cancers have distinct clinicopathologic features and better prognoses, which suggests the necessity of MSI analysis in gastric cancer. Immunohistochemistry can be a useful and reliable screening method in the assessment of MSI status in gastric cancer.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves according to hMLH1 and hMSH2 expressions. The loss of hMLH1 expression was significantly associated with a survival benefit (A), whereas the loss of hMSH2 expression was associated with a tendency toward a better prognosis that did not reach statistical significance (B).
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f3-gnl-09-629: Kaplan-Meier survival curves according to hMLH1 and hMSH2 expressions. The loss of hMLH1 expression was significantly associated with a survival benefit (A), whereas the loss of hMSH2 expression was associated with a tendency toward a better prognosis that did not reach statistical significance (B).

Mentions: The results of univariate and multivariate survival analyses are summarized in Table 2. Upon univariate analysis, MSS phenotype (p<0.001), larger tumor size (>6 cm, p<0.001), Borrmann’s type III/IV (p<0.001), poorly differentiated histology (p=0.011), diffuse type by Lauren’s classification (p<0.001), deeper depth of invasion (pT4, p<0.001), presence of lymph node metastasis (p<0.001), presence of metastasis (p<0.001), and presence of lymphovascular invasion (p<0.001) were correlated with poor survival outcomes. The multivariate analyses using those significant variables showed that the MSS phenotype was an independent risk factor for worse survival outcomes (hazard ratio, 1.798; 95% confidence interval, 1.095 to 2.935; p=0.020). In terms of other parameters, tumor size (p=0.005), Borrmann’s type (p=0.041), lymphovascular invasion (p=0.004), depth of invasion (p=0.002), lymph node metastasis (p=0.001), and distant metastasis (p=0.001) were correlated with patient survival. The survival benefit in MSI-H GCs was also demonstrated by Kaplan-Meier survival curves (Fig. 2A). Even when grouped according to stage, these tumors showed a better prognosis, particularly stage II (p=0.003) (Fig. 2B). Stage III tumors, although not statistically significant, were found to have a tendency towards better overall survival (p=0.116) (Fig. 2C). Statistical significance was achieved when the intestinal type cases were selectively included (p=0.010) (Fig. 2D). Furthermore, the survival benefit of MSI-H GCs was additionally analyzed by separating cases into an hMLH1 loss group and an hMSH2 loss group. Loss of hMLH1 expression was significantly associated with a better prognosis (p<0.001 on univariate analysis and p=0.03 on multivariate analysis), while loss of hMSH2 expression tended to show survival benefit without statistical power (Supplementary Table 1, Fig. 3).


Usefulness of Immunohistochemistry for Microsatellite Instability Screening in Gastric Cancer.

Bae YS, Kim H, Noh SH, Kim H - Gut Liver (2015)

Kaplan-Meier survival curves according to hMLH1 and hMSH2 expressions. The loss of hMLH1 expression was significantly associated with a survival benefit (A), whereas the loss of hMSH2 expression was associated with a tendency toward a better prognosis that did not reach statistical significance (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562780&req=5

f3-gnl-09-629: Kaplan-Meier survival curves according to hMLH1 and hMSH2 expressions. The loss of hMLH1 expression was significantly associated with a survival benefit (A), whereas the loss of hMSH2 expression was associated with a tendency toward a better prognosis that did not reach statistical significance (B).
Mentions: The results of univariate and multivariate survival analyses are summarized in Table 2. Upon univariate analysis, MSS phenotype (p<0.001), larger tumor size (>6 cm, p<0.001), Borrmann’s type III/IV (p<0.001), poorly differentiated histology (p=0.011), diffuse type by Lauren’s classification (p<0.001), deeper depth of invasion (pT4, p<0.001), presence of lymph node metastasis (p<0.001), presence of metastasis (p<0.001), and presence of lymphovascular invasion (p<0.001) were correlated with poor survival outcomes. The multivariate analyses using those significant variables showed that the MSS phenotype was an independent risk factor for worse survival outcomes (hazard ratio, 1.798; 95% confidence interval, 1.095 to 2.935; p=0.020). In terms of other parameters, tumor size (p=0.005), Borrmann’s type (p=0.041), lymphovascular invasion (p=0.004), depth of invasion (p=0.002), lymph node metastasis (p=0.001), and distant metastasis (p=0.001) were correlated with patient survival. The survival benefit in MSI-H GCs was also demonstrated by Kaplan-Meier survival curves (Fig. 2A). Even when grouped according to stage, these tumors showed a better prognosis, particularly stage II (p=0.003) (Fig. 2B). Stage III tumors, although not statistically significant, were found to have a tendency towards better overall survival (p=0.116) (Fig. 2C). Statistical significance was achieved when the intestinal type cases were selectively included (p=0.010) (Fig. 2D). Furthermore, the survival benefit of MSI-H GCs was additionally analyzed by separating cases into an hMLH1 loss group and an hMSH2 loss group. Loss of hMLH1 expression was significantly associated with a better prognosis (p<0.001 on univariate analysis and p=0.03 on multivariate analysis), while loss of hMSH2 expression tended to show survival benefit without statistical power (Supplementary Table 1, Fig. 3).

Bottom Line: Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses.The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001).Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

Background/aims: The usefulness of immunohistochemistry to screen for the microsatellite instability (MSI) phenotype in gastric cancer remains unclear. Moreover, the prognostic value of MSI phenotypes in gastric cancer has been debated.

Methods: The clinicopathologic parameters and survival outcomes of 203 MSI-high (MSI-H) and 261 microsatellite-stable (MSS) advanced gastric cancers (AGCs) were compared. Next, we compared the immunohistochemistry results for hMLH1 and hMSH2 with those of a polymerase chain reaction (PCR)-based method. Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses.

Results: The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001). Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001). Compared with the PCR-based analysis, immunohistochemistry exhibited high sensitivity (91.1%) and specificity (98.5%) in the detection of MSI phenotypes.

Conclusions: MSI-H gastric cancers have distinct clinicopathologic features and better prognoses, which suggests the necessity of MSI analysis in gastric cancer. Immunohistochemistry can be a useful and reliable screening method in the assessment of MSI status in gastric cancer.

No MeSH data available.


Related in: MedlinePlus