Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

The Adaptive Immune Landscape of the Colorectal Adenoma-Carcinoma Sequence.

BACKGROUND: The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma-carcinoma sequence (ACS). METHODS: We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). RESULTS: The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. CONCLUSIONS: The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.

Role of Endoscopic Biopsies and Morphologic Features in Predicting Microsatellite Instability Status in Gastric Cancer: A Multicenter Comparative Study of Endoscopic Biopsies and Surgical Specimens.

Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components ( P =0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation ( P <0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases ( P =0.002 and 0.045).

O impacto do ambiente familiar nos primeiros anos de vida: um estudo com adolescentes de uma invasäo de Salvador, Bahia / The impact of early family environment: a study with adolescents from Salvador (Bahia)

Medidas de ajustamento psicossocial de 56 adolescentes de um bairro popular foram efetuadas, mediante um inquérito epidemiológico, para avaliar o poder preditivo de variáveis ambientais e sócio-econômicas, avaliadas quando esses sujeitos tinham entre 0 e 5 anos. Foram consideradas variáveis relativas a três diferentes momentos no curso de vida da família. A qualidade da estimulaçäo no ambiente familiar precoce (escores no inventário HOME) mostrou-se mais importante do que psicopatologia parental na análise de diferenças entre escores médios para problemas (QMPI) e competências (ACQ). O único fator do HOME significativamente correlacionando ao escore no QMPI foi "puniçäo e restriçäo física" (p<0,05). De maneira geral, altos escores no inventário HOME foram associados a mais altos índices de ajustamento. Entretanto, alguns fatores que indicam adversidade nos primeiros anos predisseram níveis mais altos de competência, alertando para a complexidade inerente à determinaçäo de vulnerabilidade ou resiliência no processo do desenvolvimento