Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. ⋯ Multivariate analysis demonstrated that both MYC-R and P53 expression were independent prognostic factors in this patient cohort. In conclusion, our data suggest that P53 expression and MYC -R or MYC expression have an additive negative prognostic effect in diffuse large B-cell lymphoma patients. Assessment of P53 expression adds additional prognostic information in de novo diffuse large B-cell lymphoma patients, especially in subgroups with MYC-R, MYC expression and MYC and BCL2 double expression.
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Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key suppressors of the cytotoxic immune response. PD-L1 expression on tumor cells may be induced by the immune microenvironment, resulting in immune escape (adaptive immune resistance), and an adverse prognosis in many malignancies. In colorectal carcinoma the response to PD-1/PD-L1 inhibition is correlated with microsatellite instability. ⋯ PD-L1 positivity was not predictive of survival in the entire cohort, but it was associated with a lower disease-specific survival within the microsatellite-instability high cohort. PD-L1 expression in colorectal carcinoma is associated with clinicopathologic and molecular features of the serrated pathway of colorectal carcinogenesis, and is associated with a worse outcome within microsatellite-unstable tumors. These findings support the role of PD-L1 expression in providing normally immunogenic colorectal carcinoma a means of immune evasion and a more aggressive biology, provide a potential mechanistic explanation for the favorable response of microsatellite-unstable colorectal carcinoma to PD-1/PD-L1 pathway blockade, and suggest potential predictive and prognostic roles of PD-L1 immunohistochemistry in colorectal carcinoma.
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Multicenter Study
Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression.
MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. ⋯ MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression.
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We examined how pathologists' process their perceptions of how their interpretations on diagnoses for breast pathology cases agree with a reference standard. To accomplish this, we created an individualized self-directed continuing medical education program that showed pathologists interpreting breast specimens how their interpretations on a test set compared with a reference diagnosis developed by a consensus panel of experienced breast pathologists. After interpreting a test set of 60 cases, 92 participating pathologists were asked to estimate how their interpretations compared with the standard for benign without atypia, atypia, ductal carcinoma in situ and invasive cancer. ⋯ Nearly 80% (79.8%) reported learning new information from this individualized web-based continuing medical education program, and 23.9% of pathologists identified strategies they would change their practice to improve. In conclusion, when evaluating breast pathology specimens, pathologists do a good job of estimating their diagnostic agreement with a reference standard, but for atypia cases, pathologists tend to overestimate diagnostic agreement. Many participants were able to identify ways to improve.
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Distinction between multiple primary cancers and intrapulmonary metastases in patients with synchronous multifocal lung cancer can be challenging. Histological and genotypic assessment of multifocal lung tumors have been suggested to influence the staging. The aim of this study was to determine the role of morphology and genotype in staging of surgically treated multifocal non-small cell lung carcinoma. ⋯ In addition, squamous cell carcinomas with p16 deletion showed shorter overall survival when compared with squamous cell carcinomas without p16 deletion (P=0.05). No correlation between other molecular alterations, clinico-pathological characteristics and prognosis was found. Our study demonstrates that a comprehensive genotypic and morphological assessment of surgically treated multifocal lung cancers is feasible but not sufficient to establish their clonal relationship and prognosis.