Purpose
The aim of this study was to elucidate the rates and prognostic roles of programmed cell death ligand 1 (PD-L1) immunohistochemical (IHC) expression in various malignant tumors through a ...systematic review and meta-analysis.
Method
The current study included 16,176 patients from 97 eligible studies. We investigated PD-L1 expression and its correlation with survival rate in various malignant tumors.
Results
The estimated rate of PD-L1 IHC expression was 0.449 (95% confidence interval CI 0.404-0.495). The highest and lowest PD-L1 expression levels were found in thyroid cancer (0.829, 95% CI 0.781-0.868) and small-cell neuroendocrine carcinoma (0.005, 95% CI 0.000-0.080), respectively. PD-L1 expression was significantly correlated with poorer overall survival and disease-free survival rates (hazard ratios 1.276, 95% CI 1.097-1.486 and 1.304, 95% CI 1.034-1.644, respectively). However, PD-L1 IHC expression was significantly correlated with worse overall survival rates in patients with esophageal cancer and renal cell carcinoma and with worse disease-free survival rates in patients with colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma.
Conclusions
Our results show that PD-L1 expression rates and the correlations with survival varied between tumor types. Detailed evaluation criteria for PD-L1 will have to be standardized before application to specific tumor types.
Summary Medullary carcinoma (MC) is a very rare variant of colorectal carcinoma (CRC). Its clinicopathologic findings are not fully elucidated. The aim of this study was to investigate the ...clinicopathological characteristics of MC in the colorectum through a systematic review and meta-analysis. The meta-analysis examined the incidence, age, sex, site, mismatch repair deficiency (MMRd), MMR protein expression, ARID1A expression, BRAFV600E mutation, KRAS mutation, and survival rate of MC. The 21,469 CRCs included 462 MCs in 16 eligible studies, representing an estimated incidence of MC of 0.027 95% confidence interval (CI) 0.016-0.045. MC frequently occurred in female patients and in the right colon. Lymph node metastasis of MC was significantly lower than that of poorly differentiated adenocarcinoma/undifferentiated adenocarcinoma (PDA/UDA). In addition, MC had a higher MMRd rate (0.892, 95% CI 0.758-0.956), higher BRAFV600E mutation rate (0.652, 95% CI 0.143-0.954) and lower KRAS mutation rate (0.171, 95% CI 0.065-0.378) than PDA/UDA and conventional adenocarcinoma. Patients with MC had significantly better overall survival rate compared to patients with PDA/UDA (hazard ratio 0.441, 95% CI 0.262-0.742). However, there was no significant difference of overall survival rate between MC and conventional adenocarcinoma patients. MC predominantly occurred in females and in the right colon, and had different molecular characteristics and behaviors compared to PDA/UDA and conventional adenocarcinoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
About 10-15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional ...mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies.
We performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations.
We identified 24 GIST lacking alterations in the canonical KIT/PDGFRA/RAS pathways, including 12 without SDHx alterations. These 24 patients were mostly adults (96%). The tumors had a 46% rate of nodal metastases. These 24 GIST were more commonly mutated at 7 genes: ARID1B, ATR, FGFR1, LTK, SUFU, PARK2 and ZNF217. Two tumors harbored FGFR1 gene fusions (FGFR1-HOOK3, FGFR1-TACC1) and one harbored an ETV6-NTRK3 fusion that responded to TRK inhibition. In an independent sample set, we identified 5 GIST cases lacking alterations in the KIT/PDGFRA/SDHx/RAS pathways, including two additional cases with FGFR1-TACC1 and ETV6-NTRK3 fusions.
Using patient demographics, tumor characteristics, and CGP, we show that GIST lacking alterations in canonical genes occur in younger patients, frequently metastasize to lymph nodes, and most contain deleterious genomic alterations, including gene fusions involving FGFR1 and NTRK3. If confirmed in larger series, routine testing for these translocations may be indicated for this subset of GIST. Moreover, these findings can be used to guide personalized treatments for patients with GIST. Trial registration NCT 02576431. Registered October 12, 2015.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this study was to elucidate the diagnostic and prognostic roles of the mean platelet volume (MPV) in various malignant tumors through a systematic review and meta-analysis. The current ...study included 2,053 patients and 1,396 healthy subjects in 18 eligible studies. We performed a meta-analysis of MPV levels and the mean difference between healthy subjects and pre- and post-treatment patients. Subgroup analysis was conducted based on specific organs and platelet counts. In addition, the correlation between MPV and survival was investigated. The pooled MPVs of healthy subjects, pre-treatment, and post-treatment patients were 8.428 fL (95% confidence interval CI 8.118-8.738), 8.831 fL (95% CI 8.582-9.087), and 8.521 fL (95% CI 8.162-8.880), respectively. The mean difference in MPV between healthy subjects and pre-treatment patients was 0.502 (95% CI 0.285-0.719, P < 0.001). However, in lung cancer, the mean difference between pre-treatment patients and healthy subjects was −0.352 (95% CI −0.763-0.060, P = 0.094). The pooled MPV of post-treatment patients was significantly decreased compared to pre-treatment patients. There was no correlation between MPV and disease-free survival rate (hazard ratio 1.033, 95% CI 0.369-2.895). Our results showed that the MPV level was significantly higher in malignant tumors than in healthy subjects and was decreased after treatment. Further cumulative studies will be required before MPV levels can be applied for screening malignant tumors and predicting prognosis.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The present study aimed to evaluate the clinicopathological significance and prognostic implications of REG4 immunohistochemical expression in colorectal cancer (CRC).
We performed ...immunohistochemical analysis for REG4 cytoplasmic expression in 266 human CRC tissues. Correlations between REG4 expression, clinicopathological characteristics, and survival were investigated in CRC.
REG4 was expressed in 84 of 266 CRC tissues (31.6%). REG4 expression was significantly more frequent in the right colon than that in the left colon and rectum (
= 0.002). However, we observed no significant correlation between REG4 expression and other clinicopathological parameters. REG4 expression was significantly higher in CRCs with low stroma than in those with high stroma (
= 0.006). In addition, REG4 was more frequently expressed in CRCs with the mucinous component than in those without it (
< 0.001). There was no significant correlation between REG4 expression and overall recurrence-free survival (
= 0.132 and
= 0.480, respectively). Patients with REG4 expression showed worse overall and recurrence-free survival in the high-stroma subgroup (
= 0.001 and
= 0.017, respectively), but no such correlation was seen in the low stroma subgroup (
= 0.232 and
= 0.575, respectively).
REG4 expression was significantly correlated with tumor location, amount of stroma, and mucinous component in CRCs. In patients with high stroma, REG4 expression was significantly correlated with poor overall and recurrence-free survival.
Purpose
The aim of this study was to investigate the prognostic relevance of the Ki-67 labeling index (LI) in gastrointestinal stromal tumor (GIST) through a systematic review, meta-analysis and ...diagnostic test accuracy review.
Method
The study included 1,967 GIST cases from 24 eligible studies. We investigated the correlation between high Ki-67 LI and survival and the proper criteria for high Ki-67 LI. In addition, a diagnostic test accuracy review was conducted to evaluate the predictive role of high Ki-67 LI for higher risk of tumor recurrence.
Results
A high Ki-67 LI was significantly correlated with worse disease-free survival (DFS) (hazard ratio HR 3.658, 95% confidence interval CI 2.687-4.979, p<0.001) and overall survival (OS) (HR 3.730, 95% CI 2.819-4.936, p<0.001). With regard to DFS and OS, the subgroup with a cutoff value of >4% for high Ki-67 LI had a higher HR than the subgroup with a ≤4% cutoff. In the diagnostic test accuracy review, a high Ki-67 LI was significantly correlated with higher risk of tumor recurrence (pooled sensitivity = 0.44, pooled specificity = 0.87, area under the curve on the summary receiver operating characteristic curve = 0.656).
Conclusions
Our results showed that a high Ki-67 LI was significantly correlated with worse prognosis and higher risk of tumor recurrence in GIST. Further prospective studies of the prognostic role of Ki-67 LI are necessary prior to application in clinical practice.
Purpose:
The aim of this study was to investigate the rate of ROS1 rearrangement and concordance between ROS1 immunohistochemistry (IHC) and molecular tests in non-small cell lung cancer (NSCLC).
...Methods:
The study included 10,898 NSCLC cases from 21 eligible studies. ROS1 rearrangement rates were evaluated in NSCLC by a meta-analysis, including subgroup analyses. In addition, we performed a concordance analysis and a diagnostic test accuracy review of ROS1 IHC in NSCLC.
Results:
The estimated overall rate of ROS1 rearrangement and IHC positivity was 2.4% (95% confidence interval (CI) 1.5, 3.7). In the subgroup analysis, which was based on tumor subtype, the rate of ROS1 rearrangement and IHC positivity was 2.9% (95% CI 1.9, 4.5) and 0.6% (95% CI 0.3, 1.2) in adenocarcinoma and non-adenocarcinoma, respectively. The overall concordance rate between ROS1 IHC and molecular tests was 93.4% (95% CI 78.3, 98.2). In ROS1 IHC positive and negative cases, the concordance rates were 79.0% (95% CI 43.3, 94.9) and 97.0% (95% CI 83.3, 99.5), respectively. The pooled sensitivity and the specificity of ROS1 IHC were 0.90 (95% CI 0.70, 0.99) and 0.82 (95% CI 0.79, 0.84), respectively. The diagnostic odds ratio and the area under the curve of the summary receiver operating characteristic curve were 118.01 (95% CI 11.81, 1179.67) and 0.9417, respectively.
Conclusion:
The rates of ROS1 rearrangement differed by tumor histologic subtype in NSCLC. ROS1 IHC may be useful for the detection of ROS1 rearrangement in NSCLC. Detailed criteria for evaluating ROS1 IHC are needed before it can be applied in daily practice.
Background: This study aims to evaluate the clinicopathological significance and prognostic implications of intratumoral budding (ITB) in colorectal cancers (CRCs) through a meta-analysis. Methods: ...We performed the meta-analysis using 13 eligible studies and investigated the rates of CRCs with high ITB. The correlation between ITB and clinicopathological characteristics, including disease-free survival, was evaluated. Results: The estimated rate of CRCs with high ITB was 0.233 (95% confidence interval (CI) 0.177–0.299) in overall CRCs. High ITB was significantly correlated with tumor grade, lymphatic invasion, perineural invasion, pT stage, and lymph node metastasis. In addition, ITBs were more frequently found in medullary and signet-ring cell carcinomas than in conventional adenocarcinomas and mucinous carcinomas. However, the high ITB rate was not correlated with tumor border, tumor-infiltrating lymphocytes, or microsatellite instability. CRCs with a good response after neoadjuvant therapy revealed a lower rate of high ITB than those with a poor response (hazard ratio (HR) 0.114, 95% CI 0.070–0.179 vs. 0.321, 95% CI 0.204–0.467). In addition, CRCs with high ITB had a worse disease-free survival than those with low ITB (HR 1.426, 95% CI 1.092–1.863). Conclusions: The ITB was significantly correlated with aggressive tumor behaviors and a worse prognosis in CRCs. The detection of ITB, as a histological parameter, can be useful for predicting clinicopathologic features and the prognosis of CRC.
The present study aimed to elucidate the clinicopathological significance and prognostic implications of tumor-stroma ratio (TSR) in colorectal cancers (CRCs). TSRs were investigated in 266 human CRC ...specimens. The correlations between TSR and clinicopathological characteristics and survival were evaluated. The hypoxia-inducible factor-1α (HIF-1α) immunohistochemical expression of tumor cells and microvessel density (MVD) of stroma were compared between stroma-low and stroma-high subgroups. Results: Stroma-low was found in 185 of 266 CRCs (69.5%). Stroma-low was significantly correlated with less frequent vascular and perineural invasion and distant metastasis than stroma-high. HIF-1α of tumor cells was more highly expressed in the stroma-high subgroup than in the stroma-low subgroup. In addition, MVD was significantly higher in the stroma-high subgroup compared to the stroma-low subgroup. The stroma-low rate was increased considerably in CRCs with a mucinous component and decreased in CRCs with a micropapillary component. There were significant correlations between stroma-low and better overall and recurrence-free survivals. Similar to the literature, we observed that stroma-low was significantly correlated with favorable tumor behaviors and better survival. The microscopic examination of TSR can be useful for predicting the prognosis of CRC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
As storage temperature impacts frozen meat quality, we evaluated the ideal freezing and storage temperatures for pork loin, and effects of long-term storage at − 60, − 50, and − 18 °C on pork loin ...physicochemical properties. Pork loin was cut into 30 × 30 × 30 mm (50 g) and packed in air-containing box. Thereafter, they were stored at different freezing temperature for 6 months. Frozen pork loins were thawed at 4 °C. Samples frozen at − 18 °C exhibited surface dehydration (at 3 months) and high moisture loss surface dehydration-induced discoloration and toughening. However, samples frozen by deep freezing temperature (− 60 and − 50 °C) had lower values of thawing loss, WHC, and shear force than those of frozen at − 18 °C. Samples frozen at − 60 and − 50 °C maintained their freshness better than those frozen at − 18 °C; samples stored at − 60 °C showed significantly lower VBN than those stored at − 50 °C. Therefore, − 60 °C is suitable for freezing pork loins.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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