Cribriform-type adenocarcinoma of the colorectum: comprehensive molecular analyses of a distinctive histologic subtype of colorectal cancer.
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ABSTRACT:
SUBMITTER: Yamada S
PROVIDER: S-EPMC9234757 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes. METHODS:The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM. RESULTS:The frequencies of these four subtypes were 69.9% (CA, n?=?15,812), 25.1% (MAC, n?=?5689), 3.6% (SRCC, n?=?814) and 1.4% (AM, n?=?321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC. CONCLUSIONS:We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.
| S-EPMC6842229 | biostudies-literature
Project description:Predicting prognosis is complex due to a unique characteristic in stage IA lung adenocarcinoma. The feature indicated heterogeneous histologic subtype and ground glass opacity (GGO). Many studies demonstrated different prognoses according to histologic subtype or non-GGO lesion. This study aimed to evaluate the clinical outcomes following each histologic subtype size in stage IA lung adenocarcinoma and identify the prognostic impact of each histologic subtype size. The medical records of 550 patients with pathological stage IA lung adenocarcinoma were reviewed. Histologic subtype size was estimated by multiplying the tumor's maximum diameter by the proportion of each histologic subtype. Univariate and multivariate analyses were conducted to identify the prognostic role of each histologic subtype size in stage IA lung adenocarcinoma. The median age and tumor size were 63 [25-82] years and 1.8 [0.3-3] cm, respectively. Acinar (42.0%) and lepidic (44.4%) were the most common among the predominant subtype. Each subtype size was estimated and re-categorized following the current staging system. The disease-free interval (DFI) was significantly different following each histologic subtype size. Multivariate analysis for DFI revealed more acinar, micropapillary, and solid subtypes and fewer lepidic subtypes with worse prognoses. The prognosis for DFI is determined through a complex process by various variables in stage IA lung adenocarcinoma. Each subtype size has a more prognostic impact than the predominant subtype.
| S-EPMC10636469 | biostudies-literature
Project description:To evaluate differences in the clinical characteristics and molecular pathology of lung adenocarcinoma subtypes as defined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international histological classification.We retrospectively reviewed 269 patients with initial primary lung adenocarcinoma who had undergone complete resection at our department from August 2013 to December 2014, focusing on the new histologic subtype classification, clinical characteristics, and molecular pathology.All specimens were invasive adenocarcinoma, and were lepidic (13.0%), papillary (19.7%), acinar (51.7%), solid (8.6%), micropapillary (1.1%) or mucinous predominant (5.9%). Epidermal growth factor receptor (EGFR) mutations were detected in 132 cases (60.3%). Female patients and non-smokers had higher EGFR mutation rates (P = 0.022 and 0.026, respectively). The lepidic, papillary, acinar, solid, micropapillary, and mucinous predominant patterns had EGFR mutation rates of 70.6%, 64.8%, 72.5%, 33.3%, 100%, and 5.9%, respectively. The exon mutation distribution differed according to serum carcinoembryonic antigen (CEA) levels (P = 0.018). v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were detected in 20 cases (9.2%), and were frequently found in the mucinous and solid predominant subtypes. The serum CEA levels differed among the subtypes.In China, there are significant differences between lung adenocarcinoma histologic subtypes. The presence of well-differentiated components in lung adenocarcinoma indicates higher EGFR mutation rates; the presence of solid or mucinous components indicates higher KRAS mutation rates. Serum CEA levels are associated with histologic subtype and EGFR exon mutations.
| S-EPMC4718135 | biostudies-other
Project description:BackgroundLung adenocarcinoma histologic subtype is an important indicator of patient outcomes, so preoperative knowledge of subtype may be helpful to guide surgical planning. We evaluated the sensitivity and prognostic efficacy of specimens from computed tomography-guided core needle biopsies to predict histologic subtype and patient outcome after surgery.MethodsWe retrospectively identified 221 patients with lung adenocarcinoma who underwent computed tomography-guided lung biopsy and subsequent surgical resection. Concordance, accuracy, specificity, and sensitivity of histologic subtypes from core biopsy specimens were compared with surgically resected specimens. Tumor characteristics and biopsy procedural factors were analyzed to determine impact on diagnostic sensitivity. Histologic subtype based on biopsy specimen, clinical, tumor, and treatment variables were also examined in relation to time to progression.ResultsOverall concordance of biopsy samples with the predominant subtype from surgical specimens was 77%. Specificity (sensitivity) of detecting a nonaggressive and aggressive subtype were 86% (93%) and 95% (48%), respectively. Length of core specimen and percentage subtype composition in the surgically resected specimen were correlated with improved sensitivity but to a lesser extent with aggressive subtypes. Presence of an aggressive subtype in biopsy specimens was an independent predictor of progression after surgery (subdistribution hazard ratio, 2.51; 95% confidence interval, 1.28-4.94; p = 0.0075).ConclusionsSpecimens from computed tomography-guided core biopsies can predict lung adenocarcinoma progression after surgical resection. Future prospective studies should address the role of core biopsy in preoperative planning.
| S-EPMC7521186 | biostudies-literature
Project description:BackgroundWe sought to analyze the prognostic significance of the new International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) lung adenocarcinoma (ADC) classification for patients undergoing resection for small (≤2cm) lung ADC and to investigate whether histologic subtyping can predict recurrence after limited resection (LR) vs lobectomy (LO).MethodsComprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification on all consecutive patients who underwent LR or LO for small lung ADC between 1995 and 2009 at Memorial Sloan-Kettering Cancer Center. Clinical characteristics and pathologic data were retrospectively evaluated for 734 consecutive patients (LR: 258; LO: 476). Cumulative incidence of recurrence (CIR) was calculated using competing risks analysis and compared across groups using Grey's test. All statistical tests were two-sided.ResultsApplication of IASLC/ATS/ERS lung ADC histologic subtyping to predict recurrence demonstrates that, in the LR group but not in the LO group, micropapillary (MIP) component of 5% or greater was associated with an increased risk of recurrence, compared with MIP component of less than 5% (LR: 5-year CIR = 34.2%, 95% confidence interval [CI] = 23.5% to 49.7% vs 5-year CIR = 12.4%, 95% CI = 6.9% to 22.1%, P < .001; LO: 5-year CIR = 19.1%, 95% CI = 12.0% to 30.5% vs 15-year CIR = 12.9%, 95% CI = 7.6% to 21.9%, P = .13). In the LR group, among patients with tumors with an MIP component of 5% or greater, most recurrences (63.4%) were locoregional; MIP component of 5% or greater was statistically significantly associated with increased risk of local recurrence when the surgical margin was less than 1cm (5-year CIR = 32.0%, 95% CI = 18.6% to 46.0% for MIP ≥ 5% vs 5-year CIR = 7.6%, 95% CI = 2.3% to 15.6% for MIP < 5%; P = .007) but not when surgical margin was 1cm or greater (5-year CIR = 13.0%, 95% CI = 4.1% to 22.1% for MIP ≥ 5% vs 5-year CIR = 3.4%, 95% CI = 0% to 7.7% for MIP < 5%; P = .10).ConclusionsApplication of the IASLC/ATS/ERS classification identifies the presence of an MIP component of 5% or greater as independently associated with the risk of recurrence in patients treated with LR.
| S-EPMC3748005 | biostudies-literature
Project description:BackgroundOccurrence at a younger age has been demonstrated to be associated with a distinct biology in non-small cell lung cancer. However, genomics and clinical characteristics among younger patients with lung adenocarcinoma remain to be determined. Here we studied the potentially targetable genetic alterations by next-generation sequencing (NGS) assay in young Chinese patients with lung adenocarcinoma.Materials and methodsSeventy-one surgically resected lung adenocarcinoma tissue samples from patients aged less than 45 years were collected with informed consent from all patients. Targeted NGS assays were used to identify actionable genetic alterations in the cancer tissues. Additionally, the genomic and clinicopathologic characteristics of 106 patients with lung adenocarcinoma who received NGS testing over the same period were analyzed retrospectively.ResultsThe frequencies of targetable genetic alterations in 177 patients with lung adenocarcinoma were analyzed by defined age categories, which unveiled a distinctive molecular profile in the younger group, aged less than 45 years. Notably, higher frequency of ALK and HER2 genetic alterations were associated with young age. However, a reverse trend was observed for KRAS, STK11 and EGFR exon 20 mutations, which were more frequently identified in the older group, aged more than 46 years. Furthermore, concurrent EGFR/TP53 mutations were much more prevalent in the younger patients (81.6% vs. 46.8%), which might have a poor response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor.ConclusionIn this study, NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent EGFR/TP53 mutations was found in the younger patients, which especially warranted personalized treatment in this population.Implications for practiceFurther investigation is needed to understand the genomics and clinical characteristics of young patients with lung adenocarcinoma. In the present study, hybrid capture-based next-generation sequencing assays were used to identify targeted genetic alterations in young lung adenocarcinoma patients. Young patients with lung adenocarcinoma, aged less than 45 years, harbored a higher frequency of ALK and HER2 genetic alterations compared with patients aged more than 46 years. Dramatically, concurrent EGFR/TP53 mutations were much more prevalent in younger patients, which had a poor response to treatment with epidermal growth factor receptor kinase inhibitor. These results reveal a distinctive genetic profile in younger patients with adenocarcinoma, which might improve the treatment of this subpopulation.
| S-EPMC6192606 | biostudies-literature
Project description:BackgroundAlthough messenger RNA (mRNA) vaccines have unique advantages against multiple tumors, mRNA vaccine targets in stomach adenocarcinoma (STAD) remain unknown. The potential effectiveness of mRNA vaccines is closely associated with the tumor immune infiltration microenvironment. The present study aimed to identify tumor antigens of STAD as mRNA vaccine targets and systematically determine immune subtypes (ISs) of STAD that might be suitable for immunotherapy.MethodsGene expression profiles and clinical data of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA; n = 409) and the Gene Expression Omnibus (GEO; n = 433), and genomic data were extracted from cBioPortal. Differential gene expression was analyzed using the limma package, genetic alterations were visualized using maftools, and prognosis was analyzed using ToPP. Correlations between gene expression and immune infiltration were calculated using TIMER software, and potential ISs were identified using ConsensusClusterPlus. Functional enrichment was analyzed in clusterProfiler, and r co-expression networks were analyzed using the weighted gene co-expression network analysis (WGCNA) package in R.ResultsOverexpression of the prognostic and highly mutated antigens ADAMTS18, COL10A1, PPEF1, and STRA6 was associated with infiltration by antigen-presenting cells in STAD. Five ISs (IS1-IS5) in STAD with distinct prognoses were developed and validated in TCGA and GEO databases. The tumor mutational burden and molecular and clinical characteristics significantly differed among IS1-IS5. Both IS1 and IS2 were associated with a high mutational burden, massive infiltration by immune cells, especially antigen-presenting cells, and better survival compared with the other subtypes. Both IS4 and IS5 were associated with cold immune infiltration and correlated with advanced pathological stages. We analyzed the immune microenvironments of five subtypes of immune modulators and biomarkers to select suitable populations for mRNA vaccination and established four co-expressed key modules to validate the characteristics of the ISs. Finally, the correlation of these four mRNA vaccine targets with the transcription factors of DC cells, including BATF3, IRF4, IRF8, ZEB2, ID2, KLF4, E2-2, and IKZF1, were explored to reveal the underlying mechanisms.ConclusionsADAMTS18, COL10A1, PPEF1, and STRA6 are potential mRNA vaccine candidates for STAD. Patients with IS1 and IS2 are suitable populations for mRNA vaccination immunotherapy.
| S-EPMC9300892 | biostudies-literature
Project description:Background: DNA methylation (MET)-mediated transcriptomic disturbance and copy number variations (CNVs) exert a significant influence in stimulating the heterogeneous progression of stomach adenocarcinoma (STAD). Nevertheless, the relation of DNA MET with CNVs, together with its impact on tumor occurrence, is still unclear. Methods: The messenger RNA (mRNA) expression (EXP) profiles, DNA MET, and DNA copy numbers, together with STAD mutation data, were collected from the TCGA official data portal. We employed circular binary segmentation algorithm in "DNAcopy." library of R package for mapping DNA CNV data at genetic level for all samples based on the segmented CNV data. Stable clusters of samples were recognized using negative matrix factorization cluster analysis based on 50 iterations and the "brunet" method using the MET-correlated (METcor) and CNV-correlated (CNVcor) genes. The R package "iCluster" method was utilized to comprehensively analyze the EXP, MET, and DNA CNV profiles. Results: A total of 313 STAD samples were isolated for checking DNA copy numbers and MET and for measuring EXP. In accordance with our results, we discovered obvious co-regulation of CNVcor genes and METcor counterparts. Apart from that, these genes were subject to multi-omics integration. Meanwhile, three subtypes of STAD were detected and confirmed based on independent data. Among them, the subtype with increased aggressiveness was related to decreased mutation frequencies of ARID1A, PIK3CA, ZFHX3, SPECC1, OBSCN, KMT2D, FSIP2, ZBTB20, TTN, and RANBP2, together with the abnormal levels of JPH3, KCNB1, and PLCXD3. Conclusion: According to the results, these aforementioned genes exerted crucial roles in the development of invasive STAD. Our findings on transcriptomic regulation genomically and epigenetically facilitate the understanding of the STAD pathology from different aspects, which help to develop efficient anti-STAD therapy.
| S-EPMC8873582 | biostudies-literature
Project description:Whether stromal components facilitate growth, invasion, and dissemination of cancer cells or suppress neoplastic lesions from further malignant progression is a continuing conundrum in tumor biology. Conceptualizing a dynamic picture of tumorigenesis is complicated by inter-individual heterogeneity. In the post genomic era, unraveling such complexity remains a challenge for the cancer biologist. Towards establishing a functional association between cellular crosstalk and differential cancer aggressiveness, we identified a signature of malignant breast epithelial response to stromal signaling. Proximity to fibroblasts resulted in gene transcript alterations of >2-fold for 107 probes, collectively designated as Fibroblast Triggered Gene Expression in Tumor (FTExT). The hazard ratio predicted by the FTExT classifier for distant relapse in patients with intermediate and high grade breast tumors was significant compared to routine clinical variables (dataset 1, n?=?258, HR--2.11, 95% CI 1.17-3.80, p-value 0.01; dataset 2, n?=?171, HR--3.07, 95% CI 1.21-7.83, p-value 0.01). Biofunctions represented by FTExT included inflammatory signaling, free radical scavenging, cell death, and cell proliferation. Unlike genes of the 'proliferation cluster', which are overexpressed in aggressive primary tumors, FTExT genes were uniquely repressed in such cases. As proof of concept for our correlative findings, which link stromal-epithelial crosstalk and tumor behavior, we show a distinctive differential in stromal impact on prognosis-defining functional endpoints of cell cycle progression, and resistance to therapy-induced growth arrest and apoptosis in low vs. high grade cancer cells. Our experimental data thus reveal aspects of 'paracrine cooperativity' that are exclusively contingent upon the histopathologically defined grade of interacting tumor epithelium, and demonstrate that epithelial responsiveness to the tumor microenvironment is a deterministic factor underlying clinical outcome. In this light, early attenuation of epithelial-stromal crosstalk could improve the management of cases prone to be clinically challenging.
| S-EPMC3098270 | biostudies-literature
Project description:To comprehensively compare the survival outcomes of clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC), the study cohort included ccRCC and pRCC patients in 2004-2017 from the Surveillance, Epidemiology, and End Results (SEER) database, which comprises 18 registries. Primary outcomes including overall mortality (OM) and cancer-specific mortality (CSM) were evaluated. Subgroup analyses were conducted for different ages, race, and disease stages. A total of 112,270 cases were eligible for the current analysis, including 92,209 cases of ccRCC and 20,061 cases of pRCC. Univariate analyses suggested that pRCC has a more favorable outcome than ccRCC in terms of CSM (HR: 0.72, 95% CI: 0.68-0.75, p < 0.001) and OM (HR: 0.90, 95% CI: 0.88-0.93, p < 0.001). Multivariate-adjusted HRs suggested that pRCC has worse survival outcomes than ccRCC (adjusted HR: 1.08 for CSM and 1.05 for OM, both p < 0.05). Subgroup analyses showed that pRCC had a significantly poorer prognosis than ccRCC among patients ≤45 years old (HRCSM : 1.59, 95% CI: 1.31-1.93, p < 0.001; HROM : 1.63, 95% CI: 1.40-1.90, p < 0.001). Among patients with distant metastasis, those with pRCC had a higher risk of CSM and OM than those with ccRCC (HRCSM : 1.28, 95% CI: 1.19-1.39, p < 0.001; HROM : 1.30, 95% CI: 1.21-1.40, p < 0.001). Propensity score analyses for patients ≤45 years old and those with metastasis showed similar results. The lack of information on pRCC subtypes in the SEER database was a limitation. In conclusion, pRCC has poorer survival outcomes than ccRCC among patients younger than 45 years old and patients with distant metastasis.
| S-EPMC7774724 | biostudies-literature