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Molecular & Cellular Proteomics : MCP May 2024The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological,...
Proteomics-Derived Biomarker Panel Facilitates Distinguishing Primary Lung Adenocarcinomas With Intestinal or Mucinous Differentiation From Lung Metastatic Colorectal Cancer.
The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical (IHC), and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging-based shotgun proteomics to characterize proteomes of formalin-fixed, paraffin-embedded tumor samples of PAIM (n = 22) and lmCRC (n = 17).Then three machine learning algorithms, namely support vector machine (SVM), random forest, and the Least Absolute Shrinkage and Selection Operator, were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by IHC to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection. The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of ten candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: CK7 (an established marker), NARR, MLPH, S100A14) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.
Topics: Humans; Biomarkers, Tumor; Proteomics; Lung Neoplasms; Colorectal Neoplasms; Adenocarcinoma of Lung; Male; Female; Diagnosis, Differential; Cell Differentiation; Middle Aged; Aged; Adenocarcinoma
PubMed: 38608841
DOI: 10.1016/j.mcpro.2024.100766 -
European Journal of Radiology Jun 2024To assess the diagnostic value of abbreviated protocol (AP) MRI to detect the degeneration signs in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) in...
PURPOSE
To assess the diagnostic value of abbreviated protocol (AP) MRI to detect the degeneration signs in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) in patients undergoing a routine MRI follow-up.
METHODS
This dual-center retrospective study include patients with BD-IPMN diagnosed on initial comprehensive protocol (CP) MRI who underwent routine MRI follow-up. CP included axial and coronal T2-weighted images (T2WI), axial T1-weighted images (T1WI) before and after contrast administration, 3D MR cholangiopancreatography (MRCP) and diffusion-weighted images (DWI). Two APs, eliminating dynamic sequences ± DWI, were extracted from CP. Two radiologists evaluated the APs separately for IPMN degeneration signs according to Fukuoka criteria and compared the results to the follow-up CP. In patients who underwent EUS, imaging findings were correlated with pathological results. Per-patient and per-lesion sensitivity, specificity, PPV, NPV, and accuracy of APs were calculated. Additionally, the acquisition time for different protocols was calculated.
RESULTS
One hundred-fourteen patients (56.1 % women, median age: 71 years) with 256 lesions were included. Degeneration signs were observed in 24.6 % and 12.1 % per-patient and per-lesion, respectively. Regarding APs, the per patient sensitivity, specificity, PPV, NPV, and accuracy in the detection of the degeneration signs were 100 %, 93.5 %, 83.3 %, 100 %, and 95.1 %, respectively. No additional role for DWI was detected. AP without DWI economized nearly half of CP acquisition time (388 versus 663 s, respectively).
CONCLUSION
AP can confidently replace CP for BD-IPMN follow-up with high sensitivity and PPV while offering benefits such as patient comfort, improved MRI accessibility, and reduced dedicated time for image analysis. DWI necessitates special consideration.
CLINICAL RELEVANCE STATEMENT
Our data suggest that APs safely detect all degeneration signs of IPMN. While there is an overestimation of mural nodules due to the lack of contrast injection, this occurs in a negligible number of patients.
Topics: Humans; Female; Male; Aged; Retrospective Studies; Sensitivity and Specificity; Pancreatic Neoplasms; Middle Aged; Magnetic Resonance Imaging; Aged, 80 and over; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous; Contrast Media; Pancreatic Intraductal Neoplasms; Cholangiopancreatography, Magnetic Resonance; Reproducibility of Results; Diffusion Magnetic Resonance Imaging
PubMed: 38608499
DOI: 10.1016/j.ejrad.2024.111455 -
Annals of Surgical Oncology Jul 2024Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may...
BACKGROUND
Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed.
PATIENTS AND METHODS
Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling.
RESULTS
Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22].
CONCLUSIONS
Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.
Topics: Humans; Appendiceal Neoplasms; Female; SEER Program; Male; Adenocarcinoma, Mucinous; Middle Aged; Colectomy; Aged; Survival Rate; Appendectomy; Adenocarcinoma; Follow-Up Studies; Prognosis; Neoplasm Recurrence, Local; Neoplasm Staging; Adult
PubMed: 38594579
DOI: 10.1245/s10434-024-15233-9 -
Cureus Apr 2024Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts...
Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts the frequency of MSI in sporadic CRCs and its effect on prognosis. This study investigated the distribution of clinicopathologic features and the relationship between MSI and survival outcomes. Methodology This is a retrospective study of 101 consecutive cases of CRC and immunohistochemical studies. All cases were retrospectively reviewed and reevaluated by histological grade, lymphovascular invasion, perineural invasion, tumor borders, dirty necrosis, tumor-infiltrating lymphocytes (TILs), Crohn's-like lymphoid reaction, mucinous and medullary differentiation, and tumoral budding from pathological slides. An immunohistochemical study was performed in appropriate blocks for using MLH-1, MSH-2, MSH-6, and PMS-2. We collected the clinical stage, pathological tumor stage, lymph node metastasis, age, sex, tumor diameter, distant metastasis, localization, and survival information from patients' clinical data. Results There was no statistically significant difference between the two groups regarding age, gender, tumor diameter, histological grade, tumor border, dirty necrosis, TILs, N and M stage, perineural and lymphovascular invasion, mucinous differentiation, medullary differentiation, and tumor budding characteristics of the patients. The MSI-H group was more frequently located in the right colon and transverse colon (p < 0.001), and the T stage was higher among them than in the MSI-L group (p = 0.014). Upon multivariate regression analysis, MSI status had no significant effect on survival time. Age and stage N and M were independent prognostic factors for colon cancer prognosis. Conclusions Our study presented the distribution of clinicopathological features and their relationship with MSI for 101 regional CRC patients. MSI status was detected by immunohistochemistry. Identifying MSI in CRCs may help personalize therapy planning. As the distribution of the features may vary from population to population, further investigations are needed on this topic.
PubMed: 38590982
DOI: 10.7759/cureus.57814 -
Medicine Apr 2024The selection of appropriate treatment modalities based on the presence or absence of mutations in KRAS, NRAS, BRAF, and the microsatellite instability (MSI) status has...
The selection of appropriate treatment modalities based on the presence or absence of mutations in KRAS, NRAS, BRAF, and the microsatellite instability (MSI) status has become a crucial consensus in colorectal cancer (CRC) therapy. However, the distribution pattern of these genetic mutations and the prevalence of MSI status in Chinese stage I-III CRCs remain unclear. We retrospectively analyzed clinicopathological features, mutations in the KRAS, NRAS, and BRAF genes, as well as MSI status of 411 patients with stage I-III CRC who underwent surgery from June 2020 to December 2022 in the First Affiliated Hospital of Nanjing Medical University. The mutation rates of KRAS, NRAS, and BRAF were 48.9%, 2.2%, and 3.2%, respectively, and the microsatellite instability-high rate was 9.5%. KRAS mutation was independently associated with mucinous adenocarcinoma. Multivariate analysis suggested that tumor location and mucinous adenocarcinoma were independently associated with BRAF mutation. Only T stage was associated with NRAS mutations in the univariate analysis. Multivariate analysis revealed that factors such as larger tumor size, tumor location, younger age, and poor differentiation were independently associated with microsatellite instability-high status. The results illustrate the mutation frequencies of KRAS, NRAS, BRAF genes and MSI status in stage I-III CRC from the eastern region of China. These findings further validate the associations between these genes status and various clinicopathological characteristics.
Topics: Humans; Proto-Oncogene Proteins B-raf; Microsatellite Instability; Proto-Oncogene Proteins p21(ras); Retrospective Studies; Colorectal Neoplasms; Mutation; Adenocarcinoma, Mucinous; Membrane Proteins; GTP Phosphohydrolases
PubMed: 38579072
DOI: 10.1097/MD.0000000000037693 -
World Journal of Gastrointestinal... Mar 2024Volatile organic compounds (VOCs) are a promising potential biomarker that may be able to identify the presence of cancers.
BACKGROUND
Volatile organic compounds (VOCs) are a promising potential biomarker that may be able to identify the presence of cancers.
AIM
To identify exhaled breath VOCs that distinguish pancreatic ductal adenocarcinoma (PDAC) from intraductal papillary mucinous neoplasm (IPMN) and healthy volunteers.
METHODS
We collected exhaled breath from histologically proven PDAC patients, radiological diagnosis IPMN, and healthy volunteers using the ReCIVA device between 10/2021-11/2022. VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.
RESULTS
A total of 156 participants (44% male, mean age 62.6 ± 10.6) were enrolled (54 PDAC, 42 IPMN, and 60 controls). Among the nine VOCs identified, two VOCs that showed differences between groups were dimethyl sulfide [0.73 0.74 0.94 arbitrary units (AU), respectively; = 0.008] and acetone dimers (3.95 4.49 5.19 AU, respectively; < 0.001). After adjusting for the imbalance parameters, PDAC showed higher dimethyl sulfide levels than the control and IPMN groups, with adjusted odds ratio (aOR) of 6.98 (95%CI: 1.15-42.17) and 4.56 (1.03-20.20), respectively ( < 0.05 both). Acetone dimer levels were also higher in PDAC compared to controls and IPMN (aOR: 5.12 (1.80-14.57) and aOR: 3.35 (1.47-7.63), respectively ( < 0.05 both). Acetone dimer, but not dimethyl sulfide, performed better than CA19-9 in PDAC diagnosis (AUROC 0.910 0.796). The AUROC of acetone dimer increased to 0.936 when combined with CA19-9, which was better than CA19-9 alone ( < 0.05).
CONCLUSION
Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants. Additional prospective studies are required to validate these findings.
PubMed: 38577457
DOI: 10.4251/wjgo.v16.i3.894 -
World Journal of Gastrointestinal... Mar 2024Appendiceal mucinous neoplasms (AMNs), although not classified as rare, are relatively uncommon tumors most often discovered incidentally during colorectal surgery....
BACKGROUND
Appendiceal mucinous neoplasms (AMNs), although not classified as rare, are relatively uncommon tumors most often discovered incidentally during colorectal surgery. Accurate identification of AMNs is difficult due to non-specific symptoms, overlapping tumor markers with other conditions, and the potential for misdiagnosis. This underscores the urgent need for precision in diagnosis to prevent severe complications.
CASE SUMMARY
This case report describes the unexpected discovery and treatment of a low-grade AMN (LAMN) in a 74-year-old man undergoing laparoscopic hemicolectomy for transverse colon adenocarcinoma (AC). Preoperatively, non-specific gastrointestinal symptoms and elevated tumor markers masked the presence of AMN. The tumor, presumed to be an AMN peritoneal cyst intraoperatively, was confirmed as LAMN through histopathological examination. The neoplasm exhibited mucin accumulation and a distinct immunohistochemical profile: Positive for Homeobox protein , Cytokeratin 20, special AT-rich sequence-binding protein 2, and Mucin 2 but negative for cytokeratin 7 and Paired box gene 8. This profile aids in distinguishing appendiceal and ovarian mucinous tumors. Postoperative recovery was uncomplicated, and the patient initiated adjuvant chemotherapy for the colon AC.
CONCLUSION
This case highlights the diagnostic complexity of AMNs, emphasizing the need for vigilant identification to avert potential complications, such as pseudomyxoma peritonei.
PubMed: 38577069
DOI: 10.4240/wjgs.v16.i3.944 -
World Journal of Clinical Cases Mar 2024Appendiceal intussusception is a pathological condition in which the appendix is inverted into the cecum, which may cause symptoms that resemble those of other...
BACKGROUND
Appendiceal intussusception is a pathological condition in which the appendix is inverted into the cecum, which may cause symptoms that resemble those of other gastrointestinal disorders and may induce intestinal obstruction. The rarity of this case presentation is the co-occurrence of appendiceal intussusception and cecal adenocarcinoma, a combination that to our knowledge has not previously been reported in the medical literature. This case provides new insights into the complexities of diagnosing and managing overlapping pathologies.
CASE SUMMARY
A 25-year-old woman presented with persistent periumbilical pain and bloody stools. An initial biopsy showed cecal cancer; however, subsequent colonoscopy and computed tomography findings raised the suspicion of appendiceal intussusception, which was later confirmed postoperatively. This unique case was characterized by a combination of intussusception and adenocarcinoma of the cecum. The intervention included a laparoscopic right hemicolectomy, which led to the histopathological diagnosis of mucinous adenocarcinoma with appendiceal intussusception. The patient recovered well postoperatively and was advised to initiate adjuvant chemotherapy. This case highlights not only the importance of considering appendiceal intussusception in the differential diagnosis, but also the possibility of appendicitis and the atypical presentation of neoplastic lesions.
CONCLUSIONS
Physicians should consider the possibility of appendiceal intussusception in cases of atypical appendicitis, particularly when associated with neoplastic presentation.
PubMed: 38576819
DOI: 10.12998/wjcc.v12.i8.1461 -
Human Cell Jul 2024A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over...
A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient's tumour tissue. Notably, MTC-22 cells, and the patient's carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient's tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.
Topics: Humans; Female; Ovarian Neoplasms; Class I Phosphatidylinositol 3-Kinases; Cell Line, Tumor; Adenocarcinoma, Clear Cell; Middle Aged; Transcription Factors; DNA-Binding Proteins; Nuclear Proteins; Mutation; Point Mutation; Cell Proliferation; Phosphatidylinositol 3-Kinases
PubMed: 38573494
DOI: 10.1007/s13577-024-01058-x -
The American Journal of Surgical... May 2024The diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) can be challenging due to potential confusion with other pancreatic neoplasms, particularly...
The diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) can be challenging due to potential confusion with other pancreatic neoplasms, particularly pancreatic neuroendocrine tumors (NETs), using current pathological diagnostic markers. We conducted a comprehensive analysis of bulk RNA sequencing data from SPNs, NETs, and normal pancreas, followed by experimental validation. This analysis revealed an increased accumulation of peroxisomes in SPNs. Moreover, we observed significant upregulation of the peroxisome marker ABCD1 in both primary and metastatic SPN samples compared with normal pancreas and NETs. To further investigate the potential utility of ABCD1 as a diagnostic marker for SPN via immunohistochemistry staining, we conducted verification in a large-scale patient cohort with pancreatic tumors, including 127 SPN (111 primary, 16 metastatic samples), 108 NET (98 nonfunctional pancreatic neuroendocrine tumor, NF-NET, and 10 functional pancreatic neuroendocrine tumor, F-NET), 9 acinar cell carcinoma (ACC), 3 pancreatoblastoma (PB), 54 pancreatic ductal adenocarcinoma (PDAC), 20 pancreatic serous cystadenoma (SCA), 19 pancreatic mucinous cystadenoma (MCA), 12 pancreatic ductal intraepithelial neoplasia (PanIN) and 5 intraductal papillary mucinous neoplasm (IPMN) samples. Our results indicate that ABCD1 holds promise as an easily applicable diagnostic marker with exceptional efficacy (AUC=0.999, sensitivity=99.10%, specificity=100%) for differentiating SPN from NET and other pancreatic neoplasms through immunohistochemical staining.
Topics: Humans; Pancreatic Neoplasms; Pancreas; Carcinoma, Pancreatic Ductal; Neuroendocrine Tumors; Pancreatic Ducts; Biomarkers, Tumor; ATP Binding Cassette Transporter, Subfamily D, Member 1
PubMed: 38567813
DOI: 10.1097/PAS.0000000000002205