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Molecular Pharmaceutics May 2021Mucin 1 (MUC1) is a large, transmembrane mucin glycoprotein overexpressed in most adenocarcinomas and plays an important role in tumor progression. Regarding its... (Review)
Review
Mucin 1 (MUC1) is a large, transmembrane mucin glycoprotein overexpressed in most adenocarcinomas and plays an important role in tumor progression. Regarding its cellular distribution, biochemical features, and function, tumor-related MUC1 varies from the MUC1 expressed in normal cells. Therefore, targeting MUC1 for cancer immunotherapy and imaging can exploit the difference between cancerous and normal cells. Radiopharmaceuticals have a potential use as carriers for the delivery of radionuclides to tumors for a diagnostic imaging and radiotherapy. Several radiolabeled targeting molecules like peptides, antibodies, and aptamers have been efficiently demonstrated in detecting and treating cancer by targeting MUC1. This review provides a brief overview of the current status of developments and applications of MUC1-targeted radiopharmaceuticals in cancer imaging and therapy.
Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Cell Line, Tumor; Disease Models, Animal; Drug Carriers; Humans; Immunotherapy; Mice; Molecular Imaging; Mucin-1; Neoplasms; Radiopharmaceuticals; Xenograft Model Antitumor Assays
PubMed: 33821638
DOI: 10.1021/acs.molpharmaceut.0c01249 -
The Journal of Pathology Mar 2024Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the...
Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These included 16 patients with primary bladder adenocarcinomas and seven patients with urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome sequencing (16 patients), bulk RNA sequencing (RNA-seq) (19 patients), and single-cell RNA-seq (5 patients) were conducted for the specimens. Correlation analysis, survival analysis, and t-tests were also performed. Prevalent T>A substitutions were observed among somatic mutations, and major trinucleotide contexts included 5'-CTC-3' and 5'-CTG-3'. This pattern was mainly contributed by COSMIC signature 22 related to chemical carcinogen exposure (probably aristolochic acid), which has not been reported in bladder adenocarcinoma. Moreover, genes with copy number changes were also enriched in the KEGG term 'chemical carcinogenesis'. Transcriptomic analysis suggested high immune cell infiltration and luminal-like features in the majority of samples. Interestingly, a small fraction of samples with an APOBEC-derived mutational signature exhibited a higher risk of disease progression compared with samples with only a chemical carcinogen-related signature, confirming the molecular and prognostic heterogeneity of bladder adenocarcinoma. This study presents mutational and transcriptomic landscapes of bladder adenocarcinoma, and indicates that a chemical carcinogen-related mutational signature may be related to a better prognosis compared with an APOBEC signature in adenocarcinoma of the bladder. © 2024 The Pathological Society of Great Britain and Ireland.
Topics: Humans; Urinary Bladder; Mutation; Adenocarcinoma; Carcinogens; Prognosis
PubMed: 38180342
DOI: 10.1002/path.6239 -
Journal of Gastrointestinal Cancer Mar 2023Small intestinal cancers have a non-specific clinical presentation and hence a delayed diagnosis. The prevalence of small intestinal cancers is low, and there are no...
PURPOSE
Small intestinal cancers have a non-specific clinical presentation and hence a delayed diagnosis. The prevalence of small intestinal cancers is low, and there are no cost-effective methods of screening. This study aimed to identify clinical characteristics of duodenal and jejunal adenocarcinomas that can assist in the early detection and diagnosis of disease.
METHODS
Duodenal adenocarcinoma and jejunal adenocarcinoma in Explorys database (1999-2019) were compared using odds ratio (OR) with 95% confidence intervals. Data on demographic characteristics, risk factors, clinical features, and treatment were collected.
RESULTS
Out of a total of 8100 patients with a diagnosis of primary adenocarcinoma of the small intestine, 5110 are primary adenocarcinoma of duodenum (63%), and 600 are primary adenocarcinoma of jejunum (7.4%). Patients with jejunal adenocarcinoma when compared with patients with duodenal adenocarcinoma are more obese (OR, 1.36) and have a significantly higher prevalence of malignant neoplasm of colon (OR, 3.07), Crohn's disease (OR, 4.42), and celiac disease (OR, 2.48). Jejunal adenocarcinoma patients presented more frequently with intestinal obstruction (OR, 1.99), whereas duodenal adenocarcinoma patients more commonly presented with iron deficiency anemia (OR, 0.16). Patients with jejunal adenocarcinoma are less likely to undergo therapy with anti-neoplastic agents when compared with duodenal adenocarcinoma (OR, 0.81). There are no differences in patients undergoing surgical intervention or a combination of surgical intervention and antineoplastic therapy.
CONCLUSIONS
Jejunal adenocarcinoma is more commonly associated with colorectal cancer, celiac disease, and Crohn's disease. They also had lower odds of requiring chemotherapeutic agents.
Topics: Humans; Crohn Disease; Celiac Disease; Intestine, Small; Jejunal Neoplasms; Duodenal Neoplasms; Ileal Neoplasms; Adenocarcinoma
PubMed: 35001295
DOI: 10.1007/s12029-021-00653-7 -
Abdominal Radiology (New York) Nov 2022This study aimed to analyze the clinicopathological and computed tomography (CT) findings of papillary gastric adenocarcinoma and to evaluate the feasibility of the...
PURPOSE
This study aimed to analyze the clinicopathological and computed tomography (CT) findings of papillary gastric adenocarcinoma and to evaluate the feasibility of the multivariate model based on clinical information and CT findings for discriminating papillary gastric adenocarcinomas.
METHODS
This retrospective study included 22 patients with papillary gastric adenocarcinoma and 88 patients with tubular adenocarcinoma. The demographic data, tumor markers, histopathological information, CT morphological characteristics, and CT value-related parameters of all patients were collected and analyzed. The multivariate model based on regression analysis was performed to improve the diagnostic efficacy for discriminating papillary gastric adenocarcinomas preoperatively. The diagnostic performance of the established nomogram was evaluated by receiver operating characteristic curve analysis.
RESULTS
The distribution of age, carcinoembryonic antigen, differentiation degree, neural invasion, human epidermal growth factor receptor 2 overexpression, P53 mutation status, 4 CT morphological characteristics, and 10 CT valued-related parameters differed significantly between papillary gastric adenocarcinoma and tubular adenocarcinoma groups (all p < 0.05). The established multivariate model based on clinical information and CT findings for discriminating papillary gastric adenocarcinomas preoperatively achieved the area under the curve of 0.920.
CONCLUSION
There existed differences in clinicopathological features and CT findings between papillary gastric adenocarcinomas and tubular adenocarcinomas. The combination of demographic data, tumor markers, CT morphological characteristics, and CT value-related parameters could discriminate papillary gastric adenocarcinomas preoperatively with satisfactory diagnostic efficiency.
Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Antigens, Differentiation; Biomarkers, Tumor; Humans; Lung Neoplasms; Retrospective Studies; Stomach Neoplasms; Tomography, X-Ray Computed; Tumor Suppressor Protein p53
PubMed: 35972549
DOI: 10.1007/s00261-022-03635-w -
Journal of the Neurological Sciences Nov 2023The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response...
OBJECTIVE
The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response has been reported. Here, we investigated the frequency of cancer in a large cohort of patients with AQP4-IgG-NMOSD.
METHODS
Between May 2005 and January 2023, patients with AQP4-IgG-NMOSD and a history of cancer were included by searching for diagnostic codes of both NMOSD and cancer in the electronic medical records and/or reviewing the database of the National Cancer Center registry of inflammatory diseases of the central nervous system. Probable paraneoplastic AQP4-IgG-NMOSD was defined according to the 2021 Criteria for Paraneoplastic Neurological Syndrome.
RESULTS
Of 371 patients with AQP4-IgG-NMOSD, 23 (6.2%) had a history of cancer and four (1.1%) experienced NMOSD in a paraneoplastic context. Among the four patients with probable paraneoplastic AQP4-IgG-NMOSD, the types of cancer were lung (1 adenocarcinoma, 1 squamous cell carcinoma) and colorectal (2 adenocarcinomas). In three patients, the first NMOSD symptoms developed after a cancer diagnosis (median, 8 months [range, 4-23]), and one patient's symptoms preceded the cancer diagnosis (6 months). Compared to the 367 non-paraneoplastic patients, those in the paraneoplastic context had an older age at onset (median: 59.5 vs. 37 years, p = 0.012) and a higher proportion of longitudinally extensive transverse myelitis (LETM) as an initial manifestation (4/4[100%] vs. 130/367[35.4%], p = 0.017).
CONCLUSIONS
In a large cohort of patients with AQP4-IgG-NMOSD, the frequency of cancer was low. Older age, LETM features at onset, and adenocarcinoma as the histological type were usually observed in patients with AQP4-IgG-NMOSD in a paraneoplastic context.
Topics: Humans; Neuromyelitis Optica; Aquaporin 4; Myelitis, Transverse; Autoantibodies; Adenocarcinoma; Immunoglobulin G
PubMed: 37813018
DOI: 10.1016/j.jns.2023.120825 -
Thoracic Cancer Oct 2023Lung adenocarcinomas with micropapillary pattern (MP) or solid pattern (SP) have poor prognosis with frequent postoperative recurrence. However, treatment strategies for...
BACKGROUND
Lung adenocarcinomas with micropapillary pattern (MP) or solid pattern (SP) have poor prognosis with frequent postoperative recurrence. However, treatment strategies for these histological subtypes have not been established. This study examined the recurrence rates and patterns in patients with these histological subtypes.
METHODS
Overall, 238 patients with lung adenocarcinoma who underwent radical resection were included. According to the histological subtypes, the patients were classified into three groups: neither MP nor SP (MP-/SP-), MP (MP+), and SP (SP+). The clinical and pathological characteristics and recurrence-free survival (RFS) were examined in each group. In addition, univariate and multivariate analyses were performed to investigate the recurrence factors. The site of recurrence, PD-L1 expression, and driver mutations were examined in patients with postoperative recurrence.
RESULTS
The recurrence rates were significantly higher in the MP+ and SP+ groups (p = 0.01). The RFS was significantly shorter in the MP+ and SP+ groups (p < 0.001) than in the MP-/SP- group, especially in pStage 1A (p = 0.001). The relationship between recurrence and pathologic factors was significant for pleural, lymphatic, and vascular invasion, as well as MP in univariate analysis and only for MP in multivariate analysis. Most recurrences were distant metastases in the MP+ and SP+ groups. PD-L1 was highly expressed in recurrent SP+ cases.
CONCLUSIONS
Early-stage lung adenocarcinoma with MP or SP frequently has postoperative recurrence. Prevention of distant metastases is important in these patients to improve prognosis, and aggressive postoperative chemotherapy may be considered.
Topics: Humans; B7-H1 Antigen; Lung Neoplasms; Adenocarcinoma; Neoplasm Staging; Neoplasm Recurrence, Local; Adenocarcinoma of Lung; Prognosis; Retrospective Studies
PubMed: 37658844
DOI: 10.1111/1759-7714.15087 -
Lung Cancer (Amsterdam, Netherlands) Jun 2023Genetic changes that drive the transition from lepidic to invasive cancer development within a radiographic ground glass or semi-solid lung lesion (SSL) are not well...
BACKGROUND
Genetic changes that drive the transition from lepidic to invasive cancer development within a radiographic ground glass or semi-solid lung lesion (SSL) are not well understood. Biomarkers to predict the transition to solid, invasive cancer within SSL are needed.
METHODS
Patients with surgically resected SSL were identified retrospectively from a surgical database. Clinical characteristics and survival were compared between stage I SSL (n = 65) and solid adenocarcinomas (n = 120) resected during the same time period. Areas of normal lung, in situ lepidic, and invasive solid tumor were microdissected from within the same SSL specimens and next generation sequencing (NGS) and Affymetrix microarray of gene expression were performed.
RESULTS
There were more never smokers, Asian patients, and sub-lobar resections among SSL but no difference in 5-year survival between SSL and solid adenocarcinoma. Driver mutations found in both lepidic and solid invasive portion were EGFR (43%), KRAS (21%), and DNMT3A (5%). CEACAM5 was the most upregulated gene found in solid, invasive portions of SSL. Lepidic and invasive solid areas had many similarities in gene expression, however there were some significant differences with the gene SPP1 being a unique biomarker for the invasive component of a SSL.
CONCLUSIONS
Common lung cancer driver mutations are present in in situ lepidic as well as invasive solid portions of a SSL, suggesting early development of driver mutations. CEACAM5 and SPP1 emerged as promising biomarkers of invasive potential in semi-solid lesions. Other studies have shown both genes to correlate with poor prognosis in lung cancer and their role in evolution of semi-solid lung lesions warrants further study.
Topics: Humans; Lung Neoplasms; Retrospective Studies; Adenocarcinoma of Lung; Adenocarcinoma; Genomics
PubMed: 37121213
DOI: 10.1016/j.lungcan.2023.107211 -
Journal of Gastroenterology and... Oct 2023The endoscopic features of gastric neuroendocrine carcinoma (G-NEC) have not been clarified; therefore, they were investigated in relation to clinicopathological...
BACKGROUND AND AIM
The endoscopic features of gastric neuroendocrine carcinoma (G-NEC) have not been clarified; therefore, they were investigated in relation to clinicopathological findings.
METHODS
Consecutive patients with G-NECs who had undergone endoscopic or surgical resection at our institution between January 2005 and March 2022 were included in this retrospective study. The endoscopic and clinicopathological findings of the lesions were analyzed to provide information of diagnostic value. In addition, cases of gastric neuroendocrine tumor (G-NET) and common-type gastric adenocarcinoma treated in the same study period were identified to compare the endoscopic findings between each G-NEC versus G-NET, and G-NEC versus common-type gastric adenocarcinoma. Patients with common-type gastric adenocarcinoma were matched for age, sex, tumor size, and depth of tumor invasion in 1:3 ratio.
RESULTS
Among 15 patients with 15 G-NECs, submucosal tumor-like marginal elevation (87%), adherent white coat (67%), and ulceration with a distinct border (60%) were characteristic endoscopic findings in white-light images. Magnifying narrow-band imaging endoscopy revealed an absent microsurface (MS) pattern plus disrupted irregular microvessel (MV) in five (71%) of seven cases with evaluable MS and MV patterns. The area with an absent MS pattern plus disrupted irregular MV corresponded to the histological finding of NEC component in all five cases. These endoscopic features were all significantly more frequent in G-NECs than G-NETs (n = 22) or common-type gastric adenocarcinomas (n = 45).
CONCLUSIONS
These endoscopic features should be taken into consideration to increase the index of suspicion and to improve the accuracy of target biopsies for G-NEC.
Topics: Humans; Retrospective Studies; Carcinoma, Neuroendocrine; Adenocarcinoma; Neuroendocrine Tumors; Stomach Neoplasms; Endoscopy, Gastrointestinal
PubMed: 37527834
DOI: 10.1111/jgh.16309 -
Surgery Today Aug 2020The definition of true esophagogastric junction (EGJ) adenocarcinoma and its surgical treatment are debatable. We review the basis for the current definition and the... (Review)
Review
The definition of true esophagogastric junction (EGJ) adenocarcinoma and its surgical treatment are debatable. We review the basis for the current definition and the Japanese surgical strategy in managing true EGJ adenocarcinoma. The Siewert classification is a well-known anatomical classification system for EGJ adenocarcinomas: type II tumors in the region 1 cm above and 2 cm below the EGJ are described as "true carcinoma of the cardia". Coincidentally, this range matches gastric cardiac gland distribution. Conversely, Nishi's classification is generally used to describe EGJ carcinomas, defined as tumors with the center located within 2 cm above and 2 cm below the EGJ, regardless of their histological subtype. This range coincides with the extent of the lower esophageal sphincter combined with gastric cardiac gland distribution. The current Japanese surgical strategy focuses on the tumor range from the EGJ to the esophagus and stomach. According to previous studies, the strategy can be roughly classified into three types. The optimal surgical procedure for true EGJ adenocarcinoma is controversial. However, an ongoing Japanese nationwide prospective trial will help confirm the appropriate standard surgery, including the optimal extent of lymph node dissection.
Topics: Adenocarcinoma; Digestive System Surgical Procedures; Esophageal Neoplasms; Esophagogastric Junction; Gastric Mucosa; Humans; Lymph Node Excision; Stomach Neoplasms
PubMed: 31278583
DOI: 10.1007/s00595-019-01843-4 -
JAMA Network Open Oct 2023It is currently unclear whether high-resolution computed tomography can preoperatively identify pathologic tumor invasion for ground-glass opacity lung adenocarcinoma.
IMPORTANCE
It is currently unclear whether high-resolution computed tomography can preoperatively identify pathologic tumor invasion for ground-glass opacity lung adenocarcinoma.
OBJECTIVES
To evaluate the diagnostic value of high-resolution computed tomography for identifying pathologic tumor invasion for ground-glass opacity featured lung tumors.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, multicenter diagnostic study enrolled patients with suspicious malignant ground-glass opacity nodules less than or equal to 30 mm from November 2019 to July 2021. Thoracic high-resolution computed tomography was performed, and pathologic tumor invasion (invasive adenocarcinoma vs adenocarcinoma in situ or minimally invasive adenocarcinoma) was estimated before surgery. Pathologic nonadenocarcinoma, benign diseases, or those without surgery were excluded from analyses; 673 patients were recruited, and 620 patients were included in the analysis. Statistical analysis was performed from October 2021 to January 2022.
EXPOSURE
Patients were grouped according to pathologic tumor invasion.
MAIN OUTCOMES AND MEASURES
Primary end point was diagnostic yield for pathologic tumor invasion. Secondary end point was diagnostic value of radiologic parameters.
RESULTS
Among 620 patients (442 [71.3%] female; mean [SD] age, 53.5 [12.0] years) with 622 nodules, 287 (46.1%) pure ground-glass opacity nodules and 335 (53.9%) part-solid nodules were analyzed. The median (range) size of nodules was 12.1 (3.8-30.0) mm; 47 adenocarcinomas in situ, 342 minimally invasive adenocarcinomas, and 233 invasive adenocarcinomas were confirmed. Overall, diagnostic accuracy was 83.0% (516 of 622; 95% CI, 79.8%-85.8%), diagnostic sensitivity was 82.4% (192 of 233; 95% CI, 76.9%-87.1%), and diagnostic specificity was 83.3% (324 of 389; 95% CI, 79.2%-86.9%). For tumors less than or equal to 10 mm, 3.6% (8 of 224) were diagnosed as invasive adenocarcinomas. The diagnostic accuracy was 96.0% (215 of 224; 95% CI, 92.5%-98.1%), diagnostic specificity was 97.2% (210 of 216; 95% CI, 94.1%-99.0%); for tumors greater than 20 mm, 6.9% (6 of 87) were diagnosed as adenocarcinomas in situ or minimally invasive adenocarcinomas. The diagnostic accuracy was 93.1% (81 of 87; 95% CI, 85.6%-97.4%) and diagnostic sensitivity was 97.5% (79 of 81; 95% CI, 91.4%-99.7%). For tumors between 10 to 20 mm, the diagnostic accuracy was 70.7% (220 of 311; 95% CI, 65.3%-75.7%), diagnostic sensitivity was 75.0% (108 of 144; 95% CI, 67.1%-81.8%), and diagnostic specificity was 67.1% (112 of 167; 95% CI, 59.4%-74.1%). Tumor size (odds ratio, 1.28; 95% CI, 1.18-1.39) and solid component size (odds ratio, 1.31; 95% CI, 1.22-1.42) could each independently serve as identifiers of pathologic invasive adenocarcinoma. When the cutoff value of solid component size was 6 mm, the diagnostic sensitivity was 84.6% (95% CI, 78.8%-89.4%) and specificity was 82.9% (95% CI, 75.6%-88.7%).
CONCLUSIONS AND RELEVANCE
In this diagnostic study, radiologic analysis showed good performance in identifying pathologic tumor invasion for ground-glass opacity-featured lung adenocarcinoma, especially for tumors less than or equal to 10 mm and greater than 20 mm; these results suggest that a solid component size of 6 mm could be clinically applied to distinguish pathologic tumor invasion.
Topics: Humans; Female; Middle Aged; Male; Prospective Studies; Adenocarcinoma of Lung; Lung Neoplasms; Adenocarcinoma; Tomography, X-Ray Computed
PubMed: 37843862
DOI: 10.1001/jamanetworkopen.2023.37889