Pathological Specimens Research Articles

P1.06C.01 Evaluation of Small Pulmonary Pathology Specimen Management in the Province of Quebec, Canada

P1.06C.01 Evaluation of Small Pulmonary Pathology Specimen Management in the Province of Quebec, Canada

Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants.

Germline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated. To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs. This case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023. Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens. All 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas. Patients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.

Prognostic impact of caspase-8 mutation in oral cavity squamous cell carcinoma.

Identifying the drive genes and inhibiting their significant signals were persistently the main concepts in cancer treatment. However, for oral cavity squamous cell carcinoma (OCSCC), the most influential genes for overall survival (OS) remain unclear. A total of 120 OCSCC patients with corresponding pathologic specimens were collected in Taiwan. Whole-exome sequencing was done and the prognostic impact of each gene was analyzed. TCGA database was used to validate. The incidences of caspase-8 mutation were 22.1% and 10.9% in the Taiwan and TCGA cohort, respectively. In the Taiwan cohort, caspase-8 mutation was the most significant independent for OS with an adjusted hazard ratio (HR) ([95% CI]: 3.83 [1.84-7.99]). It was validated by the TCGA database (HR [95% CI]: 1.51 [1.00-2.29]). The 5-year OSs of the patients with or without caspase-8 mutation were 38.1% vs. 75.3% (p < 0.001) (HR [95% CI]: 3.264 [1.645-6.438]) in the Taiwan cohort, and 26.1% vs. 49.0% (p = 0.048) (1.513 [1.001-2.288]) in the TCGA cohorts, respectively. Caspase-8 mutation was also individually associated with poor prognosis for TNM stage I/II/III/IV, respectively. CASP8 R127* and R494*, defined as pathogenic mutations in ClinVar, were presented in both cohorts. Caspase-8 mutation was the most significant genetic alteration impacting prognosis.

Machine Learning for the Prediction of Surgical Morbidity in Placenta Accreta Spectrum.

We sought to create a machine learning (ML) model to identify variables that would aid in the prediction of surgical morbidity in cases of placenta accreta spectrum (PAS). A multicenter analysis including all cases of PAS identified by pathology specimen confirmation, across five tertiary care perinatal centers in New York City from 2013 to 2022. We developed models to predict operative morbidity using 213 variables including demographics, obstetrical information, and limited prenatal imaging findings detailing placental location. Our primary outcome was prediction of a surgical morbidity composite defined as including any of the following: blood loss (>1,500 mL), transfusion, intensive care unit admission, vasopressor use, mechanical ventilation/intubation, and organ injury. A nested, stratified, cross-validation approach was used to tune model hyperparameters and estimate generalizability. Gradient boosted tree classifier models incorporated preprocessing steps of standard scaling for numerical variables and one-hot encoding for categorical variables. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), positive and negative predictive values (PPV, NPV), and F1 score. Variable importance ranking was also determined. Among 401 PAS cases, 326 (81%) underwent hysterectomy. Of the 401 cases of PAS, 309 (77%) had at least one event defined as surgical morbidity. Our predictive model had an AUC of 0.79 (95% confidence interval: 0.69, 0.89), PPV 0.79, NPV 0.76, and F1 score of 0.88. The variables most predictive of surgical morbidity were completion of a hysterectomy, prepregnancy body mass index (BMI), absence of a second trimester ultrasound, socioeconomic status zip code, BMI at delivery, number of prenatal visits, and delivery time of day. By identifying social and obstetrical characteristics that increase patients' risk, ML models are useful in predicting PAS-related surgical morbidity. Utilizing ML could serve as a foundation for risk and complexity stratification in cases of PAS to optimize surgical planning. · ML models are useful models are useful in predicting PAS-related surgical morbidity.. · Optimal management for PAS remains unclear.. · Utilizing ML can serve as a foundation for risk and complexity stratification in cases of PAS..

Histopathologic Analysis of Chronic Cutaneous Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. Skin biopsy of cGVHD is recommended when clinical features are not diagnostic, yet the histopathologic features of skin cGVHD are not well described. The objective of this study is to describe the histopathologic features of skin cGVHD in epidermal, sclerotic, and combination cGVHD. Of 49 patients with skin cGVHD, 30 of 49 (61.2%) were male, and mean age was 55 years (SD 11.1). Clinically, 33 of 49 (67.3%) had epidermal cGVHD (E-cGVHD), 1 of 49 (2.1%) had sclerotic cGVHD (S-cGVHD), and 15 of 49 (30.6%) had combination disease. The 49 patients corresponded to 83 unique pathologic specimens with 67 of 83 (80.7%) taken from E-cGVHD, and 16 of 83 (19.3%) from S-cGVHD lesions. Nearly all biopsy specimens from E-cGVHD showed minimal features of active GVHD, including apoptosis in the epidermal basal layer (n = 63, 94.0%), vacuolar change (n = 62, 92.5%), and lymphocyte satellitosis (n = 57, 85.1%). The predominant histologic pattern of E-cGVHD was lichen planus/interface dermatitis (n = 31, 47.0%). S-cGVHD specimens also showed minimal features of active GVHD with apoptosis of the epidermal basal layer (n = 11, 68.8%) and vacuolar change (n = 8, 50.0%). In addition, S-cGVHD showed sclerosis of the papillary and reticular dermis and subcutaneous septae (n = 8, 50.0%; n = 11, 68.8%; n = 5, 31.2%, respectively). The predominant histologic pattern of S-cGVHD was lichen sclerosus/morphea-like pattern (n = 10, 62.5%). Although minimal pathologic features of active GVHD are common, the majority of cGVHD biopsies share features with the inflammatory skin diseases that they clinically resemble. Complete histologic reporting is recommended with implications for disease endotyping and personalized therapy.

Quantitative cytoarchitectural phenotyping of deparaffinized human brain tissues.

Advanced 3D imaging techniques and image segmentation and classification methods can profoundly transform biomedical research by offering deep insights into the cytoarchitecture of the human brain in relation to pathological conditions. Here, we propose a comprehensive pipeline for performing 3D imaging and automated quantitative cellular phenotyping on Formalin-Fixed Paraffin-Embedded (FFPE) human brain specimens, a valuable yet underutilized resource. We exploited the versatility of our method by applying it to different human specimens from both adult and pediatric, normal and abnormal brain regions. Quantitative data on neuronal volume, ellipticity, local density, and spatial clustering level were obtained from a machine learning-based analysis of the 3D cytoarchitectural organization of cells identified by different molecular markers in two subjects with malformations of cortical development (MCD). This approach will grant access to a wide range of physiological and pathological paraffin-embedded clinical specimens, allowing for volumetric imaging and quantitative analysis of human brain samples at cellular resolution. Possible genotype-phenotype correlations can be unveiled, providing new insights into the pathogenesis of various brain diseases and enlarging treatment opportunities.

Study on the complications after implantation of different types of metal stents in rabbit trachea

ObjectiveTo observe the complications and inflammatory responses caused by the different types of metal stents in the trachea of rabbits. Method79 rabbits were randomly divided into 4 groups and were implanted with the customized nickel-titanium alloy metal stents(fully covered metal stent: group A, bare metal stent: group B, segmented covered metal stent: group C and control group: group D). The complications (tracheal deformation, granulation tissue hyperplasia, scar hyperplasia and secretion retention) of different types of metal stents were compared by observing the anatomical and pathological specimens of dead rabbits; And the expression of inflammatory factors of different types of metal stents were compared by detecting the tissue of tracheas of dead rabbits. Results(1)There were significant differences in the above four complications among groups A, B and C(p < 0.01). The incidences of tracheal deformation, scar hyperplasia and secretion retention in group A were significantly higher than that in group B(p < 0.0167), however, the incidence of granulation tissue hyperplasia in group A was significantly lower than that in group B(p < 0.0167). The incidence of scar hyperplasia in group A was significantly lower than that in group C(p < 0.0167) and there were no significant differences in other complications between these two groups(p > 0.0167). The incidences of tracheal deformation, scar hyperplasia and secretion retention in group B were significantly lower than that in group C(p < 0.0167), however, the incidence of granulation tissue hyperplasia in group B was significantly higher than that in group C(p < 0.0167). (2)The concentration of IL-1β in group A was higher than that in group B (p < 0.05 and foldchange>1.2). Conclusion(1)There are significant differences in complications between the fully covered metal stent, bare metal stent and segmented covered metal stent; the incidences of complications between the segmented covered metal stent and fully covered metal stent are similar. (2)Changes in different inflammatory factors can be observed between the fully covered and bare metal stent.

Classification of Gastric Neuroendocrine Tumors and Associations With Survival.

Not all gastric neuroendocrine tumors (GNETs) may be classified into one of the three described clinicopathologic subtypes. The purpose of this study was to better characterize GNET subtypes and associated outcomes. Patients treated for GNET at our institution (1995-2021) were identified. Pathologic specimens of tumors that could not be classified as type 1, 2, or 3 were further reviewed. GNETs were categorized as proton pump inhibitor (PPI)-associated based on changes in the background gastric mucosa consistent with PPI use. Distant metastasis at presentation (DM) and disease-specific survival (DSS) were evaluated. Among 246 patients, there were 164 (67%) type 1, 5 (2%) type 2, 52 (21%) type 3, and 18 (7%) PPI-associated GNETs. Seven (3%) tumors remained unclassified. DM was more frequent with type 3 GNETs (38%) than type 1 (1%), type 2 (20%), or PPI-associated tumors (11%, p < 0.001). Ten-year DSS rates were 100% for type 1, 53% (95% confidence interval [CI], 38%-75%) for type 3, and 80% (95% CI, 58%-100%) for PPI-associated tumors (p < 0.001). GNET subtype, race, and DM were independently associated with DSS. PPI-associated tumors may represent a distinct GNET subtype with intermediate outcomes. Other factors should also be considered in overall prognosis.

Impact of cyclophosphamide on the morphological and histological changes in polyglycolic acid spacers.

In radiotherapy for pediatric abdominal tumors, determining the effect of concurrent chemotherapy on polyglycolic acid (PGA) spacers is crucial; yet this effect has not been validated. Therefore, we aimed to evaluate the impact of cyclophosphamide (CPA) chemotherapy on the PGA spacer using a rat model. Twenty-four rats were implanted with the spacer, and morphological changes in the spacer were assessed on CT for both the CPA-dosed group (40mg/kg) and the control group. The size and volume of the spacer were quantified using CT, while the degree of adhesion and microscopic examination of the tissue were determined using pathology specimens. Morphologically, the size of the spacer decreased over time in both the CPA-dosed and control groups, with no significant differences observed between groups. No significant differences in adhesion were observed between the two groups. Macrophages were observed around the PGA fibers, suggesting their involvement in the degradation of the PGA spacer. These results suggest that CPA does not cause significant clinically problematic degradation or adverse tissue reactions to the PGA spacer. This study reinforced the benefits of PGA spacers; however, future research focusing on in vivo longitudinal monitoring of individual rats, as well as on humans, is required.

FP2.1 - The accuracy of radiological staging in rectal cancer patients post-long course chemoradiotherapy treatment

Abstract Aim Accurate post Long-course chemoradiotherapy treatment (LCCRT) allows safe selection of patients to rectal preservation without delaying resection in those with residual cancer. The aim of this study was to assess the accuracy of radiological staging in these patients. Methods Demographic and treatment data from consecutive patients receiving LCCRT for rectal cancer between May 2020 to December 2021 was collected. Local radiological staging post-LCCRT treatment was compared to pathological staging. Where patients had complete radiological response (CRR) and opted for watch and wait (WW) those with demonstrable local recurrence, within 12 months, were assumed to have been under-staged. Results Of 61 patients, 37 underwent surgical resection following LCCRT and 24 watch and wait for CRR. Post-LCCRT imaging was taken at a median of 10.86 weeks (IQR, 8.86- 13.00) post completion of treatment and resections 16.57 weeks (IQR 9.71 – 23.00) post-imaging. Four WW patients were diagnosed with local recurrence at a median of 56.54 weeks of follow-up (IQR, 39.9 – 67.90). The ratio of patients radiologically staged as T0:T1:T2:T3:T4 was 15%: 0%: 28%: 46%: 10%; whilst the pathology specimens demonstrated 20%: 5%: 12%: 49%: 15% respectively. Nodal staging (N0:N1:N2) was 78%: 20%: 2% with histology showing 71%: 24%: 5% respectively. Conclusion In our low-numbered study T-staging of patients with T0 and T1 disease had highest rates of over-staging such that 2 (5%) patients for potential watch and wait were not recognised as CCR by MRI alone. Nodal staging appeared more accurate although a tendency to under-stage N0 disease was seen.

Short-term outcomes of Transrectal Natural Orifice Specimen extraction compared with conventional minimally invasive surgery for selected patients with colorectal cancer: a propensity score matching analysis and literature review

PurposeConventional minimally invasive surgery requires mini-laparotomy to extract the pathological specimen. However, by using a natural orifice as the delivery route, natural orifice specimen extraction (NOSE) surgery avoids the need for a large incision. This study analyzed the short-term outcome of NOSE compared with conventional mini-laparotomy (CL) for colorectal cancer surgery.MethodsWe conducted a retrospective analysis of 1,189 patients who underwent surgery for primary colorectal cancer between the cecum and upper rectum. Propensity score analyses were applied to the NOSE and CL groups in a 1:1 matched cohort.ResultsAfter propensity score matching, each group included 201 patients. The NOSE group and CL group did not differ significantly in terms of baseline characteristics. Postoperative morbidity and mortality rates were comparable. Compared with the CL group, the NOSE group experienced a shorter time to first flatus (1.6 ± 0.8 vs. 2.0 ± 1.2 days, p < 0.001), first stool (2.7 ± 1.5 vs. 4.1 ± 1.9, p < 0.001), liquid diet (2.3 ± 1.3 vs. 3.6 ± 1.8 days, p < 0.001), soft diet (3.9 ± 2.0 vs. 5.2 ± 1.9 days, p < 0.001) and a shorter hospital stay (5.1 ± 3.5 vs. 7.4 ± 4.8 days, p < 0.001). The NOSE group exhibited lower mean pain intensity and lower highest pain intensity on postoperative days 1, 2, and 3.ConclusionNOSE has several advantages over conventional mini-laparotomy following minimally invasive surgery for colon cancer. These advantages include reduced time to oral intake, shorter hospital stays, and less postoperative pain. NOSE can be adopted and applied to highly selective patients without additional risk of short-term complications.

Adverse tissue reactions to ORISE gel during endoscopic mucosal resection and dissection

BackgroundSubmucosal injection of lifting agents (LAs) is frequently used to facilitate endoscopic mucosal resection or endoscopic submucosal dissection. ORISE (Boston Scientific Corporation) gel, approved in 2018 by the United States Food and Drug Administration, has been commonly used until recently. Its use proliferated because of its practical prefilled syringe, prolonged lift effect, and ideal coloration. However, it has been noted to cause unexpected tissue reactions, described as “giant cell reaction” (GCR), which can obscure macroscopic and microscopic views, potentially interfering with pathologic evaluation. This study aimed to describe the adverse effects of ORISE gel. MethodsThis retrospective study analyzed pathologic specimens from all consecutive patients who received ORISE injections for attempted polyp removal and subsequently underwent segmental colon resection at our center between 2019 and 2022. A descriptive analysis was performed. ResultsA total of 45 patients were included, of whom 17 (38.0%) were female and the median age was 66 years. The indications for surgery included adenocarcinoma in 14 patients (31%), suspected malignancy in 3 patients (7%) who had benign GCR-induced masses, and other indications in 28 patients, such as large polyps or recurrent polyps after initial endoscopic treatment. Surgical procedures included right hemicolectomy (44%), low anterior resection (13%), left colectomy (11%), sigmoidectomy (7%), and abdominoperineal resection (4%). Histologic evidence of previous LA injection was seen in 31 patients (69%), with 24 patients exhibiting GCR. At final pathology, no residual neoplasm was found in 9 patients (18%); however, 14 patients (31%) had adenocarcinoma (T1 [7], T2 [3], T3 [3], and T4 [1]). ConclusionORISE gel interacts with various tissue layers of the colon, frequently resulting in GCR. This reaction and the potential subsequent mass effect formation can affect decision-making regarding the management of complex colorectal lesions. Further study into the causes and consequences of LA tissue reactions is warranted.

604. REAL-WORLD MANAGEMENT AND OUTCOMES OF PATIENTS WITH NON METASTATIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN THE FREGAT DATABASE

Abstract Background International guidelines for locally advanced esophageal squamous cell carcinoma (ESCC) recommend both neoadjuvant chemoradiotherapy (nCRT) followed by planned surgery (P-surg) or definitive chemoradiotherapy (dCRT) with salvage surgery (S-surg). However, the optimal treatment remains unknown, and the ongoing pragmatic NEEDS randomized trial is assessing the efficacy of an organ-preserving strategy after dCRT (Nilsson, Front Oncol 2022). Real-world data on the management of non-metastatic ESCC is limited. This study aims to describe the treatment strategies and prognosis of patients with non-metastatic ESCC in a real-world setting. Methods We conducted a retrospective cohort study of patient treated for non-metastatic ESCC between 2014 and 2022. Data were extracted from the FREGAT database. For the entire population, different treatment strategies were described. We compared patients who received nCRT with those who received dCRT under real-life conditions (“Real-life” population) and according to the NEEDS randomized trial criteria (“NEEDS-like” population). Five-year overall survival (OS) and relapse-free survival (RFS) were compared between nCRT and dCRT patients using a Cox proportional hazard model adjusting for major confounders. In operated patients, the impact of surgery on OS and RFS was assessed using a time-dependent Cox proportional hazard model. Postoperative outcomes were compared between P-surg and S-surg using Fisher’s exact test. Results From 971 patients diagnosed with non-metastatic ESCC, 867 (89.3%) received a curative treatment including dCRT (41.0%), nCRT (28.0%), primary esophagectomy (9.8%), neoadjuvant chemotherapy (3.4%), or endoscopic resection (1.0%). Fifty-nine patients (6,1%) received supportive care or chemotherapy alone. Forty-five patients (4.6%) died during or before treatment. In the “real-life” population (n=659), 269 patients received nCRT and 390 patients received dCRT. A total of 229 patients (93.5%) in nCRT group underwent P-surg and S-surg was performed in 44 patients (11.3%) in dCRT group. After adjustment, dCRT was associated with a significantly poorer 5-year OS and RFS (respectively HR=1.83, 95%CI 1.44-2.33; HR=1.98, 95%CI 1.57-2.49). A complete clinical response (cCR) was observed in 21.6% and 29.5% of the nCRT and dCRT groups, respectively. Among cCR undergoing resection, 35.8% had residual disease on pathological specimen. Time between CRT and surgery was 58 days (IQR44-72) vs. 109 days (IQR71-278) for P-surge and S-Surg respectively. The 90-day mortality, major morbidity (Clavien-Dindo III/IV) and pulmonary complication rates were similar in both groups, except for a higher risk of anastomotic leakage after S-surg (p=0.05). In the “NEEDS-like” population (n=598), findings were consistent and comparable to those observed in the “real-life” population. Conclusion Among non-mestastatic ESCC included in the FREGAT database, 10.6% had a non-curative approach or died prematurely. Most patients underwent dCRT, with S-surg rate of only 11.3%. Neoadjuvant CRT followed by P-surg was associated with the best outcome in terms of OS and RFS in both “rela life” and “Needs-like” populations. In operated patients, postoperative outcomes were similar after nCRT and dCRT, except for a higher incidence of anastomotic leakage after S-surg. This study highlighted the therapeutic strategies used and their results in real-life conditions for non-metastatic ESCC inside the FREGAT database. The treatment option of nCRT followed by P-surg appears to remain the optimal curative treatment regimen.

343. DIAGNOSTIC VALUE OF ENDOBRONCHIAL ULTRASOUND-GUIDED TRANSESOPHAGEAL NEEDLE ASPIRATION (EBUS-TENA) IN LESIONS ADJACENT TO BOTH THE TRACHEA/BRONCHUS AND ESOPHAGUS

Abstract Objective To investigate the clinical diagnostic value of endobronchial ultrasound-guided transesophageal needle aspiration (EBUS-TENA) in lesions adjacent to both the trachea/bronchus and esophagus Methods The clinical data of 12 patients who underwent EBUS-TENA from February 2019 to February 2022 were collected. The operative physicians and nurses worked closely with each other and meticulously cared the patients. The vital signs changes were observed and recorded, as well as intraoperative adverse events and the acquired specimens. Results All the 12 patients underwent surgery successfully, and hair-like tissue strips were obtained in each case. There were 8 cases of central lung cancer and 4 cases of mediastinal tumor. The preoperative vital signs scores showed no significant difference with the intraoperative and postoperative scores (P&amp;gt;0.05). A few complications occurred, including 2 case of mild cough, 2 case of nausea and vomiting, with no symptoms of severe cough and dyspnea, haemorrhage, mediastinal infection, pneumothorax, mediastinal emphysema and other complications. Conclusion EBUS-TENA has significant effect in successfully obtaining pathological tissue specimens especially for lesions adjacent to both the trachea/bronchus and esophagus, improving disease positive diagnosis rate, reducing patients discomfort and the risk of surgery.

Intravascular ICG-enhanced NIRF-IVUS imaging to assess progressive atherosclerotic lesions in excised human coronary arteries

Indocyanine green (ICG)-enhanced intravascular near-infrared fluorescence (NIRF) imaging enhances the information obtained with intravascular ultrasound (IVUS) by visualizing pathobiological characteristics of atherosclerotic plaques. To advance our understanding of this hybrid method, we aimed to assess the potential of NIRF-IVUS to identify different stages of atheroma progression by characterizing ICG uptake in human pathological specimens. After excision, 15 human coronary specimens from 13 adult patients were ICG-perfused and imaged with NIRF-IVUS. All specimens were then histopathologically and immunohistochemically assessed. NIRF-IVUS imaging revealed colocalization of ICG-deposition to plaque areas of lipid accumulation, endothelial disruption, neovascularization and inflammation. Moreover, ICG concentrations were significantly higher in advanced coronary artery disease stages (p < 0.05) and correlated significantly to plaque macrophage burden (r = 0.67). Current intravascular methods fail to detect plaque biology. Thus, we demonstrate how human coronary atheroma stage can be assessed based on pathobiological characteristics uniquely captured by ICG-enhanced intravascular NIRF.

Tumor size measurements predicted by digital mammography, ultrasonography, and magnetic resonance imaging in primary invasive breast cancer disease

Background and objective: The size of the tumor significantly influences the prognosis and treatment approach for breast cancer patients. The aim of this study was to find the most accurate imaging method for estimating pre-treatment tumor size in women with newly diagnosed primary invasive breast cancer by comparing the predicted tumor size obtained from mammography, ultrasonography, and magnetic resonance imaging with the pathologic size obtained from the surgical specimens. Methods: This cross-sectional study included 181 primary invasive breast cancer patients from September 2021 to March 2023. The difference in tumor size was evaluated based on imaging and pathological reports. Variables such as age, breast density, and tumor characteristics like histologic type, grade, location, and side were recorded and analyzed. The American College of Radiology Breast Imaging Reporting and Data System was used for reporting. Data analysis, performed using SPSS Statistics software, included descriptive statistics, Spearman's correlation coefficient, and Lin's index. The statistical significance level was set at P &lt;0.05. Results: The mean tumor size was 29.68, 29.07, 28.37, and 27.7mm by mammography, ultrasonography, magnetic resonance imaging, and pathology, respectively. All diagnostic procedures revealed a statistically significant correlation with pathologic tumor size with the Spearman correlation test, P = 0.000. MRI had the highest Lin’s concordance correlation coefficient (0.93). Conclusion: The study determined that all imaging modalities were accurate in estimating tumor size when compared to the gold standard of pathological specimens and that magnetic resonance imaging outperformed digital mammography and ultrasonography.

Circular RNA LDLRAD3 promotes gastric cancer progression by upregulating COL4A5 through sponging miR-h37.

Circular RNAs play an important role in the development of gastric cancer (GC). circ-low-density lipoprotein receptor class A domain containing 3 (LDLRAD3) has been confirmed to be related to GC progression. miR-137 is also a suppressor in GC. However, the impact of the interaction between circ-LDLRAD3 and miR-137 on the progression of GC remains unclear at present. The study identified expression level differences of circ-LDLRAD3, miR-137, and COL4A5 in GC pathological specimens compared to normal tissue samples. Furthermore, through in vitro experiments, including flow cytometry, cell counting kit-8 (CCK-8) assays, wound healing, Western blotting, and colony formation assays, we further explored the molecular regulatory mechanisms by which these factors promote the progression of GC. In this study, circ-LDLRAD3 was confirmed to have higher expression, and miR-137 had lower expression in GC tissues and cell lines. circ-LDLRAD3 knockdown and miR-137 overexpression promoted apoptosis and inhibited proliferation, migration, and invasion in GC cell lines. Further experiments validated that COL4A5 had a positive relationship with GC and that circ-LDLRAD3 promoted the expression of COL4A5. circ-LDLRAD3 could be sponged and inhibited by miR-137 in GC cells. As a result, the promotional effect of circ-LDLRAD3 on COL4A5 was counteracted by miR-137. Our study showed that the knockdown of circ-LDLRAD3 suppressed the development of GC by regulating the miR-137/COL4A5 axis.

Zinc transporter ZnT5 is associated with epithelial mesenchymal transition via SMAD1 in breast cancer.

Zinc levels in breast cancer tissues have been reported to be higher than those in normal tissues. In addition, the expression levels of zinc transporters, including ZnT5 and ZnT6, are reportedly higher in breast cancer than in normal breast tissues. ZnT5 and ZnT6 also contribute to heterodimer formation and are involved in several biological functions. However, the functions of ZnT5 and ZnT6 heterodimers in breast cancer remain unknown. Therefore, we first investigated the immunolocalization of ZnT5 and ZnT6 in pathological breast cancer specimens and in MCF-7 and T-47D breast cancer cells. Next, we used small interfering RNA to assess cell viability and migration in ZnT5 knockdown MCF-7 and T-47D cells. Immunohistochemical analysis showed that the number of ZnT5-positive breast cancer cells was inversely correlated with the pathologic N factor status. ZnT5 knockdown had no effect on cell viability in the presence of 100 μM ZnCl2 in MCF-7 and T-47D cells. In a wound healing assay, 100 μM ZnCl2 treatment inhibited cell migration of MCF-7 and T-47D cells, whereas ZnT5 knockdown promoted cell migration, decreased E-cadherin expression and increased vimentin, slug and matrix metalloproteinase 9 expression. Antibody arrays showed that ZnT5 knockdown increased the expression of SMAD1, and that dorsomorphin treatment inhibited the promotion of migratory ability induced by ZnT5 knockdown. The results of this study revealed that both ZnT5 may be involved in less aggressive breast cancer subtypes, possibly through inhibition of cell migration.

Differential expression in potential therapeutic target protein by treatment in small cell lung cancer with and without transformation.

202 Background: Small cell lung cancer (SCLC) is a disease with a poor prognosis. Besides combination strategy with immune checkpoint inhibitors (ICIs) and cytotoxic agents, antibody-drug conjugates (ADCs) and bispecific T-cell engagers (BiTE) are being developed. These drugs target tumor-associated surface protein. Whether prior treatment affect the transition of protein expression has not been fully investigated especially in the era of ICIs. The purpose of this study is to evaluate changes in protein expression in SCLC tissues before and after treatment. Methods: We included patients diagnosed with SCLC by surgery or biopsy and underwent re-biopsy after treatment (non-transformed group) at the National Cancer Center Hospital between 2014 and 2023. Patients who were initially diagnosed with non-small cell lung cancer and underwent transformation to SCLC (transformed group) were also included. Tissues were obtained by surgery, bronchoscopy, or CT-guided biopsy with an interval of at least 100 days. We investigated clinicopathological features in paired specimens focusing on DLL3, ASCL1, NEUROD1, POU2F3, and YAP1, which have been reported to be expressed in SCLC, as well as tumor-associated surface proteins potentially related to novel drug development. Results: Fourteen non-transformed group cases and 9 transformed group cases were included. Of these, pathology specimens were evaluable in a total of 15 cases: 9 for the non-transformed group and 6 for the transformed group. The median age was 68 years, 11 (73%) were male, 11 (73%) were smokers, 8 (53%) were in clinical stages I-IIIA, 1 (7%) in stages IIIB and 6 (40%) in stage IV. Among the transformed group, 4 of them were treated by Osimertinib before transformation. Progression free survival from first-line therapy was 298 days (255-446) vs. 314 days (245-NA) and overall survival was 1239 days (567-NA) vs. NA days (517-NA), respectively for non-transformed group and transformed group. For both these group of cases, we have evaluated several protein expressions as described above. The transition of these proteins within each group is presented in the conference. Conclusions: In this study, we focused not only on proteins already reported to be expressed in SCLC, but also on proteins that are potential new therapeutic targets and evaluated changes in protein expression. [Table: see text]

Histopathological analysis potential for unveiling hormone signaling in endocrine-related tumors.

Elucidating the mechanisms of action of steroid hormones will contribute to the development of therapeutic strategies for hormone-dependent tumors. Recent advances in genetic engineering have revealed the complex and diverse mechanisms of steroid hormone signaling; however, these techniques are limited to in vitro or animal experiments. It is believed that verifying hormone signals elucidated using human pathological tissue specimens will directly aid in treatment and diagnosis. However, pathological tissue specimens are generally formalin-fixed paraffin-embedded (FFPE), and protein/gene analyses of FFPE tissues are limited. Protein detection using immunohistochemistry with specific antibodies in FFPE tissues is a classical technique essential for diagnosis and treatment decisions in various types of cancer. In steroid hormone signaling, the expression and localization of receptors, hormone-related enzymes, and proteins encoded by response genes can be clarified using immunohistochemistry. Although protein-protein interactions such as receptor dimers and DNA-binding proteins are mainly detected in vitro, they can be examined in FFPE tissues using in situ proximity ligation assays and southwestern histochemistry, respectively. Using these detection methods, including immunohistochemistry, it is possible to analyze each hormone signaling pathway in hormone-related tumors histopathologically. Although FFPE tissues still suffer from gene and protein denaturation, their advantages include the ability to retrospectively study target factors/signals and obtain spatial information through microscopy. This review describes a visualization method for elucidating steroid hormone signaling in hormone-dependent tumors using FFPE tissues.