Tumor Pathological Features Research Articles

Clinical Features of Recurrent Spinal Cord Tumors.

Only a few reports have described the clinical features of recurrent spinal cord tumors. This study aimed to report the recurrence rates (RRs), radiographic imaging, and pathological features of various histopathological recurrent spinal cord tumors using a large sample size. This study adopted the retrospective observational study design using a single-center study setting. We retrospectively reviewed 818 consecutive individuals operated for spinal cord and cauda equina tumors between 2009 and 2018 in a university hospital. We first determined the number of surgeries and then the histopathology, duration to reoperation, number of surgeries, location, degree of tumor resection, and tumor configuration of the recurrent cases. A total of 99 patients (46 men and 53 women) who underwent multiple surgeries were identified. The mean duration between the primary and second surgeries was 94.8 months. A total of 74 patients underwent surgery twice, 18 patients thrice, and 7 patients 4 or more times. The recurrence sites were broadly distributed over the spine, with mainly intramedullary (47.5%) and dumbbell-shaped (31.3%) tumors. The RRs for each histopathology were as follows: schwannoma, 6.8%; meningioma and ependymoma, 15.9%; hemangioblastoma, 15.8%; and astrocytoma, 38.9%. The RRs after total resection were significantly lower (4.4%) than that after partial resection. Neurofibromatosis-associated schwannomas had a higher RR than sporadic schwannomas (p<0.001, odds ratio [OR]=8.54, 95% confidence interval [95% CI]: 3.67-19.93). Among the meningiomas, the RR increased to 43.5% in ventral cases (p<0.001, OR=14.36, 95% CI: 3.66-55.29). Within the ependymomas, partial resection (p<0.001, OR=2.871, 95% CI: 1.37-6.03) was found to be significantly correlated with recurrence. Dumbbell-shaped schwannomas exhibited a higher RR than non-dumbbell-shaped ones. Furthermore, dumbbell-shaped tumors other than schwannoma had a higher RR than dumbbell-shaped schwannomas (p<0.001, OR=16.0, 95% CI: 5.518-46.191). Aiming for total resection is essential to prevent recurrence. Dumbbell-shaped schwannomas and ventral meningiomas exhibited higher RR requiring revision surgery. As for dumbbell-shaped tumors, spinal surgeons should pay attention to the possibilities of non-schwannoma histopathologies.

Pathologic, immunologic, and clinical analysis of the microsatellite instability phenotype in endometrial carcinoma

The objective of this study was to determine if quantifying the microsatellite instability (MSI) phenotype could serve as a biomarker for clinical and immunologic features of deficient mismatch repair (dMMR) endometrial cancer (EC). Patients with EC undergoing hysterectomy whose tumors demonstrated dMMR were included. Immunohistochemistry (IHC) of mismatch repair proteins and polymerase chain reaction analysis of NR27, BAT25, BAT26, NR24, and NR21 microsatellite loci were performed on each case. The MSI phenotype was quantified by subtracting the number of nucleotides of each microsatellite in tumor tissue from the corresponding microsatellite in paired normal tissue and summing the absolute differences. This was termed marker sum (MS)and is a novel quantification. Tumor-infiltrating lymphocytes (TILs) were identified by IHC for CD3, CD4, and CD8 and quantified with digital image analysis. Tumor infiltration of lymphocytes and clinical characteristics were stratified by MS. Four hundred fifty-nine consecutive patients with dMMR EC were analyzed. MS ranged from 1 to 32. Post hoc, 2 cohorts were defined using receiver operating characteristic curves(MS less than 13 and MS greater than 12). With the exception of tumor grade, all clinical and pathologic features, all tumor characteristics, and the numbers of TILs were similar between cohorts. The MSI phenotype is highly variable in dMMR EC, and no correlation between the immune profile and the severity of the MSI phenotype was observed.

Prognosis of resectable colorectal liver metastases after surgery associated with pathological features of primary tumor.

Surgery is an important means for patients with colorectal liver metastases (CRLM) to improve their long-term survival, and accurate screening of high-risk factors is crucial to guiding postoperative monitoring and treatment. With this in mind, the aim of this study was to investigate the expression levels and prognostic roles of Mismatch Repair (MMR), Ki67, and Lymphovascular invasion(LVI) in the tumor tissues of colorectal of CRLM. 85 Patients with CRLM who received surgical treatment for liver metastases after colorectal cancer resection from June, 2017 and Jan, 2020 were included in this study. Independent risk factors affecting the survival of patients with CRLM were investigated using a Cox regression model and the Kaplan-Meier method, and a nomogram for predicting the OS of patients with CRLM was established according to a Cox multivariate regression model. Calibration plots and Kaplan-Meier curves were used to assess the performance of the nomogram. The median survival time was 39 months (95% CI: 32.05-45.950), and MMR, Ki67 and LVI were significantly correlated with prognosis. Univariate analysis indicated that larger metastasis size (p=0.028), more than one liver metastases (p=0.001),higher serum CA199 (p<0.001), N1-2 stage (p<0.001), the presence of LVI (p=0.001), higher Ki67 (p<0.001), and pMMR predicted worse OS. In addition, synchronous liver metastasis (p = 0.008), larger metastasis size (p=0.02), more than one liver metastases (p<0.001),higher serum CA199 (p<0.001), the presence of LVI (p=0.001), nerve invasion (p=0.042) higher Ki67 (p=0.014), and pMMR (p=0.038) were each associated with worse DFS. Multivariate analysis indicated that higher serum CA199 (HR = 2.275, 95%CI: 1.302-3.975 p=0.004), N1-2 stage(HR = 2.232, 95%CI: 1.239-4.020 p=0.008), the presence of LVI (HR = 1.793, 95%CI: 1.030-3.121 p=0.039), higher Ki67 (HR = 2.700, 95%CI: 1.388-5.253\ p=0.003), and pMMR (HR = 2.213, 95%CI: 1.181-4.993 p=0.046) all predicted worse OS. Finally, synchronous liver metastasis (HR = 2.059, 95%CI: 1.087-3.901 p=0.027), more than one liver metastases ((HR =2.025, 95%CI: 1.120-3.662 p=0.020),higher serum CA199 (HR =2.914, 95%CI: 1.497-5.674 p=0.002), present LVI (HR = 2.055, 95%CI: 1.183-4.299 p=0.001), higher Ki67 (HR = 3.190, 95%CI: 1.648-6.175 p=0.001) and pMMR(HR = 1.676, 95%CI: 1.772-3.637 p=0.047) predicted worse DFS, and the nomogram achieved an effective level of predictive ability. This study showed that MMR, Ki67, and Lymphovascular invasion were independent risk factors for the postoperative survival of CRLM patients, and a nomogram model was constructed to predict the OS of these patients after liver metastasis surgery. These results can help surgeons and patients to develop more accurate and individualized follow-up strategies and treatment plans after this surgery.

Perianal Basal Cell Carcinoma-A Systematic Review and Meta-Analysis of Real-World Data.

(1) Background: BCC is a sporadic disease that develops in areas of the skin not exposed to the sun. Perianal BCC, which occurs in the anorectal region, accounts for less than 0.2% of all BCC cases. There have been only a few reported cases of the disease, with fewer than 200 cases reported in total. Given the diagnostic challenges and potential for misdiagnosis, we conducted a systematic review of perianal basal cell carcinoma using real-world data to provide comprehensive and detailed information on the disease. (2) Methods: The study was reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2020. Patients' clinical pathologic features, tumor characteristics, treatment modalities, and outcomes were presented. (3) Results: The results of 41 studies involving 140 patients were analyzed. The most common symptoms reported by patients at presentation were anorectal bleeding, pain, and pruritus. Ulceration was the most frequently observed tumor characteristic. The majority of patients underwent local excision as their primary treatment, with only eight patients experiencing a recurrence. Our analysis did not reveal any statistically significant differences in the outcomes of different treatment modalities. (4) Conclusions: Identifying perianal BCC poses a significant challenge as it closely resembles other anal diseases, thereby making it difficult to differentiate between the different conditions. However, a wide local excision with clear margins is considered an effective treatment option for most patients. Alternative treatments, such as radiotherapy, may be recommended for patients who are unable to undergo surgery.

Pathologic characteristics of somatotroph pituitary tumors - an observational single-center study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Clinical and pathological characteristics of extra-cranial germ cell tumors: A 30-year single-center experience in Saudi Arabia.

To investigate the clinical and pathological characteristics of extracranial germ cell tumors (GCTs) in children aged 0-168 months treated at the National Guard Hospital, Jeddah, Saudi Arabia from 1990 to 2020. In this retrospective analysis, the data for all cases of GCTs were collected from 1990 to 2020. Statistical analyses were carried out using JMP software. The data was divided into 4 main categories: demographics, pathological/clinical features, recurrence, treatment and outcome. The study included 50 patients, with a mean age at diagnosis of 56.52 months. The median follow-up duration was 30 months. Most tumors were in the gonads, and among the extragonadal tumors, the sacro-coccyx was the most frequent site of the disease.The most common histological subtype of GCTs is yolk sac tumor, accounting for 28% of cases. Of the 50 patients, 46% received chemotherapy, and 54% underwent surgery without chemotherapy. Ten (20%) patients experienced recurrence after treatment. At the last follow-up, 96% of the patients were alive, and only 2 of the patients died due to advanced disease. Our findings were comparable to international data, but improvement in surveillance is required for long-term survivors.

Triple Negatif Meme Kanseri Hastalarında Neoadjuvan Kemoterapiye Tam Yanıtı Etkileyen Faktörler

AIM: The triple negative breast cancer is a very aggressive type of breast cancer which constituting approximately 10-15% of all cases. Despite the administration of adjuvant chemotherapy, 5-year disease-free survival rates are lower than other types. Response to treatment may indicate patients' long-term outcome. Several studies are associated with pathological complete response , improved disease-free survival and overall survival . Residual disease after neoadjuvant chemotherapy shows the tumor resistance to treatment. The aim of this study is to explore the relationship between pathological complete response and tumor characteristics.&#x0D; MATERIAL AND METHOD: Data of 53 triple negative breast cancer patients who were operated at one center after neoadjuvant chemotherapy between 2015-2022 were retrospectively analyzed. The data analyzed with descriptive and inferential statistics using SPSS IBM version 25.&#x0D; RESULTS: In the evaluation of 53 patients between the ages of 28 and 81 (mean: 50.7), pathological complete response was obtained in 21 of the patients (39.6 %), while 32 (60.4 %) were found to have an incomplete response or no response. Absence of axillary lymph node metastasis before neoadjuvant chemotherapy, high Ki-67 proliferation index and absence of extracapsular invasion in metastatic LN were associated with pathological complete response; Other clinicopathologic parameters were found to have no effect on the results.&#x0D; DISCUSSION: Patients with a high Ki-67 proliferation index and no axillary involvement are more likely to have a pathological complete response after neoadjuvant chemotherapy.&#x0D; CONCLUSION: It can be predicted that the prognosis may be better in patients with high Ki-67 proliferastion index and no axillary involvement .

Clinical, Radiological and Pathological Features of Desmoid Tumor of the Breast: Case Report

Clinical, Radiological and Pathological Features of Desmoid Tumor of the Breast: Case Report

Zn2+-interference and H2S-mediated gas therapy based on ZnS-tannic acid nanoparticles synergistic enhancement of cell apoptosis for specific treatment of prostate cancer

Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.

Abstract 3296: A urine-based DNA methylation marker test to detect upper tract urothelial carcinoma: a prospective pilot study

Abstract Objectives: Upper tract urothelial carcinoma (UTUC) is an uncommon, yet lethal tumor of the urinary tract. Diagnosis and preoperative risk stratification of these patients present distinct challenges given the limitations of current available diagnostic tools, including endoscopic biopsy and imaging. Herein, we explore the feasibility and clinical performance of a urine-based epigenetic assay in the diagnosis of patients with UTUC. Methods: Under an institutional review board-approved protocol, voided urine samples were prospectively collected using the Bladder CARE Urine Collection Kit (Pangea Laboratory LLC, CA, USA) from primary UTUC patients before any genitourinary manipulation between November 2019 and March 2022. All patients were confirmed to have UTUC in the final specimen. A 1:1 age/sex-matched group of cancer-free healthy donors (control group) was also included in the study. “Healthy” status was based on self-reporting and defined as no history of any type of tumor. Urine samples were analyzed with Bladder CARE, a urine-based test that measures the methylation level of 3 urothelial cancer-specific biomarkers (TRNA-Cys, SIM2, and NKX1-1) and two internal control loci using methylation-sensitive restriction enzymes coupled with qPCR. Results were reported as Bladder CARE Index (BCI) score and categorized as “positive” (BCI &amp;gt; 5), “high risk” (2.5 &amp;lt; BCI ≤ 5) or “negative” (BCI ≤ 2.5). Association between BCI score and category, and clinical and pathological findings was assessed. Results: A total of 50 patients (40 males and 10 females) with a median age of 72 (64-79) years were included in the final analysis. Six patients received neoadjuvant chemotherapy. Surgical procedures included RNU (n=40), ureterectomy (n=7), and URS (n=3). All patients who underwent URS were confirmed to have UTUC through biopsy. Among UTUC patients, Bladder CARE test resulted positive in 47, high-risk in 1, and negative in 2 patients. Comparing Bladder CARE test results with tumor pathologic features demonstrated a statistically significant correlation between BCI values and tumor size (p = 0.009). UTUC patients had significantly higher BCI values compared to the controls (mean BCI 189.3 vs. 1.6, respectively; p &amp;lt; 0.0001). ROC curve showed an AUC of 0.9662 (95% CI = 0.9296-1). Sensitivity, specificity, PPV, and NPV of Bladder CARE to detect UTUC were 96%, 88%, 88.9%, and 95.7%, respectively. In comparison, the sensitivity of urine cytology in our cohort was 37%. Conclusions: In this prospective pilot study, the proposed urine-based epigenetic test (Bladder CARE) showed high sensitivity and negative predictive value in the diagnosis of patients with UTUC. In addition, the sensitivity of this test was exceedingly higher than the standard urine cytology. A larger sample size study to validate the accuracy of this test is the next step. Citation Format: Paolo Piatti, Alireza Ghoreifi, Sanam Seyedian, Yap Ching Chew, Benjamin Jara, Lucy Sanossian, Jeffrey Bhasin, Michael Basin, Taikun Yamada, Gerhard Fuchs, Sumeet Bhanvadia, Rene Sotelo, Andrew Hung, Monish Aron, Mihir Desai, Inderbir Gill, Siamak Daneshmand, Gangning Liang, Hooman Djaladat. A urine-based DNA methylation marker test to detect upper tract urothelial carcinoma: a prospective pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3296.

Dermatofibrosarcoma protuberans of the scalp: Surgical management in a multicentric series of 11 cases and systematic review of the literature

BackgroundDermatofibrosarcoma protuberans is a rare, slow-growing soft-tissue malignancy originating in the dermis that is characterized by an infiltrating growth pattern with a marked tendency of local recurrence. Complete surgical resection with pathological margin clearance must be achieved to reduce the risk of tumor recurrence. Resulting defects often require extensive reconstructive procedures. Dermatofibrosarcoma protuberans of the scalp poses particular challenges owing to the proximity to the face and brain. This study aims to evaluate treatment options and proposes an algorithm for management of scalp dermatofibrosarcoma protuberans based on a multicentric case series and systematic review of the literature. MethodsA retrospective multicentric chart analysis of 11 patients with scalp dermatofibrosarcoma protuberans who presented within the last 20 years was performed regarding demographic data, pathological tumor characteristics, and surgical management (resection and reconstruction). Additionally, a further 42 patients (44 cases) were identified through a systematic Preferred Reporting Systems for Systematic Reviews and Meta-Analysis–based review of the literature searching the Medline and Embase databases. ResultsIn total, 30 cases were classified as primary and 20 cases as recurring scalp dermatofibrosarcoma protuberans (data from 5 cases were missing). The median tumor size was 24 cm2 (interquartile range 7.8–64), and the median defect size was 55.8 cm2 (interquartile range 48–112). Recurring scalp dermatofibrosarcoma protuberans was more often associated with invasion of deeper layers and required more extensive tumor resection to achieve negative margins. Within the subgroup that was managed with peripheral and deep en face margin assessment, no recurrence was observed. Most patients required local (41. 8%) or free flap (27.8%) reconstruction after dermatofibrosarcoma protuberans resection. ConclusionWhenever possible, peripheral and deep en face margin assessment–based techniques should be preferred for resection of scalp dermatofibrosarcoma protuberans because they provide superior oncological safety while preserving uninvolved tissue. Patients with locally advanced and recurring scalp dermatofibrosarcoma protuberans often require multidisciplinary treatment including neurosurgery, radiotherapy, and microvascular reconstructive surgery and should be referred to a specialized center.

Genomic Profiling of the Craniofacial Ossifying Fibroma by Next-Generation Sequencing.

Ossifying fibroma (OF) of the craniofacial skeleton is a fibro-osseous lesion characterized by various patterns of bone formation in a cellular fibroblastic stroma. The molecular landscape of OF remains mostly unknown. There are a few known pathogenic abnormalities in OF, including HRPT2 mutations in conventional OF and SATB2 translocations in juvenile psammomatoid OF. On the other hand, conflicting reports exist regarding MDM2 gene amplification and chromosomal copy number alterations (CNA) in OF. Surgically removed biopsies and curettage specimens from OF patients were obtained. Clinical, radiographic, and pathologic features of tumors were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded blocks of tumor tissue. Capture-based DNA next-generation sequencing targeting the coding regions 529 cancer genes and select introns was performed. We identified 17 OF cases from 8 male and 8 female patients with mean age of 22years (range 1-58years). Nine case occurred in the gnathic bones and 8 in the extragnathic craniofacial bones. These cases included 3 juvenile psammomatoid OF, 6 conventional OF and 8 juvenile trabecular OF. Large-scale CNAs were present in 6 of 17 cases. Seven cases (41%) had focal amplifications including FOSB (n = 2, 11%), FOS (n = 4, 23%), COL1A1 (n = 4, 23%) and TBX3 (n = 5, 29%). Three cases (17%) had pathogenic CDC73 mutations. No cases showed focal MDM2 amplification. Here, we provided a comprehensive molecular characterization of OF that reveals a heterogeneous genetic profile with occasional large-scale CNAs (n = 6, 35%). FOS, FOSB, and TBX3 genes that regulate AP-1 transcriptional complex are frequently altered in OF (n = 7, 41%), chiefly in juvenile trabecular OF. These genes encode transcription factors that act as downstream effectors of the MAP kinase signaling pathway. MDM2 amplification is an exceedingly rare event in OF, if present at all, so identification of this event should continue to raise concern for low-grade gnathic osteosarcoma. In summary, our findings suggest that OF represents a heterogeneous group of tumors at the genetic level but dysregulation of the AP-1 pathway may play a role in pathogenesis of juvenile trabecular OF.

Ultrasound features for prediction of long-term outcomes of women with primary breast cancer

Some women die despite the favorable prognosis of small breast cancers. Breast ultrasound features may reflect pathological and biological characteristics of a breast tumor. This study aimed to explore whether ultrasound features could identify small breast cancers with poor outcomes. This retrospective study examined confirmed breast cancers with a size of <20mm diagnosed in our hospital between 02/2008 and 08/2019. Clinicopathological and ultrasound features were compared between alive and deceased breast cancer patients. Survival was analyzed using the Kaplan-Meier curves. Multivariable Cox proportional hazards models were used to examine the factors associated with breast cancer-specific survival (BCSS) and disease-free survival (DFS). Among the 790 patients, the median follow-up was 3.5 years. The deceased group showed higher frequencies of spiculated (36.7% vs. 11.2%, P<0.001), anti-parallel orientation (43.3% vs. 15.4%, P<0.001), and spiculated morphology combined with anti-parallel orientation (30.0% vs. 2.4%, P<0.001). Among 27 patients with spiculated morphology and anti-parallel orientation, nine cancer-specific deaths and 11 recurrences occurred, for a 5-year BCSS of 77.8% and DFS of 66.7%, while 21 breast-cancer deaths and 41 recurrences occurred among the remaining patients with higher 5-year BCSS (97.8%, P<0.001) and DFS (95.4%, P<0.001). Spiculated and anti-parallel orientation (HR=7.45, 95%CI: 3.26-17.00; HR=6.42, 95%CI: 3.19-12.93), age ≥55 years (HR=5.94, 95%CI: 2.24-15.72; HR=1.98, 95%CI: 1.11-3.54), and lymph nodes metastasis (HR=3.99, 95%CI: 1.89-8.43; HR=2.99, 95%CI: 1.71-5.23) were independently associated with poor BCSS and DFS. Spiculated and anti-parallel orientation at ultrasound are associated with poor BCSS and DFS in patients with primary breast cancer <20mm.

Serum CA724 has no diagnostic value for gastrointestinal tumors.

This study aimed to explore the predictive values of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 199, CA125 and CA724 in the diagnosis of gastrointestinal tumors. Among patients treated for gastrointestinal tumors at the First Affiliated Hospital of Wannan Medical College between December 2020 and March 2022, 572 patients were reviewed as the tumor group, and 700 healthy subjects from the physical examination center of the same hospital were reviewed as the control group. We evaluated the correlation between serum CEA, CA199, CA125, CA724 levels and pathological features in 572 patients with gastrointestinal tumors.The levels of serum CEA, CA199, CA125 and CA724 were compared between the two groups, and the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic efficacy of these markers alone and in combination. Serum CEA level was correlated with tumor stage and metastasis, and CA199 was correlated with tumor stage, lymph node involvement and metastasis. CA125 and CA724 have no correlation with tumor pathological features. The levels of serum CEA, CA199 and CA125 were significantly increased in the tumor group compared with the control group, while serum CA724 levels did not significantly differ between groups (p > 0.05). In addition, in patients with gastric cancer (GC), esophageal cancer (EC), pancreatic cancer (PC), gallbladder cancer (GBC) or colorectal cancer (CRC), the serum CEA, CA199 and CA125 levels were significantly higher than those in the control group (p < 0.05). However, serum CA724 levels were increased only in CRC patients (p < 0.05). ROC curve evaluation results showed that while CA199, CA125 and CA724 alone had poor diagnostic efficacy in the tumor group, CEA was better. Specifically, CEA had better diagnostic efficacy in GC, PC, GBC and CRC; additionally, CA199 and CA125 had better diagnostic efficacy in PC. However, CA724 showed no diagnostic value in the tumor group and the single gastrointestinal tumor group. For diagnosis with multiple-marker combinations, CEA + CA199 + CA125 had the best diagnostic performance (AUC = 0.776, AUC = 0.650, AUC = 0.896, AUC = 0.840, AUC = 0.793) in the GC, EC, PC, GBC and CRC groups, and the sensitivity of multiple-marker combined detection was better than that of single-marker detection. Serum CA724 has no diagnostic value for gastrointestinal tumors, and it cannot evaluate the pathological status of tumors. Serum CEA has excellent diagnostic efficacy in GC, PC, GBC and CRC, and its expression level is related to tumor stage and metastasis. Additionally, CA199 and CA125 have good diagnostic efficacy in PC. Among them, CA199 level was related to tumor stage, lymph node involvement and metastasis, and CA125 level was not related to pathological status. In addition, the multiple-marker combination CEA + CA199 + CA125 has the best diagnostic efficacy in GC, EC, PC, GBC and CRC.

The relationship between Ki-67 expression and imaging signs and pathological features in GISTs.

To investigate the correlations between the Ki-67 index and plain-scan computerized tomography (CT) signs and pathological features of gastrointestinal stromal tumor (GIST) tissue. Data from 186 patients with GIST diagnosed by pathology and immunohistochemistry (IHC) in Peking University First Hospital from May 2016 to May 2022 were analyzed. The patients were divided into two groups: Ki-67 ≤5% and >5%. Correlation analysis, univariate and multivariate Logistic regression analysis were used to explore the correlations between CT signs, pathological features, and Ki-67 expression. Univariate indicators correlated with the Ki-67 index were mitotic count, pathological grade, tumor hemorrhage, tumor necrosis, tumor size, and tumor density. Multivariate Logistic regression indicated that the mitotic count [odds ratio (OR) 10.222, 95% confidence interval (CI) 4.312-31.039], pathological grade (OR 2.139, 95% CI 1.397-3.350), and tumor size (OR 1.096, 95% CI 1.020-1.190) were independently associated with the Ki-67 expression level. The concordance indexes (C-index) for the pathological features and CT signs models were 0.876 (95% CI 0.822-0.929) and 0.697 (95% CI 0.620-0.774), respectively, with positive predictive values of 93.62% and 58.11% and negative predictive values of 81.29% and 75.89%, respectively. After internal verification by the Bootstrap method, the fitting degree of the pathological features model was found to be better than that of the CT signs model. Mitotic count, pathological risk grading, and tumor size are independent risk factors correlating with high Ki-67 index. These results indicate that the Ki-67 index reflects tumor malignancy and can predict recurrence and metastasis of GIST.

Clinical, pathologic, and immunohistochemical features of pituitary tumors in 4 chinchillas.

Pituitary tumors are rare in chinchillas. This report describes the clinical, gross, histologic, and immunohistochemical characteristics of pituitary tumors in 4 chinchillas. The affected chinchillas were females between 4 and 18 years of age. Clinically, neurologic signs were most commonly reported and included depression, obtundation, seizure, head-pressing, ataxia, and possible blindness. Computed tomography scanning of 2 chinchillas revealed solitary intracranial extra-axial masses in the region of the pituitary gland. Two pituitary tumors were confined to the pars distalis; the other 2 invaded the brain. Based on their microscopic appearances and lack of distant metastases, all 4 tumors were diagnosed as pituitary adenomas. Immunohistochemically, all pituitary adenomas were weakly to strongly positive for growth hormone, most consistent with the diagnosis of somatotropic pituitary adenomas. To the authors' knowledge, this is the first detailed report of the clinical, pathologic, and immunohistochemical features of pituitary tumors in chinchillas.

Depth of Invasion, Lymphovascular Invasion, and Perineural Invasion as Predictors of Neck Node Metastasis in Early Oral Cavity Cancers.

The present study examines the role of demographic and pathological features of primary tumours in predicting neck metastasis in early oral cavity cancers, which has been a matter of debate. A single-centre, retrospective, institution review was conducted of all the patients presented to our centre from January 2014 to December 2021. Patient characteristics were compared between the two lymph node groups (lymph node positive and lymph node negative) and significant prognostic factors were determined. A total of 462 oral squamous cell carcinoma (OSCC) patients were included, 407 male and 55 female. Tobacco chewing (59.2%) was a major habit with buccal mucosa (49.5%) and tongue (44.8%) as primary sites. The majority of the patient's histology was of SCC (96.8%) with grade II (moderately differentiated, 74.5%). Univariate logistic regression analysis to predict lymph node metastasis showed pT size (< 0.001), LVI (< 0.001), and PNI (< 0.001) as significant tumor characteristics. On multivariate, pT size (OR-1.58, P - 0.0001) and LVI (OR-19.70, P - 0.0001) were reported to be statistically significant to predict lymph node metastasis. Reporting and studying the clinico-pathological features of primary tumors can give vital information in predicting the neck node metastasis in OSCC patients.

Loss of p53 Concurrent with RAS and TERT Activation Induces Glioma Formation.

There is an ongoing debate regarding whether gliomas originate due to functional or genetic changes in neural stem cells (NSCs). Genetic engineering has made it possible to use NSCs to establish glioma models with the pathological features of human tumors. Here, we found that RAS, TERT, and p53 mutations or abnormal expression were associated with the occurrence of glioma in the mouse tumor transplantation model. Moreover, EZH2 palmitoylation mediated by ZDHHC5 played a significant role in this malignant transformation. EZH2 palmitoylation activates H3K27me3, which in turn decreases miR-1275, increases glial fibrillary acidic protein (GFAP) expression, and weakens the binding of DNA methyltransferase 3A (DNMT3A) to the OCT4 promoter region. Thus, these findings are significant because RAS, TERT, and p53 oncogenes in human neural stem cells are conducive to a fully malignant and rapid transformation, suggesting that gene changes and specific combinations of susceptible cell types are important factors in determining the occurrence of gliomas.

Abstract P1-13-19: ESAM reduces anti-HER2 therapy sensitivity by activating mTOR pathway in HER2 positive breast cancer

Abstract Background: Trastuzumab combined with pertuzumab is the main therapy for HER2 positive breast cancer, but poor patient response due to drug resistance remains a clinical challenge. Organoids derived from tumor patients can highly maintain the heterogeneity of the original tumor, and have been used in drug sensitivity testing and new drug development. To screen for genes that associated with trastuzumab or pertuzumab drug resistance, this study used HER2-positive breast cancer organoids to establish a model of trastuzumab combined with pertuzumab and conducted high-throughput sequencing to screen the differential genes. We carried out further research to explore the effect of ESAM on drug sensitivity of HER2-targeted therapy and clarify the specific regulatory mechanisms and potential therapeutic targets of ESAM. Method: 8 HER2 positive breast cancer organoids were cultured. Immunohistochemistry, hematoxylin-eosin staining and Immunofluorescence were performed to identify the consistency between organoids and primitive tumors. According to drug sensitivity results of organoids to trastuzumab combined with pertuzumab, organoids were divided into a relatively sensitive group and a relatively insensitive group. Trastuzumab combined with pertuzumab was regularly used to stimulate the two groups. After 3 cycles, high-throughput transcriptome sequencing was used to evaluate their gene expression to find a gene responsible for trastuzumab and pertuzumab resistance. METABRIC and our center database were used to determine the prognostic value of ESAM. ESAM overexpression and knockdown stably transfected cell lines were constructed in SK-BR-3 and BT474 breast cancer cell lines by lentivirus. Colony formation assay, CCK-8 assay, organoid model and mouse xenograft model were conducted to examine the influence of ESAM on proliferation and trastuzumab or pertuzumab sensitization in vitro and in vivo. RNA-seq and GSEA analysis were performed to investigate the downstream pathways of ESAM. Western blot was used to confirm the relationship between ESAM and mTOR pathway. Small interfering RNA and mTOR/PI3K pathway inhibitors were used to confirm the function of mTOR in ESAM-induced drug resistance of trastuzumab. Results: HER2 positive breast cancer organoids can maintain the pathological characteristics of primitive tumors. The results of high-throughput transcriptome show that ESAM is significantly up-regulated in the relatively insensitive group compared to the relatively sensitive group. METABRIC and our center database suggest that high ESAM mRNA expression was associated with poor OS, RFS, DFS and PFS of HER2-positive breast cancer patients. CCK-8 and cell colony formation assay confirm that ESAM can promote the proliferation of HER2-positive breast cancer cells and inhibit the drug sensitivity of HER2-positive breast cancer cells to trastuzumab and pertuzumab. GSEA analysis shows high ESAM can activate mTORC1 signaling pathway. Western blotting analysis proves the expression of ESAM is positively correlated with mTOR pathway. Inhibition of mTOR pathway in ESAM overexpression cells can suppress ESAM-mediated proliferation and reverse the drug sensitivity of cells to trastuzumab and pertuzumab. In vivo, overexpression of ESAM can promote the proliferation of mouse mammary tumors and reduce the sensitivity of mouse mammary tumors to trastuzumab, combined use of PI3K inhibitor could reverse drug sensitivity of mouse mammary tumors to trastuzumab. Conclusion: High ESAM expression is associated with poor prognosis in patients with HER2 positive breast cancer. ESAM can activate mTOR pathway, promote cell proliferation and reduce the sensitivity of HER2 positive breast cancer cells to trastuzumab and pertuzumab, which can be inhibited by the application of PI3K/mTOR inhibitors. Keywords: ESAM; HER2 positive breast cancer; HER2 targeted therapy; mTOR; drug sensitivity. Citation Format: Jiong Wu, Xujie Zhou, Yayun Chi, Jingyan Xue. ESAM reduces anti-HER2 therapy sensitivity by activating mTOR pathway in HER2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-19.

Impact of DNA mismatch repair proteins deficiency on number and ratio of lymph nodal metastases in colorectal adenocarcinoma.

Approximately 15 % of colorectal adenocarcinomas (CRCs) are characterized by an altered expression of DNA mismatch repair (MMR) proteins (i.e. MMR deficiency [MMRd]). Lymph node ratio (LNR) represents one of the most important prognostic markers in non-advanced CRCs. No significant data are available regarding LNR distribution depending on MMR status. The aim of the present work was to compare pathological and clinical characteristics of MMRd tumors versus MMR proficient (MMRp) cases. Particular attention was paid to how these molecular sub-groups relate to the LNR. A mono-Institutional series of 1037 consecutive surgically treated stage I-IV CRCs were retrospectively selected and data were obtained from pathological reports. Cases were characterized for MMR/MSI status by means of immunohistochemistry or for microsatellite instability (MSI) analysis. MMRd/MSI tumors (n=194; 18.7 %) showed significant differences in comparison to MMRp lesions for sex (female prevalence 50.5 % vs 40.7 %; p=0.013), age (74.2 vs 69.2; p<0.001), location (right side; p<0.001), diameter (larger than MMRp; p<0.001), growth pattern (expansive pattern of growth; p<0.001), peri- (p=0.0002) and intra-neoplastic (p=0.0018) inflammatory infiltrate, presence of perineural invasion (p<0.001), stage (lower stage at presentation; p<0.001), grade (higher prevalence of high-grade tumors; p<0.001), and LNR (lower; p<0.001). MMRd/MSI tumors are a distinct molecular CRC subtype characterized by a significantly lower LNR in comparison to MMRp lesions. These data further support the prognostic impact of MMRd/MSI status in early-stage CRCs.