Ki-67 Labeling Index Research Articles

Expression of stathmin in oral squamous cell carcinoma and its correlation with tumour proliferation.

Stathmin is a member of microtubule-associated protein. Inhibition of Stathmin expression can interfere with tumour progression and also alter the sensitivity of tumour cells to microtubule-targeting agents. Thus, it could be a potential therapeutic target for planning new treatment strategies. To study expression of Stathmin in different histological grades of oral squamous cell carcinoma (OSCC) and its correlation with Ki67 index. This study was an observational retrospective and prospective study conducted during a period of two and half years from January 2015 to June 2017 at ESI-PGIMSR Maniktala, Kolkata where 52 cases of OSCC were studied. Haematoxylin and eosin sections were reviewed and representative paraffin blocks were selected. Immunostains were performed using antibody clones for Stathmin and Ki67. For Stathmin scoring, Segersten scoring system was applied. Statistical analysis was done by Graph Pad Prism using Krusher Wallis Test and one-way ANOVA test. Spearman's coefficient was used to establish corelation between Ki 67 and Stathmin overexpression. In this study, it is found that strong Stathmin expression score (4-9) was detected mostly (82.35%) in moderately differentiated (MD) OSCC and poorly differentiated (PD) OSCC (100%), whereas in contrast, 60% of well-differentiated OSCC showed negative-to-weak Stathmin score (1-3). Mean Ki67-labelling index for well-differentiated carcinoma was 32.37%, for moderately differentiated carcinoma was 60.89, and poorly differentiated carcinoma was 86.15%, which demonstrated increased tumour cell proliferation with progression of histological grades of OSCC. Stathmin expression was higher in MD OSCC to PD OSCC compared to well-differentiated carcinoma and its overexpression was significantly correlated with Ki67 index. Thus, Stathmin is overexpressed in higher grades and is correlated with high proliferation of tumour with a potential role as therapeutic target.

Appendiceal Neuroendocrine Tumor Mimicking Acute Appendicitis

Appendiceal carcinoids are the most frequent tumors arising from the appendix, comprising between 32 and 57% of all the appendiceal tumors. The gross appearance of the appendix showed perforation at the tip with 30 ml of peri-appendicular collection. On histopathological examination, carcinoid tumor on the tip of appendix was found with tumor cells arranged in tubules, acini and nests infiltrating the muscularis propria and sub serosa. Perineural and vascular invasion was not seen. Immunohistochemistry for Synaptophysin was positive with Ki-67 labelling index of 2%. We present a case of appendiceal neuroendocrine tumor with the chief complaint of acute appendicitis.

18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Predicts Tumor Immune Microenvironment Function in Early Triple-negative Breast Cancer.

The maximum standardized uptake value (SUVmax) obtained using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is presumed to indicate tumor and active immune cells in the tumor immune microenvironment (TIME) based on their glycolysis activity. Therefore, this study investigated whether the metabolic parameter SUVmax could provide information regarding TIME in triple-negative breast cancer (TNBC) patients. Fifty-four patients with TNBC underwent FDG PET/CT before neoadjuvant chemotherapy. Pretreatment biopsy specimens were pathologically evaluated. Expression statuses of CD8, forkhead box P3 (FOXP3), programmed cell death-1 (PD-1), and programmed cell death-ligand 1 (PD-L1) were assessed by immunohistochemistry. The relationships between immunological factors, including the tumor-infiltrating lymphocyte (TIL) grade and SUVmax or pathological complete response (pCR), were investigated. CD8, FOXP3, PD-1, and PD-L1 were high in 15 (27.8%), 39 (72.2%), 18 (33.3%), and 26 (48.2%) patients, respectively. SUVmax was significantly correlated with tumor size, Ki-67 labeling index, and CD8/FOXP3 ratio. Multiple linear regression analysis indicated that tumor size and the CD8/FOXP3 ratio predicted SUVmax. Seventeen patients (31.5%) achieved a pCR; TILs, the CD8/FOXP3 ratio, PD-1, and PD-L1 were significantly correlated with pCR rate. Multivariate analysis indicated that the CD8/FOXP3 ratio was the only independent predictive factor for pCR. SUVmax could provide metabolic information regarding TIME for TNBC patients and might be beneficial for formulating a treatment strategy and predicting pCR after neoadjuvant chemotherapy.

Correlation of MTAP immunohistochemical deficiency with CDKN2A homozygous deletion and clinicopathological features in pleomorphic xanthoastrocytoma

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor ranging from World Health Organization (WHO) grades 2-3 and can potentially recur and metastasize throughout the central nervous system (CNS). Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion is a frequent genomic alteration of PXA. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in PXA. Therefore, we performed CDKN2A fluorescence in situ hybridization and MTAP immunohistochemistry on specimens from 23 patients with CNS WHO grades 2 (n = 10) and 3 (n = 13) PXAs, including specimens from primary and recurrent tumors, and determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 30% (3/10) and 76.9% (10/13) of CNS WHO grades 2 and 3 PXAs, respectively. In addition, MTAP loss was inconsistent with CDKN2A homozygous deletion (sensitivity = 86.7%, specificity = 100%). Furthermore, CDKN2A homozygous deletion was correlated with WHO grade (p = 0.026) and the Ki-67 labeling index (p = 0.037). Therefore, MTAP immunostaining can be a suitable surrogate marker for CDKN2A homozygous deletions in PXAs, and CDKN2A homozygous deletions may be an important prognostic factor for PXAs.

Cauda Equina Neuroendocrine Tumors: Distinct Epithelial Neuroendocrine Neoplasms of Spinal Origin.

The tumor formerly known as "cauda equina paraganglioma" was recently renamed as cauda equina neuroendocrine tumor (CENET) based on distinct biological and genetic properties. Nevertheless, it remains insufficiently understood. For this study, we retrieved CENETs (some previously reported), from the pathology files of 3 institutions; we examined their immunohistochemical profile, including common neuroendocrine tumor-associated hormones and transcription factors. We identified 24 CENETs from 7 female and 17 male adult patients, with a median age of 47 years. Six included neurofilament-positive ganglion cells. All tumors tested were positive for INSM1, synaptophysin, chromogranin A, SSTR2, and CD56 as well as at least 1 keratin (AE1/AE3, CAM5.2); CK7 and CK20 were negative. Glial fibrillary acidic protein was negative, except for peripheral nontumoral elements. S100 protein was variable but mainly expressed in scattered sustentacular cells. All but 1 tumor tested were positive for HOXB13; several stained for SATB2, and all tumors were consistently negative for GATA3. All tumors tested were negative for transcription factors found in various other epithelial neuroendocrine neoplasms including TTF1, CDX2, PIT1, TPIT, SF1, and PAX8; staining for T-brachyury was negative. Four of 5 CENETs tested had at least focal tyrosine hydroxylase reactivity. Serotonin expression was detected in all 21 tumors tested; it was diffusely positive in 5 and had variable positivity in the remainder. A few tumors had scattered cells expressing gastrin, calcitonin, pancreatic polypeptide, and peptide YY, while glucagon, adrenocorticotropic hormone, and monoclonal carcinoembryonic antigen were negative. PSAP expression was found focally in 4 of 5 tumors examined. SDHB was consistently intact; ATRX was intact in 14 tumors and showed only focal loss in 3. The median Ki-67 labeling index was 4.5% (range: 1% to 15%). We conclude that CENET represents a distinct neuroendocrine neoplasm; the subset with ganglion cells qualifies for designation as composite gangliocytoma/neuroma-neuroendocrine tumor (CoGNET) as defined in the 2022 WHO classification of neuroendocrine neoplasms. In addition to INSM1, chromogranin, synaptophysin, and keratins, the most characteristic finding is nuclear HOXB13 expression; a subset also express SATB2. Serotonin is the most common hormone expressed. The cytogenesis and pathogenesis of these lesions remains unclear.

Porphyromonas gingivalis-Derived Lipopolysaccharide Promotes Glioma Cell Proliferation and Migration via Activating Akt Signaling Pathways.

Periodontitis is significantly associated with the risk of cancers in the lung and the digestive system. Emerging evidence shows a plausible link between periodontitis and several types of brain diseases. However, the association between periodontal infection and glioma remains unclear. In the cultured GL261 glioma cells, P. gingivalis lipopolysaccharide (LPS) significantly promoted cell proliferation at concentrations ranging from 10 to 1000 ng/mL. It promoted cell migration at a higher concentration (100 and 1000 ng/mL). Additionally, exposure to 100 ng/mL P. gingivalis LPS induced a significant increase in the expression of TNF-α, TGF-β, MMP2, and MMP9, as well as the phosphorylation level of Akt at Ser473. These changes induced by P. gingivalis LPS were significantly antagonized by the Akt inhibitor. Furthermore, a total of 48 patients with brain tumors were enrolled to investigate their periodontal status before receiving tumor management. Poor periodontal status [probing depth (PD) ≥ 6 mm and attachment loss (AL) >5 mm] was found in 42.9% (9/21) of patients with glioma, which was significantly higher than that in patients with benign tumors and the relevant data in the 4th National Oral Health Survey in China. The glioma patients with both AL > 5 mm and PD ≥ 6 mm had a higher ki-67 labeling index than those with AL ≤ 5 mm or PD < 6 mm. These findings support the association between periodontal infection and glioma progression.

Grading of gliomas using 3D CEST imaging with compressed sensing and sensitivity encoding

PurposeWe evaluated the usefulness of three-dimensional (3D) chemical exchange saturation transfer (CEST) imaging with compressed sensing and sensitivity encoding (CS-SENSE) for differentiating low-grade gliomas (LGGs) from high-grade gliomas (HGGs). MethodsWe evaluated 28 patients (mean age 51.0 ± 13.9 years, 13 males, 15 females) including 12 with LGGs and 16 with HGGs, all acquired using a 3 T magnetic resonance (MR) scanner. Nine slices were acquired for 3D CEST imaging, and one slice was acquired for two-dimensional (2D) CEST imaging. Two radiological technologists each drew a region of interest (ROI) surrounding the high-signal-intensity area(s) on the fluid-attenuated inversion recovery image of each patient. We compared the magnetization transfer ratio asymmetry (MTRasym) at 3.5 ppm in the tumors among the (i) single-slice 2D CEST imaging (“2D”), (ii) all tumor slices of the 3D CEST imaging (3Dall), and (iii) a representative tumor slice of 3D CEST imaging (maximum signal intensity [3Dmax]). The relationship between the MTRasym at 3.5 ppm values measured by these three methods and the Ki-67 labeling index (LI) of the tumors was assessed. Diagnostic performance was evaluated with a receiver operating characteristic analysis. The Ki-67LI and MTRasym at 3.5 ppm values were compared between the LGGs and HGGs. ResultsA moderate positive correlation between the MTRasym at 3.5 ppm and the Ki-67LI was observed with all three methods. All methods proved a significantly larger MTRasym at 3.5 ppm for the HGGs compared to the LGGs. All methods showed equivalent diagnostic performance. The signal intensity varied depending on the slice position in each case. ConclusionsThe 3D CEST imaging provided the MTRasym at 3.5 ppm for each slice cross-section; its diagnostic performance was also equivalent to that of 2D CEST imaging.

Intratumoral Heterogeneity of Fibrosarcoma Xenograft Models: Whole-Tumor Histogram Analysis of DWI and IVIM

To explore the correlations of histogram parameters from diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with the heterogeneous features in a nude mouse model of fibrosarcoma. A total of 44 fibrosarcoma xenograft models were established by inoculating HT-1080 cells on the right thigh of mice and subjected tumors to DWI and IVIM imaging with 3.0 T MRI. Whole-tumor histogram parameters were calculated on apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Heterogeneous features, including necrosis rate, cell density, Ki-67 labeling index (LI), and microvascular density (MVD) were measured. Intraclass correlation coefficients (ICC), Pearson or Spearman correlation tests, and receiver operating characteristics (ROC) were performed. The 90th percentile, skewness and kurtosis of ADC and D histograms showed correlations with necrosis rate, and the highest correlation coefficient was found for D90th (r=0.485). ADC and D histogram parameters showed correlations with cell density and Ki-67 LI; D90th showed the highest correlation coefficient with cell density (r=-0.504); and Dmedian showed the most significant correlation with Ki-67 LI (r=-0.525). D*skewness, D*kurtosis, D*90th, fmean, and fmedian showed correlations with MVD. ADC90th, ADCskewness, ADCkurtosis, D90th, and Dskewness showed significant differences between the low necrosis and high necrosis groups, and the combination model showed the best diagnostic ability (AUC=0.882), with 97% sensitivity, and 72.7% specificity. Whole-tumor histogram parameters of DWI and IVIM were correlated with heterogeneous features in nude murine models of fibrosarcoma.

CD47 mediates the progression of colorectal cancer by inducing tumor cell apoptosis and angiogenesis.

CD47 is an immunoregulatory protein that is found on the cell surface and plays significant roles in cellular functions such as proliferation, apoptosis, migration, and immune homeostasis. CD47 is overexpressed in various human cancers and is associated with tumor development, progression, and poor prognosis. In this study, we analyzed the expression of CD47 to determine whether it affected the oncogenic behavior of colorectal cancer (CRC) and investigated the prognostic value of CD47 expression in patients with CRC. We investigated 468 patients with CRC who underwent curative surgery and examined the expression of CD47 in tumor and lymph node tissues by performing RT-PCR and immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined via a TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. CD47 expression was increased in human CRC tumors and metastatic lymph nodes compared with normal colorectal mucosa and non-metastatic lymph node tissues. CD47 expression was significantly associated with perineural invasion, lymphovascular invasion, cell differentiation, cancer stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival. The mean apoptotic index and microvessel density value of CD47-positive tumors were significantly higher than those of CD47-negative tumors. However, no significant difference was observed between CD47 expression and Ki-67 labeling index or lymphatic vessel density. These results indicate that CD47 mediated the progression of CRC by inducing tumor cell apoptosis and angiogenesis.

An integrative non-invasive malignant brain tumors classification and Ki-67 labeling index prediction pipeline with radiomics approach

BackgroundThe histological sub-classes of brain tumors and the Ki-67 labeling index (LI) of tumor cells are major factors in the diagnosis, prognosis, and treatment management of patients. Many existing studies primarily focused on the classification of two classes of brain tumors and the Ki-67LI of gliomas. This study aimed to develop a preoperative non-invasive radiomics pipeline based on multiparametric-MRI to classify-three types of brain tumors, glioblastoma (GBM), metastasis (MET) and primary central nervous system lymphoma (PCNSL), and to predict their corresponding Ki-67LI. MethodsIn this retrospective study, 153 patients with malignant brain tumors were involved. The radiomics features were extracted from three types of MRI (T1-weighted imaging (T1WI), fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted imaging (CE-T1WI)) with three masks (tumor core, edema, and whole tumor masks) and selected by a combination of Pearson correlation coefficient (CORR), LASSO, and Max-Relevance and Min-Redundancy (mRMR) filters. The performance of six classifiers was compared and the top three performing classifiers were used to construct the ensemble learning model (ELM). The proposed ELM was evaluated in the training dataset (108 patients) by 5-fold cross-validation and in the test dataset (45 patients) by hold-out. The accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-Score, and the area under the receiver operating characteristic curve (AUC) indicators evaluated the performance of the models. ResultsThe best feature sets and ELM with the optimal performance were selected to construct the tri-categorized brain tumor aided diagnosis model (training dataset AUC: 0.96 (95% CI: 0.93, 0.99); test dataset AUC: 0.93) and Ki-67LI prediction model (training dataset AUC: 0.96 (95% CI: 0.94, 0.98); test dataset AUC: 0.91). The CE-T1WI was the best single modality for all classifiers. Meanwhile, the whole tumor was the most vital mask for the tumor classification and the tumor core was the most vital mask for the Ki-67LI prediction. ConclusionThe developed radiomics models led to the precise preoperative classification of GBM, MET, and PCNSL and the prediction of Ki-67LI, which could be utilized in clinical practice for the treatment planning for brain tumors.

WITHDRAWN: Thoracic spinal metastasis as recurrence of borderline Brenner tumor without local recurrence: A case report

Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2-3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10%]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50-60%]. She received adjuvant radiation of 30Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown. We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence.

Immunohistochemical study of neural stem cell lineage markers in canine brains, gliomas, and a glioma cell line.

Neural stem cells (NSCs) produce neuron intermediate progenitor cells (nIPC), oligodendrocyte precursor cells (OPCs), and immature astrocytes. To confirm NSC lineages in the normal canine brain and the association of these cells with gliomas, an immunohistochemical study was conducted on fetal and adult canine brains, gliomas, and a glioma cell line. In fetal brains, glial fibrillary acidic protein (GFAP)- and nestin-immunolabeled NSC were observed in the ventricular zone, β-3 tubulin- and/or neuronal nuclei (NeuN)-immunolabeled nIPC in the subventricular zone (SVZ), and platelet-derived growth factor receptor-α (PDGFR-α)- and OLIG2-immunolabeled OPC and GFAP- and OLIG2-immunolabeled immature astrocytes in the SVZ and intermediate zone. Ki-67 immunohistochemistry revealed that nIPC exhibited high proliferative activity. Quiescent nIPC and OPC were observed in adult brains. Among 58 glioma cases including 4 low-grade oligodendrogliomas (LGOGs), 48 high-grade oligodendrogliomas (HGOGs), 1 low-grade astrocytoma, and 5 high-grade astrocytomas (HGACs), immunohistochemical analyses revealed that oligodendrogliomas expressed PDGFR-α and OLIG2, whereas astrocytomas expressed GFAP and OLIG2. HGOG showed significantly higher immunohistochemical scores for NeuN and β-3 tubulin than LGOG. The Ki-67 labeling index was high in PDGFR-α and NeuN-immunolabeled tumor cells, and low in β-3 tubulin- and synaptophysin-immunolabeled cells. A HGOG cell line possessed the same immunohistochemical characteristics as HGOG. In this study, glioma cells with the OPC and IPC immunophenotypes had a higher Ki-67 labeling index, indicating their high proliferative activity. Furthermore, high-grade gliomas showed the characteristics of nIPC and neurons, which may suggest the pluripotent NSC lineage nature of these tumors.

NIMG-15. INTEGRATED RADIOGRAPHIC AND PATHOLOGICAL ANALYSIS OF MALIGNANT PERIPHERAL NERVE SHEATH TUMORS (MPNSTS) REVEALS IMAGING CORRELATES OF MOLECULAR ALTERATIONS AND CLINICAL OUTCOME

Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are the most common cause of death in patients with neurofibromatosis type 1 (NF-1) yet non-invasive diagnosis and risk stratification of NF-1-associated peripheral nerve tumors remains challenging. Moreover, the relationship between radiographic features and pathologic measures such as mitotic index and necrosis, or molecular markers of malignant transformation such as H3K27 trimethylation and Schwann cell marker (S100B, SOX10) expression remain unknown. Here, we integrate positron emission tomography (PET) (n=32 studies from 18 patients) and magnetic resonance imaging (MRI) (n=20 studies from 20 patients) with immunohistochemical analysis and clinical follow-up in a total of 20 patients with pathologically confirmed MPNST diagnosis. The median age was 33 years (range 5-74 years), n = 11 were male (55%) and n=13 (65%) harbored a clinical diagnosis of NF-1. Anatomically, n=6 (30%) tumors arose near the spine, n=5 (25%) arose in the extremities, and n=4 (20%) arose in the sacrum. By PET, the average preoperative SUVmax was 8.53 with a trend toward increased SUVmax in Ki-67 high tumors (SUVmax 10.58 vs. 6.47, p=0.08). No significant differences in SUVmax based on H3K27 trimethylation, SOX10, or S100B expression was noted. The appearance of cystic necrosis by MRI was significantly associated with H3K27 trimethylation loss (Chi-square p=0.04) with a trend toward increased KI-67 labeling (43% vs. 24%, p = 0.07), suggesting cystic necrosis identifies aggressive lesions. No other features were correlated with H3K27 trimethylation status or Ki-67 labeling index. With regard to clinical outcome, dichotomized SUVmax identified patient subgroups with significant differences in overall survival (OS), with high SUVmax tumors demonstrating improved survival (median OS: 250 months vs. 60 months, log-rank test p=0.02). Our data support a relationship between radiographic features, histopathologic characteristics and clinical outcomes. Future work will include longitudinal analysis, validation in larger, multi-institutional cohorts and incorporation of radiomic approaches.

Automated Prostate Cancer Identification Facilitates Prognosis Marker Assessment in 11,845 Prostate Cancers Using Artificial Intelligence and BLEACH&STAIN Multiplex Fluorescence Immunohistochemistry

Abstract Introduction/Objective Although most prostate cancers behave in an indolent manner, a small proportion is highly aggressive. To evaluate the patient’s risk, several prognosis parameters, that can be accompanied by a high interobserver variability has been established. A reproducible prognostic evaluation is lacking. Methods/Case Report To enable automated prognosis marker quantification, we have developed and validated a framework for automated prostate cancer detection that comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of BLEACH&STAIN multiplex fluorescence immunohistochemistry (mfIHC). We have used the analysis framework to measure PSA, PSMA, INSM1, AR, Ki-67, CD56, Chromogranin A, Synaptophysin, CD8 in a cohort of 11,845 prostate cancers. Results (if a Case Study enter NA) The Ki-67 labeling index provided the strongest prognostic information among all analyzed prognosis marker in 11,845 successfully analyzed prostate cancers (p<0.001 each). The combined analysis of the Ki67-LI and Gleason grades obtained on identical tissue spots showed that the Ki67-LI added significant additional prognostic information in case of classical ISUP grades (AUC:0.82 [p=0.002]) and quantitative Gleason grades (AUC:0.83 [p=0.018]). Several combinations of these 8 prognosis markers were combined to prognosis scores and used for unsupervised clustering to identify a proportion of prostate cancers with a particularly poor prognosis (p<0.001 each). Conclusion Automated prostate cancer identification enables fully automated prognosis marker assessment in routine clinical practice using deep learning and BLEACH&STAIN mfIHC.

ODP559 The prognostic role of IL-17A-neutrophils crosstalk in triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is characterized by extensive intratumoral heterogeneity. At this juncture, TNBCs are treated with conventional chemotherapy and have few targeted therapies. Due to the presence of increased tumor-infiltrating lymphocytes and immune-checkpoint molecules, TNBCs are considered highly immunogenic. This provides an opportunity to explore various immunotherapeutic options. The immune cells such as Th17 cells or neutrophils (tumor-associated neutrophils; TANs) can secrete a pro-inflammatory cytokine called IL-17A, which is known to be associated with poor outcomes in several cancers. TANs are related to tumor progression and are influenced by certain chemokines. Meanwhile, IL-17A can also regulate chemokine (C-X-C motif) ligand 1 (CXCL1), which is a strong chemoattractant for TANs and can lead to the growth of tumors in breast cancer. However, the significance of IL-17A and its interaction with TANs and CXCL1 has yet not been clearly understood in TNBC. For this purpose, formalin-fixed paraffin-embedded biopsy tissue specimens of 109 Japanese TNBC patients were included in this study. Immunohistochemistry was performed to assess the status of IL-17A, CXCL1, and CD66b (a neutrophil marker) and to understand their correlation among each other, with clinical parameters, and with the outcomes of patients. Also, in vitro studies were performed to evaluate the effect of recombinant IL-17A on TNBC cell lines proliferation, migration, and CXCL1 expression. Clinical results revealed that IL-17A was significantly correlated with CXCL1 and CD66b, which suggested potential crosstalk between them. On the other hand, CXCL1 significantly and CD66b tended to be correlated with tumor size. Also, CD66b was significantly correlated with the Ki-67 labeling index, showing that TANs may have a role in tumor cell proliferation. Kaplan-Meier survival curves showed that high IL-17A was significantly associated with poor disease-free and overall survival, indicating the poor outcome of the TNBC patients. To our great interest, in vitro results revealed that no difference was observed for proliferation or migration of TNBC cell lines (was only observed in the MDA-MB-231 cell line) after treatment with recombinant IL-17A. However, CXCL1 was highly up-regulated in a dose and time-dependent manner after exposure to IL-17A, indicating that IL-17A might be involved in the recruitment of neutrophils through up-regulation of CXCL1. Therefore, we concluded that IL-17A was a poor prognostic factor for TNBC patients, enhancing the chemokine-neutrophil recruitment to the tumor site, leading to tumor progression and aggression. In the future, we intend to explore different pathways for understanding the mechanism of CXCL1 up-regulation by IL-17A. Presentation: No date and time listed

ODP364 Prolactinomas in men: management challenges

Abstract Introduction Prolactinomas are the most common pituitary adenomas (Pas), with an estimated higher prevalence in women. Over 90% of prolactinomas are small, intrasellar tumors that rarely increase in size, but occasionally, these PAs can be aggressive or locally invasive and cause compression of vital structures. Usually, prolactinomas in male patients are large, invasive, but the reasons for the more aggressive course remain poorly understood. Also, male prolactinomas have a lower expression of estrogen receptor alpha (ERα), which is associated with higher proliferation rates, resistance to dopamine agonists and a poor prognosis (1). Objective To investigate the impact of sex-related differences in prolactinomas. Material and Methods We analyzed 76 patients with confirmed diagnosis of prolactinomas. The patient`s information was collected retrospectively between 2018 and 2021. The patients had a mean age of 40,9 years old (range 18-77) and the majority were males (56,75%). We identified 15 patients (11 males, 4 females) with prolactin (PRL) secreting macroadenomas who underwent pituitary surgery (transsphenoidal, ten patients; transcranial five patients, and three of them had two transsphenoidal interventions and one of them had two transcranial interventions), four had also radiotherapy (three patients had high voltage radiation therapy and one had gamma knife radiosurgery). In the group of patients who underwent pituitary surgery, mean pre-operative maximal diameter was 35.65 ± 14.83 mm (6 giant prolactinomas, all of them in males) with mean PRL levels at presentation of 3640 ng/ml (range 560–16000), with significant higher levels observed in male patients. Eleven patients had visual field defects and the same number had panhypopituitarism with hormonal replacement therapy. Only two patients (females) are now normoprolactinemic without treatment with dopamine agonists. Nine tumors were considered invasive, according to Knosp classification (grade 3-4). Two female patients had remission of the disease following surgery. Nine patients had residual tumors after surgery, with controlled PRL secretion under treatment with dopamine agonists. The nuclear positive cells for Ki-67 were quantified by bright field microscopy (magnification x200) using QuantCenter software, its values ranging from 1% to 20%, with a value of 15-20% in the case of a male patient with giant prolactinoma with cavernous sinus invasion. Conclusion Significantly higher prolactin concentrations are observed in men as compared to women, in PRL secreting pituitary adenomas. The reasons for a more aggressive course of prolactinomas in men remain poorly understood, the higher rates of proliferation markers, such as the Ki-67 labeling index or the mitotic count, the low expression of ERα may explain the more aggressive behavior in men. Reference: Maiter D. Prolactinomas in Men. In: Tritos N., Klibanski A. (eds) Prolactin Disorders. Contemporary Endocrinology. Humana, Cham, 2019. Pp 184-204. https://doi.org/10.1007/978-3-030-11836-5_1 Presentation: No date and time listed

ODP021 A Feminizing Adrenocortical Carcinoma Presenting with Marie-Antoinette Syndrome

Abstract Introduction Adrenocortical carcinomas (ACCs) are rare and aggressive malignant tumors often with an unfavorable prognosis accounting for 0. 05-0.2% of all cancers. ACCs can be separated into 2 groups: Functioning (hormone-producing) and non-functioning tumors. About 60% of ACCs synthesize hormones. Hormone-secreting ACCs most commonly cause virilization or Cushing's syndrome. On very rare occasions, ACCs can lead to feminization in male subjects. Clinical manifestations are gynecomastia and/or hypogonadism. Here, we present a case of an estradiol-secreting adrenal cortical carcinoma. Case presentation A 58-year-old male presented with patchy hair loss, change in hair colour to white, loss of body hair and eyebrows, and breast tenderness. Hormone testing revealed significantly elevated estradiol came 582 pmol/L [NR<190] with a very low testosterone of 1.6 nmol/L [NR10-30], low FSH 0.1 mIU/mL [NR 0.95-11.5] and LH of 0.6 mIU/mL [NR1.14-8.75]. A testicular ultrasound was unremarkable. An adrenal MRI revealed an 11 cm heterogeneous right adrenal mass invading the inferior vena cava. FDG PET-CT revealed an intensely metabolically active tumor without any evidence of metastatic disease. The tumor was successfully removed via an open procedure. Histology confirmed an adrenocortical carcinoma with a Weiss score of 8 with a mitotic account of 10/50 HPF and Ki-67 labelling index of 20-25%. There was vascular invasion with large areas of necrosis, ENSAT (European Network for the Study of Adrenal Tumours) stage II. Postoperatively, he made a good clinical recovery and was offered adjuvant Mitotane and EDP (Doxorubicin, Etoposide and Cisplatin) chemotherapy. Due to a significant rise in GGT and platelets, Mitotane had to be stopped temporarily. During the course of his treatment, he developed a hoarse voice and CT neck revealed abnormal thickening of the lateral aspects of the aortic arch suggesting possible tumor recurrence or aortitis. A biopsy was not diagnostic, but did not show any features of malignancy. He completed his five cycles of EDP chemotherapy. Estradiol has remained normal and his hoarse voice improved. Conclusion We describe a rare case of an estradiol-secreting ACC presenting with feminization and Marie-Antoinette syndrome as well as possible paraneoplastic aortitis. Targeted molecular tumor analysis may guide further treatment options and enrolment in clinical trials should be considered. Presentation: No date and time listed

ODP050 Oncocytic Adrenocortical Carcinoma Presenting with Hematuria

Abstract Introduction Adrenocortical carcinoma (ACC) is rare and aggressive endocrine tumor. It is commonly noticed due to symptoms of hormone excess, mass-effect, or incidentalomas. Different histological variants are noted, which include: oncocytic, myxoid, sarcomatoid, and the conventional subtype. The oncocytic variant is usually seen on the left side, and usually presents with symptoms of mass-effect. Only around 17% were noted to be functional. We present an interesting case of ACC (oncocytic type) which presented with hematuria. Case Presentation 70-year-old female with a history of morbid obesity, hypertension, anxiety, GERD, tubular adenoma, hyperlipidemia, and lumbar radiculopathy came in to see her primary care for hematuria and back pain. She has a long-standing history of back pain, for which she has had an EMG, which showed mild axonal polyneuropathy and bilateral L5 radiculopathy. Apart from hematuria, she denies any other urinary complaints. Additionally, she denied any fever, chills, nausea, abdominal pain, sweating, tremor, headache, palpitations, easy bruising, fractures, muscle weakness, hirsutism, or changes in her weight. She has a family history of pancreatic cancer and is currently retired, and denies alcohol, tobacco, or recreational drug use. A KUB X-ray was ordered which showed calcification in the left upper quadrant, concerning for a splenic artery aneurysm; this led to a CTA abdomen, which showed a large 7.2 cm heterogenous enhancing solid left adrenal mass, concerning for primary adrenal carcinoma, which was new compared to imaging 2 years ago. Also seen was a 0.7 cm enhancing right hepatic lobe lesion, along with a 1.5 cm splenic artery aneurysm. Following this, an abdomen MRI with contrast showed a 7×7×7 cm solid heterogeneously enhancing left upper quadrant mass beside the left adrenal gland and pancreas. Subsequently, a CT guided needle biopsy was done, which revealed scant adrenal tissue. PET scan showed a hypermetabolic mass, arising from the left adrenal, consistent with adrenal carcinoma. At this point, an endocrinology referral was placed, and other lab work including 24-hour urine free cortisol, DHEA-S, 24-hour urine metanephrine, and aldosterone/renin ratio was done. DHEA-S level was elevated at 264 mcg/dl (12-133). She was then transferred to a tertiary care facility, where she underwent a left adrenalectomy, para-aortic lymphadenectomy, nephrectomy, splenectomy, and distal pancreatectomy. Pathology confirmed adrenal cortical carcinoma (oncocytic type), with negative margins, Ki-67 labelling index of 25%, and no lymphovascular invasion, pT2pNO. She was then discharged home with visiting nurses. Conclusion Oncocytic ACC is an infrequent tumor, which presents with symptoms of mass effect, and definitive diagnosis requires histopathological assessment. The Lin–Weiss–Bisceglia (LWB) system and Helsinki score help establish malignant potential. Fortunately, it has a decreased tendency to metastasize and a better prognosis than other ACC subtypes. Further studies to understand oncocytic ACC are needed. Presentation: No date and time listed

Establishment of a nomogram for predicting lymph node metastasis in patients with early gastric cancer after endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) has been accepted as the standard treatment for the appropriate indication of early gastric cancer (EGC). Determining the risk of lymph node metastasis (LNM) is critical for the following treatment selection after ESD. This study aimed to develop a predictive model to quantify the probability of LNM in EGC to help minimize the invasive procedures. A total of 952 patients with EGC who underwent radical gastrectomy were retrospectively reviewed. LASSO regression was used to help screen the potential risk factors. Multivariate logistic regression was used to establish a predictive nomogram, which was subjected to discrimination and calibration evaluation, bootstrapping internal validation, and decision curve analysis. Results of multivariate analyses revealed that gender, fecal occult blood test, CEA, CA19-9, histologic differentiation grade, lymphovascular invasion, depth of infiltration, and Ki67 labeling index were independent prognostic factors for LNM. The nomogram had good discriminatory performance, with a concordance index of 0.816 (95% CI 0.781-0.853). The validation dataset yielded a corrected concordance index of 0.805 (95% CI 0.770-0.842). High agreements between ideal curves and calibration curves were observed. The nomogram is clinically useful for predicting LNM after ESD in EGC, which is beneficial to identifying patients who are at low risk for LNM and would benefit from avoiding an unnecessary gastrectomy.

Comparison of surgery with or without adjuvant radiotherapy in treating central neurocytoma: a single-center retrospective real-world study.

To investigate the efficacy and safety of adjuvant radiotherapy (RT) in patients with central neurocytoma (CN). The study included 68 patients with CN retrospectively, wasfurther divided into surgery + RT group (31 patients) and surgery alone group (37 patients). Progression-free survival (PFS), overall survival (OS), and adverse reactions (AEs) were compared between the two groups. The median follow-up duration was 82.2 (interquartile range, 64.7-104.5) months. Patients in the surgery + RT group tended to have longer PFS than those in the surgery alone group (5-year PFS rate: 92.7% vs. 86.3%; P = 0.074). There was no significant difference in OS between the two groups (5-year OS rate: 96.8% vs. 94.3%; P = 0.639). Subgroup analysis revealed a significant improvement in PFS in patients receiving RT after surgery in patients who underwent subtotal resection (STR) (P = 0.045). In the overall population, univariate multivariate analysis revealed that gross total resection (GTR) (P = 0.002), tumor location in the unilateral ventricle (P = 0.008), and MIB-1 (Ki-67)labeling index (LI) < 5% (P = 0.009) were favorable independent prognostic factors for PFS. Whereas tumor location in the unilateral ventricle (P = 0.043) was a favorable independent prognostic factor for OS. Moreover, RT patients experienced AEs (Grade 1-2, well-tolerated). Adjuvant RT in the treatment of CNs showed satisfactory safety, and postoperative RT could improve PFS in STR patients. Furthermore, GTR, tumor development in the unilateral ventricle, and MIB-1LI < 5% were found to be favorable factors affecting the prognosis of CNs.