Aggressive Pathological Features Research Articles

PD10-04 SUVMAX OF THE PRIMARY PROSTATE LESION ON THE PSMA PET CT: AN INDICATOR OF AGGRESSIVE PATHOLOGY

You have accessJournal of UrologyCME1 Apr 2023PD10-04 SUVMAX OF THE PRIMARY PROSTATE LESION ON THE PSMA PET CT: AN INDICATOR OF AGGRESSIVE PATHOLOGY Amandeep Arora, Archi Agarwal, Mahendra Pal, Ganesh Bakshi, Venkatesh Rangarajan, Gujela Ajit, Santosh Menon, and Gagan Prakash Amandeep AroraAmandeep Arora More articles by this author , Archi AgarwalArchi Agarwal More articles by this author , Mahendra PalMahendra Pal More articles by this author , Ganesh BakshiGanesh Bakshi More articles by this author , Venkatesh RangarajanVenkatesh Rangarajan More articles by this author , Gujela AjitGujela Ajit More articles by this author , Santosh MenonSantosh Menon More articles by this author , and Gagan PrakashGagan Prakash More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003250.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PSMA PET CT scans are being increasingly utilized in the staging evaluation of prostate cancer. However, there is limited data regarding the utility of the standardized uptake value (SUVmax) of the primary prostate lesion in the PSMA PET scan. Here, we evaluated whether the SUVmax of the primary prostate lesion can indicate aggressive pathological features in patients undergoing radical prostatectomy (RP) with an extended pelvic nodal dissection (PLND). METHODS: We retrospectively reviewed a prospectively maintained institutional database for prostate cancer patients from 2015-2022 who had a PSMA PET scan for their staging evaluation followed by a RP with PLND. Data was collected for clinico-pathological variables. The SUVmax of the primary lesion in the prostate was noted & compared across the pathological Gleason grade groups (GGG). We also checked whether the SUVmax had an association with Gleason upgrading & pathological nodal status. RESULTS: A total of 205 patients were included & were stratified into the following clinical risk groups based on MRI & PSMA-PET scans: 6 (2.9%) low-risk, 49 (23.9%) intermediate-risk, 46 (22.4%) high-risk localized, 89 (43.4%) locally-advanced node-negative & 15 (7.3%) node-positive patients. The median SUVmax of the primary prostate lesion for pathological GGG 1, 2, 3, 4 & 5 were 6.45, 11.3, 18.11, 25.51 & 24.37 respectively (p<0.001). For the 153 patients with a Gleason score 6-7 on transrectal biopsy, 19 patients had an upgrading of their score to >8 on the final pathology. The median SUV max of the prostate lesion in these 19 patients was significantly higher [median 22.37 (IQR 15.5–33.1)] than that in the remaining 134 patients with biopsy Gleason score 6-7 who did not have an upgrading to >8 on the final pathology [median 11.3 (IQR 7.4–17.5)]; p<0.001 (Figure 1). Also, the median SUVmax of the primary prostate lesion in patients who were true negatives for nodes, as per the PSMA-PET scan & final pathology, was significantly lower (12.8 vs 26.4, p<0.001) than that in patients who were false negative (cN0 on PSMA but pN+ in final pathology). CONCLUSIONS: Higher SUVmax of the primary prostate lesion is an indicator of aggressive pathological behaviour in the form of Gleason upgrading positive pelvic nodal status. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e327 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amandeep Arora More articles by this author Archi Agarwal More articles by this author Mahendra Pal More articles by this author Ganesh Bakshi More articles by this author Venkatesh Rangarajan More articles by this author Gujela Ajit More articles by this author Santosh Menon More articles by this author Gagan Prakash More articles by this author Expand All Advertisement PDF downloadLoading ...

MET Exon 14 Variants in Non-Small Cell Lung Carcinoma: Prevalence, Clinicopathologic and Molecular Features

Somatic MET exon 14 skipping mutations (MET ex14) are targetable driver mutations for non-small cell lung cancer (NSCLC), responsive to MET inhibitors. Objective: This study seeks to further characterize the clinicopathologic features and mutational profile of MET ex14 variant NSCLC. Design: Retrospective review of all MET ex14 tested NSCLC. Testing for selected BRAF, EGFR, HER2, KRAS, and MET mutations was performed using a clinically validated NGS assay, followed by MiSeq sequencing. Variants were classified as significant (Tier1/2) or variants of uncertain significance (VUS) per 2017 AMP/ASCO/CAP Joint Consensus Guidelines. PD-L1 expression was assessed by immunohistochemistry. Results: Of 2296 NSCLCs tested between 2017-7/2019, MET ex14 variants were present in 44 (1.9%). A total of 32 of 44 variants were MET exon 14 skipping, while the other 12 mutations were significant missense (3) or VUS (9). Of nine VUS, five were adjacent to the canonical splice site and likely to impact splicing. Four cases had concomitant mutations. Of 35 cases with known clinical staging, stage 1–2 = 20 (57%), stage 3 = 3 (9%), and stage 4 = 12 (34%). Of 19 resected NSCLSs, histological types and growth pattern included 7 lepidic pattern-predominant. A high percentage of tumors with MET ex14 mutations are positive for PD-L1, and the percentage of cases with PD-L1 expression &gt;50% trends higher in more advanced disease. Conclusions: Most MET variants identified in our cohort (73%) are MET ex14 skipping. The prevalence of MET ex14 variants is 1.9%, and a large percentage of tumors has lower clinical stage and less aggressive pathologic features.

MUC1 Expressions and Its Prognostic Values in US Gastric Cancer Patients.

This study aims to evaluate the prognostic value of MUC expression in US GC patients. A total of 70 tumor specimens were collected from GC patients who underwent surgery or endoscopic resection between 2013 and 2019 at a tertiary referral center in the US. MUC expression status including MUC1, MUC2, MUC5AC, and MUC6 was evaluated by immunohistochemical staining. The positive rates of MUC1, MUC2, MUC5AC, and MUC6 were 71.4%, 78.6%, 74.3%, and 33.3%, respectively. Patients with positive MUC1 expression had a significantly higher rate of aggressive pathologic features including diffuse-type cancer (42.0% vs. 0%; p < 0.001), advanced GC (80.0% vs. 30.0%, p < 0.001), lymph node metastasis (62.0% vs. 20.0%; p = 0.001), and distant metastasis (32.0% vs. 5.0%; p = 0.017) compared with those with negative MUC1 expression. However, the differences in the pathologic features were not observed according to MUC2, MUC5AC, and MUC6 expression status. In early gastric cancer (EGC), patients with a high level of MUC1 expression showed a higher rate of lymphovascular invasion (71.4% vs. 21.4%; p = 0.026) and EGC meeting non-curative resection (85.7% vs. 42.9%; p = 0.061) than those with negative MUC1. In US GC patients, MUC1 expression is associated with aggressive pathological features, and might be a useful prognostic marker.

Prognostic value of preoperative [68Ga]Ga-FAPI-04 PET/CT in patients with resectable pancreatic ductal adenocarcinoma in correlation with immunohistological characteristics.

Our aim was to assess the prognostic value of [68Ga]Ga-FAPI-04 positron emission tomography (PET) uptake in PDAC and to evaluate the correlation between in vivo lesional radioactivity with pathological characteristics of pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed treatment-naïve PDAC patients who underwent preoperative [68Ga]Ga-FAPI-04 PET/CT followed by pancreatectomy. The tracer uptake was determined as maximum tumor standardized uptake value (SUVmax), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) as well total pancreatic uptake (TSUVmax), total FAPI-avid pancreatic volume (FPV), and total pancreatic FAP expression (TPF). Spearman's correlation analysis was performed to evaluate the association between [68Ga]Ga-FAPI-04 PET/CT imaging and ex vivo immunohistological FAP expression and pathological characteristics of surgical specimens (differentiation, size, vascularity, perineural invasion, and lymph node metastases). Kaplan-Meier and hazard ratio (HR, log-rank) methods were used to evaluate the prognostic value of [68Ga]Ga-FAPI-04 PET/CT and clinicopathological factors. Thirty-seven surgical PDAC patients were included. The ex vivo expression of FAP was significantly associated with the tumor SUVmax and TLF. FAP expression was more abundant in poorly differentiated PDAC than in well- to moderately differentiated neoplasms. Tumor SUVmax or TLF and pancreatic TSUVmax or TPF were significantly correlated with tumor size, differentiation, and perineural invasion, respectively. SUVmax had a significant independent prognostic value for recurrence-free survival (HR = 2.46, P < 0.05), while [68Ga]Ga-FAPI-04 TPF predicted overall survival (HR = 12.82, P < 0.05). The in vivo [68Ga]Ga-FAPI-04 uptake in localized PDAC showed a significant correlation with ex vivo FAP expression and aggressive pathological characteristics. [68Ga]Ga-FAPI-04 PET/CT also presented a potential for postoperative prognostication of PDAC. Elevated fibroblast activity induced by obstructive pancreatitis might be associated with the patient's survival.

WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.

The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.

Prediction for Aggressiveness and Postoperative Recurrence of Hepatocellular Carcinoma Using Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

To investigate the predictive value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) features on the pathologic grade, microvascular invasion (MVI), and cytokeratin-19 (CK19) expression in hepatocellular carcinomas (HCC), and to evaluate their association with postoperative recurrence of HCC. This retrospective study included 147 patients with surgically confirmed HCCs who underwent gadoxetic-enhanced MRI. The lesions were evaluated quantitatively in terms of the relative enhancement ratio (RER), and qualitatively based on imaging features and clinical parameters. Logistic regression analyses were performed to investigate the value of these parameters in predicting the pathologic grade, MVI, and CK19 in HCC. Predictive factors for postoperative recurrence were determined using a Cox proportional hazards model. Peritumoral enhancement (odds ratio [OR], 3.396; p=0.025) was an independent predictor of high pathologic grades. Serum protein induced by vitamin K absence or antagonist (PIVKA) level > 40 mAU/mL (OR, 3.763; p=0.018) and peritumoral hypointensity (OR, 4.343; p=0.003) were independent predictors of MVI. Predictors of CK19 included serum alpha-fetoprotein (AFP) level > 400 ng/mL (OR, 4.576; p=0.005), rim enhancement (OR, 5.493; p=0.024), and lower RER (OR, 0.013; p=0.011). Peritumoral hypointensity (hazard ratio [HR], 1.957; p=0.027) and poor pathologic grades (HR, 2.339; p=0.043) were independent predictors of recurrence. We demonstrated the value of preoperative gadoxetic-enhanced MRI in predicting aggressive pathological features of HCC. Poor pathologic grades and peritumoral hypointensity may independently predict the recurrence of HCC.

Oncologic safety of colonic stenting as a bridge to surgery in left-sided malignant colonic obstruction: Current evidence and prospects

Approximately 7%-29% of patients with colorectal cancer present with colonic obstruction. The concept of self-expandable metal stent (SEMS) insertion as a bridge to surgery (BTS) is appealing. However, concerns on colonic stenting possibly impairing oncologic outcomes have been raised. This study aimed to review current evidence on the short- and long-term oncologic outcomes of SEMS insertion as BTS for left-sided malignant colonic obstruction. For short-term outcomes, colonic stenting facilitates a laparoscopic approach, increases the likelihood of primary anastomosis without a stoma, and may decrease postoperative morbidity. However, SEMS-related perforation also increases local recurrence and impairs overall survival. Moreover, colonic stenting may cause negative oncologic outcomes even without perforation. SEMS can induce shear forces on the tumor, leading to increased circulating cancer cells and aggressive pathological characteristics, including perineural and lymphovascular invasion. The conflicting evidence has led to discordant guidelines. Well-designed collaborative studies that integrate both oncologic outcomes and data on basic research (e.g., alteration of circulating tumors) are needed to clarify the actual benefit of colonic stenting as BTS.

Is palpable DCIS more aggressive than screen-detected DCIS?

BackgroundPalpable ductal carcinoma in-situ (pDCIS) is a subset of DCIS presenting with a clinical mass. We hypothesized pDCIS would have more aggressive clinical and pathological features, and higher rates of recurrence and upgrade to invasive disease compared to screen-detected DCIS. Materials and methodsWe performed a retrospective analysis of female patients (age 28–76) with DCIS on core-needle biopsy. pDCIS patients had a physician documented palpable mass prior to initial biopsy. Descriptive statistics were performed to compare groups. ResultsThis study included 83 patients, 26 had pDCIS and 57 had screen-detected DCIS. Mean duration of follow-up was 49.4 months. pDCIS patients had significantly larger lesions (p = 0.03) which were more frequently biopsied via ultrasound (p = 0.002). In multivariate analysis, pDCIS was associated with ultrasound guided core needle biopsy, size of DCIS >2 cm, and comedo pattern (p = 0.001, p = 0.007 and p = 0.022, respectively). 7.7 % of pDCIS cases versus 3.5 % of screen-detected cases were upgraded to invasive cancer (p = 0.59). There was no difference in local recurrence (p = 0.55) between groups. Neither group experienced regional or distant recurrence. ConclusionspDCIS was associated with some aggressive pathologic and clinical features and was more frequently diagnosed by ultrasound guided core-needle biopsy than screen-detected DCIS. However, there was no significant difference in rate of recurrence or upgrade to invasive disease between groups. Key messageAlthough pDCIS was associated with some aggressive pathologic and clinical features, there was no significant difference in rate of recurrence or upgrade to invasive disease compared to screen-detected DCIS.

Clinicopathological characteristics, treatments, and prognosis of breast ductal carcinoma in situ with microinvasion: A narrative review.

Ductal carcinoma in situ with microinvasion (DCIS-MI) is defined as ductal carcinoma in situ (DCIS) with a microscopic invasive focus ≤1 mm in the longest diameter. The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI. This narrative review described recently reported literature regarding the characteristics, treatment, and prognosis of it. Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word: breast cancer, microinvasion, DCIS, DCIS-MI, and invasive ductal carcinoma (IDC). DCIS-MI tends to express more aggressive pathological features such as necrosis, HER2+, ER- or PR-, and high nuclear grade. The overall prognosis of DCIS-MI is typically good, however, some indicators such as young age, HR-, HER2+ and multimicroinvasive lesions, were associated with worse prognoses. And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC. Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR- orHER2+ to improve the prognosis. DCIS-MI has more aggressive pathological features, which may suggest its biological behavior is worse than that of DCIS and similar to early IDC. Although the overall prognosis of DCIS-MI is good, when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status, HER2 expression and axillary lymph node status of patients, because these may affect the prognosis and treatment response.

Malignant germ cell tumors in men aged 50 years and over are associated with adverse pathologic features and higher stage at presentation

BackgroundGerm cell tumors (GCT) are the most common malignancy in men in the third and fourth decades of life. The occurrence of malignant GCT in men aged 50 years or over is rare, and their histopathologic characteristics and outcome is insufficiently characterized in the medical literature. Hence, we report the histopathologic features and clinical outcome of malignant GCTs in men aged ≥50 years at our institution. DesignWe performed a retrospective search of our database from 2005 to 2021 to identify men aged 50 years or older with malignant GCT. Cases of spermatocytic tumor were excluded. Clinical and histopathologic features of the tumors were reviewed. ResultsForty-seven cases were identified, showing a sharp decline in incidence over the age of 65. Thirty-nine (83 %) tumors were testicular while eight (17 %) were non-testicular in presentation. Cases included 26 (55 %) seminomas, 15 (32 %) non-seminoma/mixed malignant GCT, and 5 (11 %) regressed testicular germ cell tumors. The most common component in mixed malignant GCTs was embryonal carcinoma (77 %), followed by seminoma and yolk sac tumor (62 % each). Germ cell neoplasia in situ (GCNIS) accompanied 57 % of the cases. Aggressive pathologic features, including lymphovascular invasion, retroperitoneal/lymph node involvement and higher stage at presentation, were identified in a significant proportion of cases (36/47, 77 %). Clinical follow up showed six patients (14 %) died of disease-related causes. ConclusionOur findings expand and corroborate the previously reported data on malignant GCT in older men. Unique characteristics include tendency for higher stage at presentation with adverse pathologic features and more aggressive clinical course.

Tumor-associated tissue eosinophilia promotes angiogenesis and metastasis in head and neck squamous cell carcinoma

Eosinophils are terminally differentiated leukocytes that participate in the process of chronic inflammation and allergy and are able to release multiple cytokines into the surrounding tissue environment. Tumor-associated tissue eosinophilia (TATE) is the presence of eosinophils in the tumor or in the neighboring stroma and has been observed in various types of cancer. In head and neck squamous cell carcinoma (HNSCC), the clinical relevance of TATE has not been concluded yet because of the inconsistent results in different studies. In our study, we focus on the prognostic effects of TATE on HNSCC and how TATE can influence tumor behavior and tumor microenvironment. We first showed that in both the TCGA-HNSC cohort and our cohort of patients with HNSCC who had received curative surgery, TATE is correlated with worse overall survival. To investigate the underlying mechanism of how TATE leads to poor clinical outcomes, we showed that activated eosinophils produce a variety of cytokines and chemokines, and activated TATE-derived culture medium promotes tumor migration mainly through CCL2. We also showed that eosinophils are capable of inducing angiogenesis and that HNSCC samples enriched with TATE are highly correlated with tumor angiogenesis. Furthermore, HNSCC enriched with TATE had more aggressive pathological features, including regional lymph node metastasis, perineural invasion, lymphovascular invasion, and tumor growth. Lastly, we showed that HNSCC enriched with TATE is associated with immunosuppressive tumor microenvironment. Taken together, our results suggest that TATE promotes cancer metastasis and angiogenesis which results in a poor clinical outcomes in HNSCC.

Pathologic Implications of Magnetic Resonance Imaging-detected Extramural Venous Invasion of Rectal Cancer

BackgroundExtramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer. Materials and MethodsThis study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT. ResultsOf the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT. ConclusionMR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT.

Association between decreased ipsilateral renal function and aggressive behavior in renal cell carcinoma

BackgroundTo assess prognostic value of pre-operative ipsilateral split renal function (SRF) on disease-free survival (DFS) and its association with aggressive pathological features in renal cell carcinoma (RCC) patients. MethodsWe examined patients registered in SNUG-RCC-Nx who underwent partial or radical nephrectomy at Seoul National University Hospital between January 1, 2010 and December 31, 2020. Patients with the following criteria were excluded from the study. 1) non-kidney origin cancer or benign renal tumor, 2) no pre-operative Tc 99 m-DTPA renal scan, 3) single kidney status or previous partial or radical nephrectomy, and 4) bilateral renal mass. Finally, 1,078 patients were included.ResultsAmong 1,078 patients, 899 (83.4%) showed maintained ipsilateral SRF on DTPA renal scan; 179 patients (16.6%) showed decreased SRF. The decreased SRF group showed significantly large tumor size (maintained vs. decreased SRF; 3.31 ± 2.15 vs. 6.85 ± 3.25, p < 0.001), high Fuhrman grade (grade 3–4) (41.7% vs. 55.6%, p < 0.001), and high T stage (T stage 3–4) (9.0% vs. 20.1%, p < 0.001). Pathological invasive features, including invasion of the renal capsule, perirenal fat, renal sinus fat, vein, and collecting duct system, were associated with low SRF of the ipsilateral kidney. Univariate Cox regression analysis identified higher SSIGN (The stage, size, grade, and necrosis) score and decreased ipsilateral SRF as significant risk factors, while multivariate analysis showed SSIGN (5–7) (hazard ratio [HR] 11.9, p < 0.001) and SSIGN (8–10) (HR 69.2, p < 0.001) were significantly associated with shortened DFS, while decreased ipsilateral SRF (HR 1.75, p = 0.065) showed borderline significance. Kaplan–Meier analysis showed that decreased ipsilateral SRF (< 45%) group had shorter DFS than the other group (median DFS: 90.3 months vs. not reached, p < 0.001).ConclusionsAmong unilateral RCC patients, those with low ipsilateral SRF showed poor prognosis with pathologically invasive features. Our novel approach may facilitate risk stratification in RCC patients, helping formulate a treatment strategy.

Diagnóstico incidental del cáncer de vejiga en España. Estudio observacional a nivel nacional

IntroductionBladder cancer (BC) is a common malignancy in Spain. The aims of this study were: to identify the proportion of patients diagnosed with BC incidentally or after symptomatic presentation in a contemporary period in Spain; to compare demographic, clinical, and pathologic characteristics between these groups. MethodsThis was a retrospective analysis of a multi-centre observational study of 26 hospitals in the Spanish National Health System of all BCs newly diagnosed in 2011. The study represented 21.5% of the Spanish population and hospitals were selected in proportion to Spain's regions to ensure a representative sample. Patients were categorized by whether the cancer was diagnosed incidentally or after symptomatic presentation and baseline demographic, pathologic, and clinical characteristics were analyzed. Results2472 were newly diagnosed with BC at the 26 participating Spanish hospitals with 308 (12.5%) of cases diagnosed incidentally and 2164 (87.5%) diagnosed after symptomatic presentation. No differences were observed between patients diagnosed incidentally vs. symptomatically in terms of demographics or measured co-morbidities. Compared to symptomatically diagnosed bladder tumours, those diagnosed incidentally were more likely to have a papillary appearance, to be significantly smaller, and less likely to have positive/suspicious cytology. Additionally, incidentally diagnosed bladder tumours were less likely to be muscle-invasive (11.7% vs. 25.0%, P < .01) nor aggressive at pathology, with 33.6% Grade 3 compared to 50.1%, (P < .01). ConclusionsWe identified a significant percentage (12.5%) of new bladder cancer diagnosis made incidentally in a representative sample of the Spanish population. These tumours exhibited less aggressive pathologic characteristics than their symptomatic counterparts.

Early-Onset Gastric Cancer from a Geographic Area of High Gastric Cancer Incidence in North-East India: a Retrospective Study.

We aim to report about the clinico-pathological characteristics of early-age gastric cancer in North-East India. It is a retrospective and observational study conducted in a tertiary care cancer centre in North-East India. We reviewed physical case records and the hospital electronic medical record system. The study population included all patients of age 40years or less, with a confirmed diagnosis of gastric adenocarcinoma, who received treatment in the institute. The duration of the study was from 2016 to 2020. Data was collected using a pre-designed proforma, and the results were presented as percentages, ratios, median values and range. A total of 79 patients with early-age gastric cancer were found during the study period. There was female preponderance (45:34). Out of the total, 43% presented in stage IV. Most of them had good performance status (87.3% had ECOG 0-2), and none of them had documented co-morbid illness. Poorly differentiated adenocarcinoma and signet ring cell carcinoma were seen in 36.7% and 25.3% patients, respectively. Only 25 patients (31.6%) underwent definitive surgery, and they had a high nodal burden with a median metastatic lymph nodal ratio of 0.35 (range 0 to 0.91). Out of them, 40% developed systemic recurrence within a short span of time (median time to recurrence being 9.5months). Peritoneal recurrence was the most common site of failure (80%). Early-age gastric cancer has been associated with aggressive pathological features and poor clinical outcomes in North-East India.

Incidental diagnosis of bladder cancer in a national observational study in spain

IntroductionBladder cancer (BC) is a common malignancy in Spain. The aims of this study were: to identify the proportion of patients diagnosed with BC incidentally or after symptomatic presentation in a contemporary period in Spain; to compare demographic, clinical, and pathologic characteristics between these groups. MethodsThis was a retrospective analysis of a multi-centre observational study of 26 hospitals in the Spanish National Health System of all BCs newly diagnosed in 2011. The study represented 21.5% of the Spanish population and hospitals were selected in proportion to Spain’s regions to ensure a representative sample. Patients were categorized by whether the cancer was diagnosed incidentally or after symptomatic presentation and baseline demographic, pathologic, and clinical characteristics were analyzed. Results2472 were newly diagnosed with BC at the 26 participating Spanish hospitals with 308 (12.5%) of cases diagnosed incidentally and 2164 (87.5%) diagnosed after symptomatic presentation. No differences were observed between patients diagnosed incidentally vs. symptomatically in terms of demographics or measured co-morbidities. Compared to symptomatically diagnosed bladder tumours, those diagnosed incidentally were more likely to have a papillary appearance, to be significantly smaller, and less likely to have positive/suspicious cytology. Additionally, incidentally diagnosed bladder tumours were less likely to be muscle-invasive (11.7% vs. 25.0%, p < 0.01) nor aggressive at pathology, with 33.6% Grade 3 compared to 50.1%, (p < 0.01). ConclusionsWe identified a significant percentage (12.5%) of new bladder cancer diagnosis made incidentally in a representative sample of the Spanish population. These tumours exhibited less aggressive pathologic characteristics than their symptomatic counterparts.

Clinical features and prognostic factors of breast cancer in young women: a retrospective single-center study.

This research aims to characterize the differences in clinical features and prognostic factors between younger and older breast cancer (BC) patients in China. All patients who were recently diagnosed with BC between January 1, 2015 and December 31, 2016 at Shanxi Province Cancer Hospital were recruited. We collected the epidemiological and clinical data as well as the follow-up information. Out of the 1968 BC patients who met the criteria for analysis, 227 (11.53%) were under 40years of age with a median age of 34years at diagnosis. All patients were classified into the age < 40, age 40-59, and age ≥ 60 groups. There were significant differences in the histology, tumor size, T stage, grade, and human epidermal growth factor receptor-2 (HER-2) levels among the three groups (all P < 0.05). The 5-year overall survival (OS) rates were 86.34%, 89.58%, and 84.84% for the age < 40, age 40-59, and age ≥ 60 groups, respectively. The TNM stage was the only predictor of clinical outcome in all BC patients. The prognostic value of intrinsic subtypes for OS was different among the three groups. Our study helped identify an age-related prognostic indicator of adverse events in BC patients and showed that young women with BC exhibited more aggressive clinical and pathological features. Our findings may facilitate clinical management and therapeutic interventions in young BC patients, especially in young women with a history of exposure to risk factors and age < 40years.

High MT2A Expression Predicts Worse Prognosis in Patients with Urothelial Carcinoma

Introduction: Dysregulation of metal ion homeostasis is associated with urothelial carcinogenesis. From a published urinary bladder urothelial carcinoma (UBUC) transcriptome, we identified metallothionein 2A (MT2A) as the most significantly upregulated gene implicated in cancer progression among metal ion binding-related genes. Therefore, we analyzed the association between MT2A expression and clinical significance in our well-characterized cohort of patients with upper tract urothelial carcinoma (UTUC) and UBUC. Methods: We retrospectively reviewed the clinicopathological characteristics of 295 and 340 patients with UBUC and UTUC, respectively. MT2A expression was assessed using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson’s χ² test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. Results: High MT2A expression was significantly associated with aggressive pathological features including high tumor stage, lymph node metastasis, high tumor grade, vascular invasion, and perineural invasion. In the Kaplan-Meier analysis, high MT2A expression was significantly correlated with poor DSS (p < 0.0001) and MFS (p < 0.0001); in the multivariate analysis, it was an independent predictor of CSS (p < 0.001) and MFS (p = 0.001). Gene coexpression analysis demonstrated that MT2A overexpression promotes UC progression through complement activation. Conclusion: High MT2A expression correlated with aggressive UC features and was an independent predictor of cancer metastasis and patient survival, suggesting its role in risk stratification and decision-making in patients with UTUC and UBUC.

Preoperative gadoxetic acid-enhanced MRI predicts aggressive pathological features in LI-RADS category 5 hepatocellular carcinoma

To investigate whether Liver Imaging Reporting and Data System (LI-RADS) imaging features and non-LI-RADS imaging features can predict aggressive pathological features in adult patients with hepatocellular carcinoma (HCC). From February 2018 to September 2021, 236 adult patients with cirrhosis or hepatitis B virus infection in which liver cancer was suspected underwent MRI within 1 month before surgery. Significant MRI findings and alpha-fetoprotein (AFP) level predicted high-grade HCC and microvascular invasion (MVI) by univariate and multivariate logistic regression models. The study included 112 patients with histopathologically confirmed liver cancer (≤5 cm), 35 of whom (31.3%) high-grade HCC and 42 of 112 (37.5%) patients had MVI. Mosaic architecture (odds ratio [OR]=6.031; 95% confidence interval [CI]: 1.366, 26.626; p=0.018), coronal enhancement (OR=5.878; 95% CI: 1.471, 23.489; p=0.012), and intratumoural vessels (OR=5.278; 95% CI: 1.325, 21.020; p=0.018) were significant independent predictors of high-grade HCC. A non-smooth tumour margin (OR=10.237; 95% CI: 1.547, 67.760; p=0.016), coronal enhancement (OR=3.800; 95% CI: 1.152, 12.531; p=0.028), and peritumoural hypointensity on the hepatobiliary phase (HBP; OR=10.322; 95% CI: 2.733, 38.986; p=0.001) were significant independent predictors of MVI. In high-risk adult patients with single LR-5 HCC (≤5 cm), mosaic architecture, coronal enhancement, and intratumoural vessels are independent predictors of high-grade HCC. Non-smooth tumour margin, coronal enhancement, and peritumoural hypointensity on HBP independently predicted MVI.

Abstract 2270: Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking

Abstract Introduction: Hyperlipidemia has been associated with increased risk of advanced stage and high Gleason grade prostate cancer (PCa), yet the underlying mechanism is not completely understood. Quaking (QKI) is an RNA-binding protein (RBP) that regulate lipid metabolism. For PCa, QKI overexpression has been associated with increased chance of metastatic recurrence. Method: We performed RNA sequencing of prostate cancer tissues of hyperlipidemia (n = 12) and normolipidemia (n=32). Tissue samples were acquired by MRI-US fusion targeted biopsy. DESeq2 and GSEA was used to identify differently expressed genes and enriched genesets. A web-based RBP motif screening tool TRANSITE was utilized to identify active RBPs in hyperlipidemia-associated PCa. Results: PCa samples of hyperlipidemia patients exhibited poorer histology than normolipidemia PCA. RNA sequencing found that hyperlipidemia-associated PCa is enriched of Myc-regulated genes as well as interferon or innate immunity-associated genes. Interestingly, hyperlipidemia-associated PCa gene expression signature identified PCa samples devoid of common PCa genetic alterations - TMPRSS2-ERG fusion and PTEN deletion/mutation. RBP motif screening found QKI as one of the top enriched RBP in hyperlipidemia-associated PCa transcriptome. In a separate a consecutive radical prostatectomy series (n=190), we found that QKI-high (immunohistochemistry staining score 2-3) tumors had significantly higher serum cholesterol than QKI-low (score 0-1) tumors. Overexpression and knockdown experiments proved that QKI is responsible of rapid cell proliferation and interferon-related inflammatory gene expressions, In silico analysis predicted QKI overexpressing cancer cells are susceptive to stain-mediated ferroptosis-like cell death. Mechanistically, QKI regulates expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), which dictates the sensitivity of QKI overexpressing cells to ferroptosis. Conclusion: Hyperlipidemia was associated with aggressive pathologic characteristics of PCa without TMPRSS2-ERG fusion or PTEN deletion/mutation, and high tissue expression of QKI, an RNA-binding protein. QKI overexpression in PCa increased sensitivity to ACSL4-mediated ferroptosis by statins. This explains the epidemiological associations between hyperlipidemia and PCa, and will guide molecular subtype-driven drug repurposing studies. Citation Format: Hyun Ho Han, Jin Sol Sung, Dong Wook Song, Cheol Keun Park, Nam Hoon Cho, Young Deuk Choi, Woo Jin Ko. Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2270.