Frequent gene mutations and the correlations with clinicopathological features in clear cell renal cell carcinoma: preliminary study based on Chinese population and TCGA database.

BACKGROUND: Large-scale sequencing plays important roles in revealing the genomic map of ccRCC and predicting prognosis and therapeutic response to targeted drugs. However, the relevant clinical data is still sparse in Chinese population. METHODS: Fresh tumor specimens were collected from 66 Chinese ccRCC patients, then the genomic RNAs were subjected to whole transcriptome sequencing (WTS). We comprehensively analyzed the frequently mutated genes from our hospital's cohort as well as TCGA-KIRC cohort. RESULTS: VHL gene is the most frequently mutated gene in ccRCC. In our cohort, BAP1 and PTEN are significantly associated with a higher tumor grade and DNM2 is significantly associated with a lower tumor grade. The mutant type (MT) groups of BAP1 or PTEN, BAP1 or SETD2, BAP1 or TP53, BAP1 or MTOR, BAP1 or FAT1 and BAP1 or AR had a significantly correlation with higher tumor grade in our cohort. Moreover, we identified HMCN1 was a hub mutant gene which was closely related to worse prognosis and may enhance anti-tumor immune responses. CONCLUSIONS: In this preliminary research, we comprehensively analyzed the frequently mutated genes in the Chinese population and TCGA database, which may bring new insights to the diagnosis and medical treatment of ccRCC.

Tumor grade and progesterone receptor status in predicting benefit of chemotherapy in high genomic risk breast cancer.

BACKGROUND: Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy. RESEARCH DESIGN AND METHODS: Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database. RESULT: We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p ≥ 0.05). CONCLUSION: Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making.

The Interplay Between Adult-Onset Hypogonadism and Prostate Cancer: A Literature Review.

The interplay between endogenous testosterone (Te) and prostate cancer (PCa) has long been recognized, with androgen deprivation therapy (ADT) being a cornerstone of advanced and metastatic PCa management. However, the association between Te levels and PCa risk remains complex and not fully understood. This review delves into the complex relationship between adult-onset hypogonadism (AOH) and PCa, shedding light on the complexities surrounding PCa risk and disease aggressiveness. Despite the significant prevalence of PCa among men, particularly as they age, and the emergence of AOH as a prevalent health concern, data regarding their association remains heterogeneous and inconsistently documented. While some studies suggest a potential correlation between low Te levels and decreased PCa detection rates, others indicate a higher risk of aggressive pathological features, primarily observed in prostatectomy cohorts. It's noteworthy that there's evidence indicating hypogonadal men might face an increased risk of reclassification during active surveillance (AS) of low-risk disease. This is supported by the observation of elevated rates of disease upgrading in historical cohorts of low-risk prostatectomies. These contradictory findings are poorly reflected in treatment guidelines. Further research is imperative to comprehensively understand the clinical and associative correlations between AOH and PCa risk and biology, thereby informing more effective management strategies in the future.

Effectiveness of Apparent Diffusion Coefficient Values in Predicting Pathologic Subtypes and Grade in Non-Small-Cell Lung Cancer.

BACKGROUND AND OBJECTIVE: The aim of this study is to evaluate the effectiveness of apparent diffusion coefficient (ADC) values in predicting pathologic subtypes and grade in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: From January 2018 to March 2020, 48 surgically diagnosed NSCLC cases were included in this study. To obtain ADC values, ADC maps were constructed, and a region of interest was put on the tumor. The values were measured three times from different places of the lesion, and the mean value of these measurements was recorded. All MRI scans were evaluated by two radiologists in consensus. RESULTS: A total of 14 cases were squamous cell cancer, 32 cases were adenocarcinoma, and 2 cases were large cell carcinoma. The mean ADC values of adenocarcinoma, squamous cell carcinoma, and large cell cancer were 1.51 ± 0.19 × 10-3 mm2/s, 1.32 ± 0.15 × 10-3 mm2/s, and 1.39 ± 0.25 × 10-3 mm2/s, respectively. There were 11 grade 1, 27 grade 2, and 10 grade 3 NSCLC cases. The mean ADC value was 1.44 ± 0.14 × 10-3 mm2/s in grade 1 tumors, 1.25 ± 0.10 × 10-3 mm2/s in grade 2 tumors, and 1.07 ± 0.15 × 10-3 mm2/s in grade 3 tumors. The cut-off value to discriminate grade 2 from grade 1 tumors was 1.31 ± 0.11 × 10-3 mm2/s (85% sensitivity, 75% specificity). The cut-off value to discriminate grade 3 from grade 2 tumors was 1.11 ± 0.15 × 10-3 mm2/s (87% sensitivity, 69% specificity). CONCLUSIONS: ADC values can accurately predict NSCLC histopathologic subtypes and tumor grade.

Quantitative CT Morphometrics: A Novel Approach for Predicting the Bladder Cancer Grade.

Background and objective Bladder cancer (BC) is a common urothelial neoplasm, with non-muscle invasive forms comprising about 75% of cases and generally having better outcomes than muscle-invasive types. Accurate preoperative grading and staging of BC are essential for appropriate treatment planning. This study investigates the efficacy of computerized tomography (CT) in correlating the morphological features of tumors to predict the histopathological grades of BC.  Materials and methods This retrospective cohort involved 100 patients diagnosed with non-muscle invasive BC, who underwent transurethral resection of bladder tumor (TUR-BT) between January 2010 and August 2021. CT imaging, utilizing a 128-slice CT scanner, was employed to measure the tumor height (H) and contact length (CL). The study considered morphometric parameters across axial, coronal, and sagittal planes. Statistical analyses were conducted, comparing radiological findings with histopathological evaluations. Tumor grading was determined according to the 2004/2016 WHO classification. Results Among the 100 patients with primary bladder tumors, 15 were female and 85 were male, with a mean age of 65.28 ± 7.11 years. Furthermore, 58 had high-grade bladder tumors, while 42 had low-grade bladder tumors. Across all planes, high-grade tumors exhibited higher values for the tumor H, CL, and the tumor height-to-contact length (H/CL) ratio compared to low-grade tumors (p<0.05). Notably, the specificity, sensitivity, and diagnostic accuracy of the tumor CL were higher than those of the tumor H and the tumor H/CL ratio. A tumor CL exceeding 19.1mm measured in the axial plane demonstrated 83% sensitivity and specificity for high-grade tumors. Conclusion The measured CL of the tumor in the axial plane on computerized tomography urography has high sensitivity and specificity in detecting high-grade tumors.

A Concordance Between Clinical and Pathological Tumor Staging of Oral Squamous Cell Carcinoma: An Institutional Study.

BACKGROUND: Among oral diseases, oral cancer is the primary cause of death and poses a serious health risk. Primary tumor (T) - regional lymph node (N) - distant metastasis (M) comprising (TNM) staging is crucial for planning treatment strategies for patients with oral squamous cell carcinoma (OSCC). AIM: This study evaluated the predictive accuracy of clinical TNM staging of OSCC to histopathological staging (pTNM) in an institutional setting. MATERIALS AND METHODS: Fifty-four consecutive histologically confirmed, surgically treated OSCC cases were evaluated for TNM staging. The study compared the clinical staging at the time of surgery with the pathological staging obtained from excisional biopsy reports. Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) was used for the data compilation and descriptive analysis. The chi-square test, analysis of variance (ANOVA), and Tukey's Honest Significant Difference (HSD) posthoc test were used to compare the data for statistical significance with p value <0.05 using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY). RESULTS: The alveolar mucosa (n=22, 40.74%) was the most frequently occurring site, followed by the tongue (n=17, 31.48%). Out of the 54 included cases, based on clinical tumor size, there were T1 (n=6), T2 (n=13), T3 (n=13), T4a (n=16) and T4b (n=6). T2 tumors were usually upstaged (n=7) while T4a (n=8) tumors were most often downstaged. T4a (n=8) had the best concordance between clinical and histopathological staging, followed by T2, T3, and T1. In nodal status, N1 showed the most variation. The chi-squared test showed statistical significance for tumor size comparison (p <0.001) and nodal status comparison (p=0.002). ANOVA test did not show any statistical significance. Tukey's HSD posthoc test showed statistical significance (p=0.034) for N0 and N1 status. The highest concordance was shown by N0 and N1 followed by N2b. CONCLUSION: Preoperative radiological and clinical assessments are essential for deciding on a patient's course of treatment. However, not all patients may require radiographs to determine tumor size or nodal status assessment. Accurate diagnosis is vital for the treatment planning of OSCC.

Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study.

Due to the rich ethnobotanical and growing evidence-based medicine records, the Alchemillae herba, i.e., the upper parts of the Lady's mantle (Alchemilla vulgaris L.), was used for the assessment of antimelanoma activity. The ethanolic extract of A. vulgaris strongly suppressed the viability of B16F1, B16F10, 518A2, and Fem-X cell lines. In contrast to the in vitro study, where the B16F1 cells were more sensitive to the treatment than the more aggressive counterpart B16F10, the results obtained in vivo using the corresponding syngeneic murine model were quite the opposite. The higher sensitivity of B16F10 tumors in vivo may be attributed to a more complex response to the extract compared to one triggered in vitro. In addition, the strong immunosuppressive microenvironment in the B16F1 model is impaired by the treatment, as evidenced by enhanced antigen-presenting potential of dendritic cells, influx and activity of CD4+ T and CD8+ T lymphocytes, decreased presence of T regulatory lymphocytes, and attenuation of anti-inflammatory cytokine production. All these effects are supported by the absence of systemic toxicity. A. vulgaris extract treatment results in a sustained and enhanced ability to reduce melanoma growth, followed by the restoration of innate and adopted antitumor immunity without affecting the overall physiology of the host.

The association between non-HDL cholesterol and high-grade pancreatic neuroendocrine neoplasms.

PURPOSE: High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). METHODS: A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. RESULTS: Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49). CONCLUSIONS: A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.

Updated endometrial cancer FIGO staging: the role of MRI in determining newly included histopathological criteria.

PURPOSE: Endometrial cancer (EC) is among the prevalent malignancies in gynecology, showing an increasing occurrence and mortality rate. The updated 2023 FIGO staging integrates both histopathological and molecular analyses, which significantly impact the prognosis and treatment approaches. This research aims to examine the effectiveness of MRI in identifying essential histopathological tumor features, including histological subtype, grade, and lymphovascular space invasion. METHODS: A total of 106 patients diagnosed with EC from February 2018 to December 2023 underwent preoperative pelvic MRI. Surgical procedures followed ESMO guidelines, with histopathological assessments using FIGO 2009 criteria. Two radiologists independently evaluated MRI images, measuring maximum tumor size, minimum tumor ADC value (using a free-hand ROI technique), and ADC tumor/myometrium ratio. MRI findings were compared with histopathological data. RESULTS: Peritoneal implant presence and tumor size exhibited significant differences between endometrioid adenocarcinoma (EAC) and non-endometrioid endometrial carcinoma (NEEC), with p values of < 0.001 and 0.003, respectively. Significant differences in age, tumor size, ADC tumor, and ADC tumor/myometrium between low-grade and high-grade tumors were observed, with p values of < 0.001, 0.004, 0.006, and 0.011, respectively. Increased tumor size, reduced ADC tumor, ADC tumor/myometrium, and pelvic peritoneal implant presence were significantly associated with LVSI, with p values of < 0.001, 0.001, 0.002, and 0.001, respectively. The AUC values for tumor size, ADC tumor, and ADC tumor/myometrium were 0.842, 0.781 and 0.747, respectively, in distinguishing between low and high-grade endometrial tumors. Similarly, obtained AUC values for predicting LVSI were 0.836, 0.719, and 0.696, respectively. CONCLUSION: Our study emphasizes MRI's role in predicting tumor characteristics such as histological subtype, grade, and LVSI based on updated FIGO criteria. By highlighting the potential of MRI, this research contributes to our comprehension of improving diagnostic and clinical management for EC. Further multicenter studies are warranted to validate these findings and establish MRI's role in EC management.

Sarcomatoid Dedifferentiation as a Predictor of Cancer-Specific Mortality in Surgically Treated Localized Renal Cell Carcinoma.

BACKGROUND: In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used. RESULTS: In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM. CONCLUSIONS: In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.

2012 Briganti nomogram predict prostate cancer progression in EAU intermediate risk with unfavorable tumor grade: A single center experience.

BACKGROUND: To investigate the potential prognostic impact of Briganti's 2012 nomogram in EAU intermediate-risk patients presenting with an unfavorable tumor grade and treated with robot-assisted radical prostatectomy, eventually associated with extended pelvic lymph node dissection. MATERIALS AND METHODS: From January 2013 to December 2021, the study included 179 EAU intermediate-risk patients presenting with an unfavorable tumor grade (ISUP 3), eventually associated with a PSA of 10-20 ng/ml and/or cT-2b. Briganti's 2012 nomogram was assessed as both a continuous and dichotomous variable, categorized according to the median (risk score ⩾7% vs <7%). Disease progression, defined as biochemical recurrence and/or metastatic progression, was evaluated using Cox proportional hazards in both univariate and multivariate analyses. RESULTS: Disease progression occurred in 43 (24%) patients after a median (95% CI) follow-up of 78 (65.7-88.4) months. The nomogram risk score predicted disease progression, evaluated both as a continuous variable (hazard ratio, HR = 1.064; 95% CI: 1.035-1.093; p < 0.0001) and as a categorical variable (HR = 3.399; 95% CI: 1.740-6.638; p < 0.0001). This association was confirmed in multivariate analysis, where hazard ratios remained consistent even after adjusting for clinical and pathological factors. CONCLUSIONS: In EAU intermediate-risk PCa cases presenting with an unfavorable tumor grade and treated surgically, Briganti's 2012 nomogram was associated with disease progression after surgery. Consequently, as the nomogram risk score increased, patients were more likely to experience PCa progression, facilitating the stratification of the patient population into distinct prognostic subgroups.

Prognostic Significance of Nuclear Factor Kappa B (p65) among Breast Cancer Patients in Cape Coast Teaching Hospital.

Breast cancer is the most prevalent cancer among African women, with high mortality rates in Ghana. Nuclear factor kappa B (NF-kB) has been associated with tumor progression in breast cancer. However, its clinical validation is controversial and understudied with no known published data on NF-kB (p65) among breast cancer patients in Ghana and other African countries. This study assessed the prognostic significance of NF-kB (p65) expression and its association with various clinicopathological features in breast cancer patients. Ninety formalin-fixed breast cancer tissues and 15 normal breast tissues were used to determine the expression of NF-kB (p65) using immunohistochemistry. We explored the correlation between expression of NF-kB (p65) and clinicopathological features. NF-kB (p65) was expressed in 86.7% of breast cancer tissues. There was a significant relationship between NF-kB (p65) expression and tumor grade, proliferation index (Ki67), and molecular subtype. High NF-kB (p65) expression in tumor grade 3 was about 10 times that of grade 1 (54.2% vs. 5.1%), and Ki67 > 20 was 79.7% compared to 20.3% for Ki67 ≤ 20. Patients with triple-negative breast cancer (TNBC) had 49.1% overexpression of NF-kB (p65) compared to 17%, 25.4%, and 8.5% for luminal A, luminal B, and HER2 cases, respectively. This study demonstrates that NF-kB (p65) was highly expressed among breast cancer patients at Cape Coast Teaching Hospital, Ghana, especially in TNBC. NF-kB (p65) could serve as a biomarker for cancer stage, progression, prognosis and as a therapeutic target.

Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma.

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa.

The effects of ANRIL polymorphisms on colorectal cancer, tumor stage, and tumor grade among Iranian population.

BACKGROUND: Colorectal cancer (CRC) is a type of neoplasm, developing in the colon or rectum. The exact etiology of CRC is not well known, but the role of genetic, epigenetic, and environmental factors are established in its pathogenesis. Therefore, the aim of this research was to explore the effects of ANRIL polymorphisms on the CRC and its clinical findings. METHODS AND RESULTS: The peripheral blood specimens were collected from 142 CRC patients and 225 controls referred to Milad Hospital, Tehran, Iran. PCR- RFLP method was used to analyze ANRIL rs1333040, rs10757274 rs4977574, and rs1333048 polymorphisms. The ANRIL rs1333040 polymorphism was related to a higher risk of CRC in the co-dominant, dominant, and log-additive models. ANRIL rs10757274, rs4977574, and rs1333048 polymorphisms showed no effect on CRC susceptibility. The CGAA and TGGA haplotypes of ANRIL rs1333040/ rs10757274/ rs4977574/rs1333048 polymorphisms were associated with the higher and the lower risk of CRC respectively. The rs1333040 polymorphism was associated with higher TNM stages (III and IV). The frequency of ANRIL rs10757274 polymorphism was lower in CRC patients over 50 years of age only in the dominant model. In addition, the rs10757274 was associated with well differentiation in CRC patients. CONCLUSION: The ANRIL rs1333040 polymorphism was associated with a higher risk of CRC and higher TNM stages. ANRIL rs10757274 polymorphism was associated with the well-differentiated tumor in CRC.

Impact of grade on workup of rectal neuroendocrine tumors: a retrospective cohort study : Grade impact on workup of rectal NETs.

BACKGROUND: Rectal neuroendocrine tumors (RNETs) are often discovered on screening colonoscopy. Indications for staging and definitive resection are inconsistent in current guidelines. We evaluated the role of grade in guiding staging and procedural decision-making. METHODS: Patients with biopsy confirmed RNETs between 2004 and 2015 were reviewed. Baseline characteristics, staging investigations (biochemical and imaging), and endoscopic/surgical treatment were recorded. Associations between grade, preoperative staging, interventions, and survival were determined using Fisher-Freeman-Halton Exact, log-rank, and Kaplan-Meier analysis. RESULTS: Amongst 139 patients with RNETs, 9% were aged ≥ 75 years and 44% female. Tumor grade was: 73% grade 1 (G1), 18%, grade 2 (G2) and 9% grade 3 (G3). Staging investigations were performed in 52% of patients. All serum chromogranin A and 97% of 24-hour urine 5-hydroxyindoleacetic acid tests were normal. The large majority of staging computed tomography (CT) scans were negative (76%) with subgroup analysis showing no G1 patients with CT identified distant disease compared with 38% of G2 and 50% of G3 patients (p < 0.001). G1 patients were more likely to achieve R0/R1 resections compared to G2 (95% vs. 50%, p < 0.001) and G1 patients had significantly better 5-year overall survival (G1: 98%, G2: 67%, G3: 10%, p < 0.001). CONCLUSION: Tumor grade is important in preoperative workup and surgical decision-making. Biochemical staging may be omitted but staging CT should be considered for patients with grade ≥ 2 lesions. Anatomic resections should be considered for patients with grade 2 disease.

Immunohistochemical study of CD74 biomarker in normal and malignant breast tissues.

OBJECTIVE: Aim: To detect the role of CD74 expression in breast carcinoma as a predictive marker for identifying the biological behavior of malignancy in Iraqi women.. PATIENTS AND METHODS: Materials and Methods: The study used technique of immunohistochemistry for detection CD74 protein role in breast cancer, and its expression in breast cancer tissue samples. Samples were collected in Al-Najaf city in Iraq, from Al-Forat Al-Awsat Oncology Center. The study was achieved at the Laboratories of the Faculty of Science in the University of Kufa. Fifty samples of breast cancer tissue, and twenty controls benign tissue were included in the study. The study has investigated relationship between expression of biomarker with grade, age of patient and tumor size. RESULTS: Results: The study showed that the cytoplasmic expression of CD74 with more clear and intensive staining in the cytoplasm, and reported that CD74 positivity rate was 52%. A significant association between CD74 expression and grade and size of tumor, so CD74 can be considered as a biomarker for prediction of breast cancer in women. No association was found between CD74 expression and each of patients' age and node metastasis. CONCLUSION: Conclusions: The study represents an important step in our region because there are a few studies about this topic; more efforts are required to approve the function of this biomarker.

Uterine adenosarcoma: Clinical significance of histological classification and SNP array analysis.

Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is known about the molecular heterogeneity of these tumors. In this study, we aim to reclassify a large retrospective monocentric cohort of uterine adenosarcomas according to tumor grade and SO, to evaluate the clinical significance of pathological classification and to correlate with copy-number variations inferred from single nucleotide polymorphism array. Of the 67 uterine adenosarcomas, 18 (26.9%) were low grade without SO, 7 (10.4%) low grade with SO, 8 (11.9%) high grade without SO and 34 (50.7%) high grade with SO. SO, necrosis and RMS were more frequent in high grade than low grade adenosarcomas (p < 0.001). Low-rank test showed that recurrence-free survival was significantly shortened in high grade than low grade adenosarcomas (p = 0.035) and SO was associated with shortened overall and recurrence-free survival (p = 0.038 and p = 0.009, respectively). High-grade tumors displayed complex genomic profiles with multiple segmental losses including TP53, ATM and PTEN genes. The median genomic index was significantly higher in high grade than low grade tumors (27 [3-60] vs 5,3 [0-16], p < 0.0001) and was significantly higher in presence of SO in low grade tumors (12,8 [10-16] vs 2,6 [0-10], p = 0.0006). We propose to report sarcomatous overgrowth with the tumor grade for prognostication in adenosarcoma and representative sampling is crucial for evaluation of these histological criteria.

El papel del antígeno prostático específico (PSA) y el estadio patológico antes de la radioterapia en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con recidiva del cancer de próstata tras prostatectomía radical / Role of PSA levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy

Objetivo Evaluar el valor del antígeno prostático específico (PSA) en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con cáncer de próstata (CaP) de alto (puntuación de Gleason≥8, pT≥3, pN1) y bajo grado (puntuación de Gleason<8, pT<3, pN0). Materiales y métodos Ciento ochenta y ocho pacientes se sometieron a una RMmp de 1,5-T después de la prostatectomía radical y antes de la radioterapia. Los pacientes se dividieron en 2 grupos: el grupo A incluía pacientes con recidiva bioquímica (RB) y el grupo B pacientes sin RB pero con alto riesgo de recidiva local. Teniendo en cuenta la puntuación de Gleason, pT y pN como variables de agrupación independientes, se realizaron análisis ROC de los niveles de PSA en el momento del diagnóstico del CaP primario y antes de la radioterapia con el fin de identificar el punto de corte óptimo para predecir el resultado de la RMmp. Resultados En los grupos A y B, el área bajo la curva del PSA antes de la radioterapia fue superior a la del PSA en el momento del diagnóstico del CaP, en tumores de bajo y alto grado. Para los tumores de bajo grado, la mejor área bajo la curva fue de 0,646 y 0,685 en el grupo A y B, respectivamente; para los tumores de alto grado, la mejor área bajo la curva fue de 0,705 y 1 en el grupo A y B, respectivamente. Para los tumores de bajo grado, el punto de corte óptimo del PSA fue de 0,565-0,58ng/ml en el grupo A (sensibilidad y especificidad: 70,5% y 66%), y de 0,11-0,13ng/ml en el B (sensibilidad y especificidad: 62,5% y 84,6%). Para los tumores de alto grado, el punto de corte de PSA óptimo fue de 0,265-0,305ng/ml en el grupo A (sensibilidad y especificidad: 95% y 42,1%), y de 0,13-0,15ng/ml en el grupo B (sensibilidad y especificidad: 100%). Conclusión La RMmp se debe realizar como herramienta diagnóstica complementaria siempre que se detecte una RB, especialmente en el CaP de alto grado... (AU)

Objective To evaluate prostate-specific antigen (PSA) value in multiparametric magnetic resonance imagin (mp-MRI) results prediction, analyzing patients with high (Gleason Score ≥8, pT≥3, pN1) and low grade (Gleason Score <8, pT<3, pN0) prostate cancer (PCa). Materials and methods One hundred eighty-eight patients underwent 1.5-T mp-MRI after radical prostatectomy and before radiotherapy. They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score, pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before radiotherapy were performed in order to identify the optimal cut-off to predict mp-MRI result. Results Group A and B showed higher area under the curve for PSA before radiotherapy than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best area under the curve was 0.646 and 0.685 in group A and B; for high grade the best area under the curve was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/ml in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/ml in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/ml in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/ml in B (sensitivity, specificity: 100%). Conclusion Mp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/ml. (AU)

Immunohistochemical and molecular evaluation of TUSC2 expression in breast cancer.

OBJECTIVE: Tumor suppressor candidate 2 has shown to be deleted in lung, colon, and bladder cancer types. In the present study, we aimed to investigate the expression of TUSC2 in breast cancer. MATERIALS AND METHODS: A total of thirty patients with breast cancer were included in the study. Normal and tumor tissue samples from fresh mastectomy materials were stored at -80 C until the number of cases was completed for gene expression analysis. Histopathological examination was carried out with routine hematoxylin & eosin method. TUSC2 staining was performed for immunohistochemical analysis. RESULTS: The tumors of thirteen patients were Luminal A, fourteen patients were Luminal B, one patient was cerbB2(+), and tumors of two patients were triple-negative. Ki67 proliferation index was less than 14% in fifteen cases and tumor size was less than 2 cm in seven cases. Lymphovascular invasion and lymph node metastasis were present in thirteen cases. Statistically, TUSC2 expression significantly decreased or was lost in breast tumor tissues compared to normal tissues (p < 0.0001). TUSC2 expression decreased as the Ki67 proliferation index increased (p = 0.0003), and TUSC2 expression decreased as tumor size increased (p = 0.0483). The loss or decrease in the TUSC2 expression was significant as the tumor grade increased (p = 0.3740). Gene expression analysis correlated with immunohistochemistry results. CONCLUSION: The results of the present study demonstrated a decrease or loss of TUSC2 expression in breast cancer tissue compared to normal tissue. A correlation was found between TUSC2 expression and Ki67 proliferation index and tumor size.

Impact of [11C]methionine PET with Bayesian penalized likelihood reconstruction on glioma grades based on new WHO 2021 classification.

OBJECTIVE: The uptake of [11C]methionine in positron emission tomography (PET) imaging overlapped in earlier images of tumors. Bayesian penalized likelihood (BPL) reconstruction increases the quantitative values of tumors compared with conventional ordered subset-expectation maximization (OSEM). The present study aimed to grade glioma malignancy based on the new WHO 2021 classification using [11C]methionine PET images reconstructed using BPL. METHODS: We categorized 32 gliomas in 28 patients as grades 2/3 (n = 15) and 4 (n = 17) based on the WHO 2021 classification. All [11C]methionine images were reconstructed using OSEM + time-of-flight (TOF) and BPL + TOF (ß = 200). Maximum standardized uptake value (SUVmax) and tumor-to-normal tissue ratio (T/Nmax) were measured at each lesion. RESULTS: The mean SUVmax was 4.65 and 4.93 in grade 2/3 and 6.38 and 7.11 in grade 4, and the mean T/Nmax was 7.08 and 7.22 in grade 2/3 and 9.30 and 10.19 in grade 4 for OSEM and BPL, respectively. The BPL significantly increased these values in grade 4 gliomas. The area under the receiver operator characteristic (ROC) curve (AUC) for SUVmax was the highest (0.792) using BPL. CONCLUSIONS: The BPL increased mean SUVmax and mean T/Nmax in lesions with higher contrast such as grade 4 glioma. The discrimination power between grades 2/3 and 4 in SUVmax was also increased using [11C]methionine PET images reconstructed with BPL.