Tumor Histological Differentiation Research Articles

Tumor Location Is an Independent Prognostic Factor in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer: A Multicenter Retrospective Study.

Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of survival for patients with completely resected pathological stage I NSCLC. This was a multicenter retrospective study conducted in Taiwan. Included patients were diagnosed with stage I NSCLC and had undergone primary tumor resection. Variables including tumor location, pathological stage, histological differentiation, and International Association for the Study of Lung Cancer (IASLC) grade were evaluated for predictive ability for disease-free survival (DFS) and overall survival (OS). A total of 208 patients were included, with 123 (59.1%) patients having a primary tumor in the upper and middle lobes. The median duration of follow-up for survivors was 60.5 months. Compared to patients with IASLC Grade 3 disease, patients with Grade 1 disease had significantly longer DFS. Tumor location and IASLC grade were independent predictors for OS in multivariate analysis. Specifically, patients with NSCLC in the lower lobe and patients who are histologically classified as IASLC Grade 3 may have poorer prognosis and require greater attention to improve outcomes.

Expression of E-Cadherin and N-Cadherin in the Endocervix as a Predictive Factor in Patients with Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecological malignancy. This study aimed to evaluate the expression of E-cadherin and N-cadherin in primary endometrial lesions and the endocervix in patients with EC to identify noninvasive predictive factors. In this single-center retrospective study, data on 101 patients who underwent surgery for EC were collected. The immunohistochemical expression of E-cadherin and N-cadherin was assessed depending on the tumor grade, location, and cell differentiation. Correlations between E-cadherin and N-cadherin levels in the endocervix and the primary tumor were determined. The degree of histological tumor differentiation significantly affected E-cadherin expression (p = 0.04) but had no impact on N-cadherin levels. In type II EC, the expression of both cadherins in the tumor tissue differed from their endocervical levels. The expression of E-cadherin differed significantly between the endocervix (p < 0.001) and the tumor (p = 0.001), depending on the type of EC. The expression of E-cadherin was related to the N-cadherin level only in the endocervix in patients with type II EC (p = 0.02). E-cadherin and N-cadherin were expressed in the endocervix in patients with EC. The expression of cadherins, determined during cervical cytology, may be a valuable clinical marker of EC.

A prediction nomogram for perineural invasion in colorectal cancer patients: a retrospective study

BackgroundPerineural invasion (PNI), as the fifth recognized pathway for the spread and metastasis of colorectal cancer (CRC), has increasingly garnered widespread attention. The preoperative identification of whether colorectal cancer (CRC) patients exhibit PNI can assist clinical practitioners in enhancing preoperative decision-making, including determining the necessity of neoadjuvant therapy and the appropriateness of surgical resection. The primary objective of this study is to construct and validate a preoperative predictive model for assessing the risk of perineural invasion (PNI) in patients diagnosed with colorectal cancer (CRC).Materials and methodsA total of 335 patients diagnosed with colorectal cancer (CRC) at a single medical center were subject to random allocation, with 221 individuals assigned to a training dataset and 114 to a validation dataset, maintaining a ratio of 2:1. Comprehensive preoperative clinical and pathological data were meticulously gathered for analysis. Initial exploration involved conducting univariate logistic regression analysis, with subsequent inclusion of variables demonstrating a significance level of p < 0.05 into the multivariate logistic regression analysis, aiming to ascertain independent predictive factors, all while maintaining a p-value threshold of less than 0.05. From the culmination of these factors, a nomogram was meticulously devised. Rigorous evaluation of this nomogram's precision and reliability encompassed Receiver Operating Characteristic (ROC) curve analysis, calibration curve assessment, and Decision Curve Analysis (DCA). The robustness and accuracy were further fortified through application of the bootstrap method, which entailed 1000 independent dataset samplings to perform discrimination and calibration procedures.ResultsThe results of multivariate logistic regression analysis unveiled independent risk factors for perineural invasion (PNI) in patients diagnosed with colorectal cancer (CRC). These factors included tumor histological differentiation (grade) (OR = 0.15, 95% CI = 0.03–0.74, p = 0.02), primary tumor location (OR = 2.49, 95% CI = 1.21–5.12, p = 0.013), gross tumor type (OR = 0.42, 95% CI = 0.22–0.81, p = 0.01), N staging in CT (OR = 3.44, 95% CI = 1.74–6.80, p < 0.001), carcinoembryonic antigen (CEA) level (OR = 3.13, 95% CI = 1.60–6.13, p = 0.001), and platelet-to-lymphocyte ratio (PLR) (OR = 2.07, 95% CI = 1.08–3.96, p = 0.028).These findings formed the basis for constructing a predictive nomogram, which exhibited an impressive area under the receiver operating characteristic (ROC) curve (AUC) of 0.772 (95% CI, 0.712–0.833). The Hosmer–Lemeshow test confirmed the model's excellent fit (p = 0.47), and the calibration curve demonstrated consistent performance. Furthermore, decision curve analysis (DCA) underscored a substantial net benefit across the risk range of 13% to 85%, reaffirming the nomogram's reliability through rigorous internal validation.ConclusionWe have formulated a highly reliable nomogram that provides valuable assistance to clinical practitioners in preoperatively assessing the likelihood of perineural invasion (PNI) among colorectal cancer (CRC) patients. This tool holds significant potential in offering guidance for treatment strategy formulation.

Patient metabolic profile defined by liver and muscle 18F-FDG PET avidity is independently associated with overall survival in gastric cancer.

PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care. Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUVmean of liver to the average SUVmean of the bilateral rectus femoris muscles. Kaplan-Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS. Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65years, and 146 (73%) were male. On univariate analysis, rectus femoris PET-CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56-0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009). Elevated LRF ratio, a patient-specific PET-CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer.

MicroRNA-34, microRNA-130, microRNA-148, microRNA-181, microRNA-194 and microRNA-605 expression in colon cancer tissue

Purpose of the study. Determination of the expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 in colon tumor tissue depending on the clinical and morphological features of the tumor and the effectiveness of treatment.Materials and methods. The study included 56 patients diagnosed with colorectal cancer aged 43 to 75 years with the average age of 54 years. Taking into account the local prevalence of the process patients received surgical or combined treatment, including neoadjuvant chemotherapy, in the clinics of the Cancer Research Institute, Tomsk NRMC. MicroRNA expression was determined by polymerase chain reaction (PCR) in real time.Results. The obtained information revealed the relation of microRNA‑130 to the tumor size. The development of regional metastases was associated with changes in microRNA‑130, microRNA‑194 and microRNA‑605. The level of histological organization of the tumor was associated with microRNA‑34, microRNA‑130, microRNA‑148, and the response to therapy – with microRNA‑130, microRNA‑148 and microRNA‑605. In addition, according to the study, the significance of microRNA‑130 was revealed, which is associated with tumor spread, histological differentiation and response to antitumor therapy.Conclusion. The features of expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 associated with clinical and morphological features of colon tumors were revealed. Correlations between the studied indicators are noted, which probably determine the outcome and prognosis of the disease.

The Clinical Implication of Conversion Surgery in Patients with Stage IV Gastric Cancer Who Received Systemic Chemotherapy.

With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers-HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren's classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates.

Primary Bladder Sarcoma: A multi-institutional experience from the Rare Cancer Network.

Primary sarcoma of the urinary bladder (SUB) is a rare but aggressive form of bladder cancer (BCa). Available evidence on SUB is limited to case reports and small series. The aim of the present multi-institutional study was to assess the clinical features, treatments, and outcomes of patients with SUB. Using a standardized database, 7 institutions retrospectively collected the demographics, risk factors, clinical presentation, treatment modalities and follow-up data on patients with SUB between January 1994 and September 2021. The main inclusion criteria included BCa with soft tissue tumor histology and sarcomatoid differentiation. Fifty-three patients (38 men and 15 women) were identified. Median follow-up was 18 months (range 1-263 months). Median age at presentation was 69 years (range 16-89 years). Twenty-six percent of patients had a prior history of pelvic radiotherapy (RT), and 37% were previous smokers. The main presenting symptoms at diagnosis were hematuria (52%), pelvic pain (27%), and both hematuria and pelvic pain (10%). American Joint Committee on Cancer (AJCC) 8 th edition stage II, III and IV at diagnosis were 21%, 63% and 16%, respectively. Treatment modalities included surgery alone (45%), surgery plus neo- or adjuvant-chemotherapy (17%), surgery plus neo- or adjuvant-RT (11%), RT with concurrent chemotherapy (4%), neo-adjuvant chemotherapy plus surgery plus adjuvant RT (2%) and palliative treatment (21%). Rates of local and distant recurrences were 49% and 37%, respectively. Five-year overall survival and progression-free survival (PFS) were 66.5% and 37.6%, respectively. No statistically significant differences in PFS between the treatment modalities were observed. Primary SUB is a heterogeneous disease group, commonly presenting at advanced stages and exhibiting aggressive disease evolution. In contrast to urothelial carcinoma, the primary pattern of recurrence of SUB is local, suggesting the need for multimodal approaches. Continuous international collaborative efforts seem warranted to provide guidance on how to best tailor treatments based on SUB-specific indices.

Evaluation of serum levels of soluble (s)L- and (s)P-selectins in endometrial cancer.

A number of reports on the role of selectin in the process of carcinogenesis, at the stage of proliferation and metastasis, have been available. The aim of the study was to analyze (s)P- and (s)L-selectin serum concentrations in women with EC and to compare these concentrations to clinical/pathological parameters and disease progression using surgical-pathological staging data. A total of 46 patients with EC and 50 healthy controls were included in the study. Serum concentrations of sL- and sP-selectins were measured in all participants. The oncologic protocol was implemented in all women from the study group. Significantly higher serum concentrations were found in EC women as compared to controls. No statistically significant differences were found between the concentrations of the soluble forms of selectins and the following parameters: histologic type of EC, histologic tumor differentiation, depth of myometrial infiltration, cervical involvement, distant metastases, vascular space invasion, and disease advancement. Slightly higher (s)P-selectin concentrations were observed in serous carcinoma, in women with cervical involvement, in the sera of women with vascular space invasion and with advanced stages of the disease. Slightly higher mean (s)P-selectin concentrations correlated with lower differentiation of the tumor. Slightly higher mean (s)P-selectin concentration was detected in the sera of women with lymph node metastases and with the serosal and/or adnexal involvement. The results were statistically insignificant, but they almost reached statistical significance. L- and P-selectins play a role in the biology of EC. The absence of an unambiguous relationship between differences in (s)L- and (s)P-selectin levels and disease advancement suggests that they do not play a vital role in tumor progression in endometrial cancer.

Comparative Analyses of the Clinicopathologic Features of Short-Term and Long-Term Survivors of Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreatoduodenectomy.

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.

CORRELATION BETWEEN BRANDWEIN-GENSLER'S HISTOLOGIC RISK MODEL AND BRODER'S HISTOLOGICAL GRADING IN ORAL SQUAMOUS CELL CARCINOMAS

Introduction: Several clinicopathological and molecular factors have been used to prognosticate and predict outcomes in the patients of oral squamous cell carcinomas (OSCC). Many histological grading systems have been described, however there is a lack of agreement as to a satisfactory robust predictive model. The Brandwein-Gensler risk model has been validated in various multicentre studies as a reliable prognostic model for advanced as well as early disease. The Broders grading system, still recommended by WHO, is probably the best-known attempt at prognostication with subjective assessment of key histological features. This study was conducted to evaluate various histological prognostic markers in case of Oral Squamous Cell Carcinomas (OSCC) and understand their correlation with each other. Total 66 Materials and Methods: excised specimens of Oral squamous cell carcinomas were retrospectively analysed and Histologic risk scoring was done according to the Histologic risk model (HRM) given by Brandwein-Gensler et al. Broder's histological grading was done on the basis of differentiation of tumor. Results: Histological grading of tumor based on differentiation of tumor shows poor correlation with Brandwein-Gensler's Histologic risk model with a sensitivity and specicity of 34.7% and 52.9% respectively; inferring that differentiation status of tumor is not a good parameter for prognostic evaluation of Oral Squamous Cell Carcinomas. However, owing to the fact that no poorly differentiated tumor was noted in the current study, further evaluation and large sample size is required to conrm. Researc Conclusion: h on predictive and prognostic biomarkers has ignited hope for individualizing therapy to facilitate better survival and reduce overtreatment in the patients of oral SCC. There is no signicant association between differentiation of tumor and WPOI. No signicant correlation exists between differentiation of tumor and Histologic risk model scoring thereby inferring that histological differentiation of tumor is not a good prognostic parameter.

Host and primary tumor factors for the development of multiple cutaneous squamous cell carcinomas among a retrospective cohort in Rhode Island

Risk factors for a primary cutaneous squamous cell carcinoma (CSCC) are well-established; however, the host and primary tumor risk factors for subsequent CSCC have not been fully explored. We performed a retrospective chart review of patients diagnosed with CSCC in an academic dermatology clinic in Rhode Island from 2016-2019. Logistic regression was used to evaluate the associations between host factors and multiple CSCC and between primary tumor characteristics and the risk of subsequent CSCC. Adjusted odds ratios (aORs) and 95% CIs were calculated. A total of 1312 patients with CSCC diagnoses were included. Host risk factors significantly associated with multiple CSCCs included: aged >80years (aOR, 2.18; 95% CI, 1.46-3.31); history of: solid organ transplant (aOR, 2.41; 95% CI, 1.20-4.80); skin cancer (aOR, 1.96; 95% CI, 1.52-2.54); other cancer (aOR, 1.49; 95% CI, 1.11-2.00); family history of skin cancer (aOR, 1.36; 95% CI, 1.03-1.78); and actinic keratosis (aOR, 1.52; 95% CI, 1.18-1.95). Tumor location, diameter, histologic differentiation, and treatment were not significant predictors of subsequent CSCCs. Study patients were predominantly White and from a single institution, limiting the generalizability of results. Certain host characteristics were associated with the development of subsequent CSCC, which may inform clinical guidelines for follow-up.

CT-based radiomics with various classifiers for histological differentiation of parotid gland tumors.

This study assessed whether radiomics features could stratify parotid gland tumours accurately based on only noncontrast CT images and validated the best classifier of different radiomics models. In this single-centre study, we retrospectively recruited 249 patients with a diagnosis of pleomorphic adenoma (PA), Warthin tumour (WT), basal cell adenoma (BCA) or malignant parotid gland tumours (MPGTs) from June 2020 to August 2022. Each patient was randomly classified into training and testing cohorts at a ratio of 7:3, and then, pairwise comparisons in different parotid tumour groups were performed. CT images were transferred to 3D-Slicer software and the region of interest was manually drawn for feature extraction. Feature selection methods were performed using the intraclass correlation coefficient, t test and least absolute shrinkage and selection operator. Five common classifiers, namely, random forest (RF), support vector machine (SVM), logistic regression (LR), K-nearest neighbours (KNN) and general Bayesian network (Gnb), were selected to build different radiomics models. The receiver operating characteristic curve, area under the curve (AUC), accuracy, sensitivity, specificity and F-1 score were used to assess the prediction performances of these models. The calibration of the model was calculated by the Hosmer-Lemeshow test. DeLong's test was utilized for comparing the AUCs. The radiomics model based on the RF, SVM, Gnb, LR, LR and RF classifiers obtained the highest AUC in differentiating PA from MPGTs, WT from MPGTs, BCA from MPGTs, PA from WT, PA from BCA, and WT from BCA, respectively. Accordingly, the AUC and the accuracy of the model for each classifier were 0.834 and 0.71, 0.893 and 0.79, 0.844 and 0.79, 0.902 and 0.88, 0.602 and 0.68, and 0.861 and 0.94, respectively. Our study demonstrated that noncontrast CT-based radiomics could stratify refined pathological types of parotid tumours well but could not sufficiently differentiate PA from BCA. Different classifiers had the best diagnostic performance for different parotid tumours. Our study findings add to the current knowledge on the differential diagnosis of parotid tumours.

Tumor budding as an indicator for lymph node metastasis and prognosis of early gastric cancer.

Tumor budding, considered as an independent risk factor reflecting prognosis of some malignant tumors, has been recognized as an important clinicopathological indicator of colorectal carcinoma. However, the evaluation of tumor budding and its clinicopathological significance in gastric cancer remain controversial. To investigate the relationship between tumor budding and clinical biological behavior of early gastric cancer (EGC) and assess the predictive value of tumor budding for lymph node metastasis as well as its impact on prognosis of EGC patients. Tissue specimens of 164 EGC patients who underwent radical gastrectomy between June 2011 and January 2017 from a single center were selected to carry out HE and CK staining respectively, so as to evaluate tumor budding under light microscopy. Clinicopathological data and follow-up results of all EGC patients were collected for statistical analysis among tumor budding, EGC clinicopathological factors and prognosis. Of all 164 EGC patients, there were 84 (51.2%) cases with mucosal invasion and 80 (48.8%) cases with submucosal invasion. Meanwhile, 32 cases (19.5%) had lymph node metastasis, 19 (11.6%) had lympho-vascular invasion and 4 (2.4%) had early recurrence. Tumor budding were observed in 90 (54.9%) patients, with low-grade budding 68 (41.5%) cases and high-grade budding 22 (13.4%) cases. Tumor budding was closely correlated with tumor size (c2 = 6.609, P = 0.037), tumor histologic differentiation (c2 = 10.522, P = 0.032), depth of invasion (c2 = 8.787, P = 0.012), lymph node metastasis (c2 = 24.226, P < 0.01), TNM stage (c2 = 24.226, P < 0.01), lympho-vascular invasion (c2 = 8.225, P = 0.016) and early recurrence (c2 = 6.462, P = 0.040). Additionally, tumor budding was correlated with postoperative survival rate as well. Multiple regression analysis revealed that tumor budding was an independent influencing factor of postoperative 3-year survival rate, 5-year survival rate, OS, DFS and DSS (P < 0.05). Furthermore, tumor budding was an independent risk factor of lymph node metastasis of EGC patients, and high-grade budding was a high-risk indicator of lymph node metastasis. Tumor budding is related to tumor size, tumor histologic differentiation, depth of invasion, lymph node metastasis, lympho-vascular invasion and early recurrence of EGC. Tumor budding, especially high-grade budding can serve as an indicator for predicting lymph node metastasis of EGC, and high-grade budding could be an important parameter for evaluating prognosis of EGC patients.

Mixed Histologic Type is a Risk Factor for Lymph Node Metastasis in Submucosal Invasive Early Gastric Cancer

IntroductionThe treatment regimen for early gastric cancer (EGC) with mixed histologic type remains controversial. We aimed to clarify the relationship between mixed histologic type and lymph node metastasis (LNM) in EGC, with emphasis on submucosal invasive EGC. MethodsWe collected data on 730 consecutive EGC patients at Nanjing Drum Tower hospital between June 2010 and May 2019. Risk factors of LNM and overall survival were analyzed to compare the prognostic differences between different histologic types. ResultsMixed-type EGC patients had higher LNM rates than differentiated-type patients (29.2 % versus 10.6 %, P < 0.001), while no significant difference was found between mixed-type and undifferentiated-type EGC patients (29.2% versus 24.0%, P = 0.225). Multivariate analyses identified tumor location (cardiac and bottom versus antrum), larger tumor size, submucosal invasion, histologic differentiation (undifferentiated-type, mixed-type versus differentiated-type), and lymphovascular invasion as independent risk factors for LNM in EGC patients. Subgroup analysis further elucidated that mixed histologic type was associated with LNM in submucosa invasive EGC, but not in mucosa-confined EGC. There was no statistical significance in overall survival and disease-specific survival of submucosal invasive EGC patients who underwent radical gastrectomy with lymphadenectomy between different histologic types (P = 0.151). ConclusionsMixed histologic type may be an independent risk factor for LNM in submucosal invasive EGC. Curative resection with lymphadenectomy should be considered the appropriate treatment for submucosal invasive EGC with mixed histologic type.

Imaging of pre- and post-cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pediatric intraperitoneal malignancy.

Although rare, pediatric peritoneal carcinomatosis does occur in primary abdominopelvic tumors. Additionally, peritoneal carcinomatosis has been described to occur as metastatic disease where the primary tumor is outside the abdominopelvic cavity. Where amenable, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can be beneficial in disease management. However, favorable outcomes are predicated on specific tumor histology as well as proper patient selection, which significantly relies on preoperative imaging. This review gives a comprehensive, up-to-date summary on pediatric peritoneal carcinomatosis pre-surgical evaluation; where imaging is beneficial and limited; pediatric radiologists' role in helping to quantify disease; and how we, as pediatric radiologists, can help the surgeons and oncologists in the selection of patients for cytoreductive surgery and HIPEC.

Up regulation of long non-coding RNAs BACE1 and down regulation of LINC-PINT are associated with CRC clinicopathological characteristics

BackgroundLong non-coding RNAs (LncRNAs) are known to have regulatory consequences for aberrant gene expression in cancers. The aim of this study was to evaluate the expression levels of long non-encoding RNAs, BACE1 (β-secretase1) and LINC-PINT (Long Intergenic Non-Protein Coding RNA, P53 Induced Transcript), in colorectal cancer (CRC) with clinicopathological parameters.Methods and resultsBioinformatics analysis defining effectual signalling pathways Wnt. A total of 130 tissue samples (50 fresh CRC tissues with parallel adjacent normal tissues (ADJ) accompanied with 30 normal healthy control tissue samples) were collected from the Iranian population. mRNA expression analysis was performed via Real Time Q-PCR. Statistical analysis for comparing CRC expression levels with ADJ and normal healthy tissues were carried out using Kruskal–Wallis tests. The Receiver Operating Characteristic (ROC) curve was plotted for each LNC, separately. We discovered that PINT and BACE1 expression levels were decreased and increased respectively in CRC tumour samples compared with ADJ normal and healthy tissues. Clinicopathological parameter assessment revealed a significant relationship between PINT expression, tumour location, staging and distant metastasis (p < 0.009, p < 0.014, p < 0.008, respectively). Also, BACE1 over expression was significantly associated with tumour site (p < 0.009), metastasis (p < 0.017) and histological differentiation (p < 0.028) and staging (p < 0.017). Furthermore, ROC curve plotting showed LINC-PINT LNC-BACE1 may distinguish between early and late-stage of CRC, highlighting the value of both BACE1 and PINT as CRC progression biomarkers.ConclusionWe investigated two LNCRNAs (PINT and BACE1) as potential CRC prognostic biomarkers, which are imperative for early and effective medical intervention in CRC. Expression levels of PINT and BACE1 in CRC tissue samples may serve to identify metastasis earlier, increasing patient survival rates and expediating clinical treatment options.

HAEMATOLOGICAL PARAMETERS AND THEIR SIGNIFICANCE IN PREDICTING SEVERITY IN TERMS OF TUMOR GRADE IN PATIENTS WITH ORAL SQUAMOUS CELL CARCINOMA

Objective: The objective of our study was to determine the most reliable haematological parameters for assessing the tumor severity with respect to histological grade in patients with Oral Squamous Cell Carcinoma. Material and Methods: This retrospective cross-sectional study was conducted at Pathology Department, Pakistan Institute of Medical Sciences, Islamabad from January to December 2019. Fifty-eight patients of Oral Squamous Cell Carcinoma were selected by consecutive non-probability sampling. Preoperative hemogram values including total leukocyte count, red cell count, hematocrit, hemoglobin, red cell indices, platelet count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were recorded and was studied how these parameters differed among the histological grades of tumor. Stratification of patients was done based on gender and histological grade of tumor. Independent-sample t-test for gender and ANOVA-test for histological grade was applied to assess differences in haematological parameter measurements between the groups. P&lt; 0.05 was considered significant. Results: Anemia was observed as a common finding in our patients seen in 24% cases. Mean platelet count was within normal range. We observed that the haematological parameters i.e. total leukocyte count, absolute neutrophil count, absolute lymphocyte count, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio varied significantly with the advancing grades of the tumor from well-differentiated to poorly-differentiated keratinizing oral squamous cell carcinoma. Conclusion: The pre-surgical haematological profile holds many prognostic indicators, useful in predicting tumor severity in terms of histological differentiation of tumor. Key Words: Oral squamous cell carcinoma, Prognosis, Histology

COX2 Effects on endometrial carcinomas progression

Uterine corpus cancer is one of the most prevalent gynecologic malignancies, among which endometrial cancers (EC) represent about 90 %. Despite the proven predictive value of several immunohistochemical markers, there remains a need to identify new indicators of EC progression and exploit them for therapeutic purposes. Potential candidates with diagnostic and therapeutic efficacy include cyclooxygenases (COXs). We studied 50 EC cases: 30 endometrioid (EEC), 10 serous (SEC), 10 clear-cell endometrial carcinomas (CCEC) and 10 cases of normal endometrial tissues. We investigated the expression of COX2, ER, PR, Ki-67, EGFR, p53, Bcl-2, VEGF, MMP1, CD31, and CD163 immunohistochemically. COX2 levels in EC tissue are elevated compared to the normal endometrium and depend on tumour histological features and differentiation. Elevated COX2 leads to increased tumour cell proliferation, apoptosis inhibition, increased VEGF expression, microvessel density, and M2 macrophage infiltration, and inhibition of PR expression. ER, EGFR, and MMP1 levels are unaffected by COX2, whose levels are independent of patient age and FIGO stage

Molecular parameters impacting the success rate of a lung cancer PDX model.

e20592 Background: Patient-derived xenograft (PDX) models can provide renewable cancer tissue resources, are being increasingly utilized for the molecular characterizations of cancers and preclinical studies on drug activities, and have the potential to advance biomarker identification. Previous research has demonstrated that PDX tumors preserve the histologic and morphologic characteristics and gene expression and mutation patterns of primary tumors, and correlate to patient survival. Tumor histological subtypes and differentiation grades are known to contribute to the success of PDX intake, but little is known about how molecular features associate with the success of PDX engraftment or whether PDX preserves subclonal architecture of primary tumors. Methods: To fill this void, we analyzed 252 primary tumor samples from the SPORE/ICON project at MD Anderson Cancer Center that were used for generating PDXs and had comprehensive genomic, transcriptomic, and immune profiling data available to evaluate the parameters impacting the intake success of lung cancer PDXs. In order to establish the impact of molecular features on PDX intake success we also assessed the fidelity of PDX in representing the molecular features of this cohort of primary tumors. Results: Only 36% of the primary tumors in this study successfully generated a PDX, with Squamous Cell Carcinoma PDX demonstrating an intake rate of 67% and Adenocarcinoma PDX demonstrating an intake rate of 21%. Genomic architecture derived from whole exome sequencing showed not only 43% (38-48%) of mutations shared, but also similar clonal architecture between primary tumors and PDX. Higher copy number aberration burden, high tumor purity and low immune infiltration in primary tumors were found to be associated with successful intake of PDX. Transcriptomics revealed 6,103 genes differentially expressed between primary tumors with successful PDX intake versus those which were unsuccessful. Pathway analysis of these genes indicated that inhibition of cell proliferation, signaling, and migration as well as DNA replication, recombination and repair were associated with PDX intake failure regardless of histology. Conclusions: These findings indicate that PDX intake success is regulated by molecular features and multiomic evaluation of lung cancer primary tumors can be used as a marker for determining which samples to use for PDX model generation.

Immune Microenvironment of Muscular-Invasive Urothelial Carcinoma: The Link to Tumor Immune Cycle and Prognosis.

In this study, we investigated the relationship between the tumor immune microenvironment (TIME), histological differentiation and hypoxia in patients with muscular-invasive urothelial carcinomas (MIUC) after radical cystectomy. Forty-two cases of pT2-3N0M0 MIUCs underwent clinical, histological and immunohistochemical evaluation by counting CD8+, FOXP3+, CD68+, CD163+ cells and polymorphonuclear leukocytes (PMN) in intra-tumoral and peritumoral areas, assessing PD-L1 and GLUT1 expression for defining the impact of tumor immune contexture on patients’ outcomes. Five-year survival rates and overall survival were calculated. Most of the MIUCs demonstrated the immune-desert or immune-excluded TIME, reflecting altered mechanisms of T-cells’ activation or traffic into tumors. Tumor immune contexture was closely related to histological differentiation. CD8+ cells were scant in MIUCs with papillary and squamous differentiation, while basal-like or mesenchymal-like histological differentiation was associated with increased density of CD8+ cells. A high rate of PD-L1 expression (47.6%) was not related to immune cell infiltration. M2-macrophages predominated under CD8+ lymphocytes. The abundance of PMN and CD163+ macrophages in MIUCs was associated with high GLUT1 expression. CD8+, CD68+, FOXP3+ cells and PD-L1 status did not affect patients’ outcomes, while high CD163+ density and PMN infiltration were associated with the unfavorable outcome of patients with MIUC. These data drive the hypothesis that in MIUC, immune escape mechanisms are shifted towards the role of the innate immunity cells rather than CD8+ lymphocytes’ functioning.