Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers.

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme's association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients.

Cytochrome 4Z1 Expression is Associated with Poor Prognosis in Colon Cancer Patients.

PURPOSE: Colon cancer is a leading cause of mortality worldwide. It has a relatively poor prognosis; therefore, new therapies are needed. One of the tumour-related enzymes that has gained considerable interest is CYP4Z1. This enzyme has been expressed in many tumours and has been hypothesized as a potential biomarker or target for novel anticancer therapies. PATIENTS AND METHODS: CYP4Z1 overexpression was immunohistochemically examined in a large panel of colon tissue types including normal, benign, primary and metastatic ones, and the enzyme's relation to histopathological features and patient survival was evaluated. RESULTS: A high CYP4Z1 expression was observed in benign, primary and metastatic colon tissues compared to a weak or lack of expression in normal tissues. Importantly, there was a significant differential in CYP4Z1 expression where it was stronger in metastatic, primary and benign, respectively (p < 0.05). A significantly high rate of CYP4Z1 expression was found in high histological grades and late stages of the disease, where its expression was more evident in patients with metastasis in the lymph nodes (p < 0.05). Interestingly, CYP4Z1 expression was identified an independent prognostic predictor of poor overall survival of colon cancer patients (p = 0.003). CONCLUSION: CYP4Z1 was distinctly overexpressed in benign, primary and metastatic colon tissues compared to corresponding normal tissues. This differential in CYP4Z1 expression across different types of colon tissues strongly supports CYP4Z1 as potential biomarker and target for novel anticancer therapy development.

Cytochrome 4Z1 Expression is Associated with Unfavorable Survival in Triple-Negative Breast Cancers.

PURPOSE: Triple-negative breast cancer (TNBC) is characterized by high mortality rate, and its clinical management is difficult and complex. Therefore, there is a need for extensive efforts aimed at accelerating the discovery of novel therapies for TNBC. CYP4Z1 has been implicated in the development of breast cancer. The current study aimed at characterizing the expression of CYP4Z1 on TNBC. MATERIALS AND METHODS: Using immunohistochemistry, CYP4Z1 expression was evaluated on 122 TNBC samples, four samples of breast cancers expressing ER, PR, and HER-2, and four samples of normal breast tissues. The association between the enzyme and various histopathological features and survival of patients were determined. RESULTS: CYP4Z1 was strongly expressed in 83.3% of various histopathological subtypes of TNBC, when compared to negative expression in normal breast tissues. Interestingly, there were marked variations in CYP4Z1 expression with respect to histopathology subtype, histological grade, histological stage and tumor diameter. There was a high incidence of CYP4Z1 expression in patients with advanced grades, late stages and larger tumor sizes. Importantly, CYP4Z1 expression was correlated with the survival of TNBC patients, but it was an independent determinant of the poor prognosis of TNBC (p< 0.05). CONCLUSION: CYP4ZI may be a potential biomarker or target for evolving new CYP4Z1-targeted treatments.

Profiling of CYP4Z1 and CYP1B1 expression in bladder cancers.

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes' relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. CYP4Z1expression was significantly associated with tumour grade and stage where the expression was markedly increased in a high grade and advanced stage of the disease (p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging (p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.

Frequency of mismatch repair protein deficiency and PD-L1 in high-grade gliomas in adolescents and young adults (AYA).

Central nervous system tumors in adolescents and young adults (AYA) are rarely reported in the literature. The association with cancer predisposition syndrome is not established. Programmed death ligand 1 (PD-L1) can predict the potential response of patients to immunotherapy. A link between mismatch repair protein deficiency (MMRP-D) and response to immunotherapy is established. P53 is reported to be positive in MMRD-D cases. We aim to investigate the frequency of MMRP-D in AYA with high-grade glioma and any potential association with PD-L1. A total of 96 cases were tested including 49 (51.0%) cases of glioblastoma. Six cases (6.25%) were MMRP-D, 17 (17.7%) were PD-L1 positive, mostly in grade IV tumors (8.7% in grade III compared to 26% in grade IV, p value = 0.027), and 69 (71.9%) were P3 positive. None of the MMRP-D cases expressed PD-L1. P53-positive cases were mostly MMRP proficient (n = 67; 74.4%, p value 0.051). Fourteen cases (28.7%) were positive for both PD-L1 and P53, while p53-positive grade IV tumors were mostly associated with negative PD-L1 (n = 29, 58%, p value = 0.043). MMRP deficiency does not appear to be prevalent in high-grade glioma in AYA. Expression of PD-L1 in a quarter of cases might suggest a role for immunotherapy in high-grade glioma.

Central Nervous System Tumors in Adolescents and Young Adults: An Epidemiological Study from Jordan.

BACKGROUND: The adolescent and young adult (AYA) age group lacks targeted epidemiologic studies that assess the prevalence and outcome of tumors. We aim to provide deep analysis of the epidemiology of central nervous system (CNS) tumors in AYA in Jordan. METHODOLOGY: This is a retrospective study for all CNS tumors in the AYA group patients diagnosed and managed at King Hussein Cancer Center in 2007-2016. A patient list was retrieved from the Center's Cancer Registry, and clinicopathologic data were reviewed individually from the patients' records. RESULTS: A total of 370 cases of primary CNS tumors were retrieved, with a median age of 28.5 years. Males outnumbered females; 57.6 and 42.4%, respectively. Most tumors occurred in the cerebrum (62.2%, n = 230), the frontal lobe was the most commonly affected (29%). Glioma was the most common histologic category (58.9%, n = 218), with high-grade tumors, including glioblastoma and anaplastic astrocytoma, prevailing. Embryonal tumors comprised the second most common group (16.8%, n = 62). Medulloblastoma was the prototype of embryonal tumors (91.9%; n = 57). Glioma tended to affect the older age group than embryonal tumors (p value = 0.002). On last available follow-up, 29.5% were lost to follow-up, 36% were alive, and 34.6% were deceased. The median overall survival (OS) for all tumors was 47.6 months. Embryonal tumors had a better outcome than glioma (median OS 76.3 vs. 30.3 months, respectively; p value = 0.001). CONCLUSIONS: High-grade glioma affecting the cerebrum was the most common tumor among AYA age group and was associated with a less favorable outcome compared to embryonal tumors. More research is needed to address this special age group.

Bifocal Tibial Kaposiform Hemangioendothelioma Responsive to Vincristine Therapy: A Case Report.

BACKGROUND Kaposiform hemangioendothelioma is a rare locally aggressive vascular endothelial-derived spindle cells neoplasm. Herein, we report a rare case of bifocal tibial kaposiform hemangioendothelioma. CASE REPORT A 9-year-old female presented with a 2-year history of pain and swelling in the left leg. The patient had a high plasma level of the D-dimer and fibrinogen. Radiography revealed a centric lytic lesion on the left proximal tibial metaphysis and an eccentric lateral distal tibial metaphyseal. Histopathologic examination of the sample taken from the distal tibia revealed a dense spindle cell tumor with lobular architecture composed of compact spindle cells compressing small slit-like vascular spaces, forming glomeruloid nests. No necrosis was identified. Based on these findings and the positive immunohistochemical staining for CD31, CD34, and D2-40, the patient was diagnosed with kaposiform hemangioendothelioma. Treatment was started by using vincristine chemotherapy, after which the patient developed temporary peroneal neuropathy, which improved over the next 3 months. CONCLUSIONS Bifocal tibial kaposiform hemangioendothelioma lesions are unique in pediatric patients and can be successfully treated with vincristine chemotherapy. In these cases, the treating physician should be aware of peroneal neuropathy as a potential complication of vincristine administration.

Capillary Hemangioma as an Unusual Cause of Doughnut Sign on Bone Scan.

ABSTRACTS: A 28-year-old woman presented with a mass in her right leg, which, on plain radiograph, appeared as a lytic lesion in the mid-shaft of the tibia with cortical thinning but without periosteal reaction. Tc-MDP 3-phase bone scan demonstrated intense uptake in the periphery of the mass with a photopenic center, the so-called doughnut sign. Histopathology revealed a capillary hemangioma. This case demonstrates that the doughnut sign on bone scan can be caused by capillary hemangioma in addition to other reported bone pathologies, including aneurysmal bone cyst, giant cell tumor, and telangiectatic osteosarcoma.

The rising trend in papillary thyroid carcinoma. True increase or over diagnosis?

OBJECTIVES: To assess the changes in parameters of thyroid carcinoma, particularly papillary type, in the era of widespread use of sensitive diagnostic methods. We aim to investigate whether the increased frequency of thyroid cancer is true or resulted from over diagnosis. Methods: We conducted a retrospective study of 313 cases of thyroid carcinoma diagnosed at Jordan University Hospital and King Hussein Cancer Center from 2007-2015. Papillary carcinoma accounted for 290 (92.7%) of all cases. Cases were sub classified according to demographic features, histological type, size, stage, and other variables. For comparison of data, cases were subdivided into 2 study periods: Group I included patients diagnosed in the period 2007-2010, and Group II in the period 2011-2015. Results: The frequency of thyroid carcinoma has increased across the study period. Papillary carcinoma was the major type accounting for this increase. Papillary micro carcinomas ≤1cm accounted for 34.8% of cases of PTC. Most cases (52.4%) of papillary thyroid carcinoma (PTC) were localized stage tumors. Group II of the study witnessed a more than doubled number of cases of PTC compared to group I, with increased frequency of tumors of all sizes as well as tumors of both localized and regional stages. Conclusions: Our observed trend cannot be totally explained by over diagnosis and increased diagnostic scrutiny. This increase could be of true nature and cannot be explained by single cause.

Lymphoma presenting as a toothache: a wolf in sheep's clothing.

Although rare in the oral cavity, oral non-Hodgkin lymphoma frequently mimics odontogenic and other oral pathologies. The purpose of this report is to discuss the diagnostic difficulty in a case of a 75-year-old man with diffuse large B-cell lymphoma presenting initially as a toothache.