The Complex Connection between Obesity and Cancer: Signaling Pathways and Therapeutic Implications.

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/ß-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice.

Ovarian collision tumour consisting of a fibroma and a serous cystadenoma: A case report.

This article reports a case of an ovarian collision tumour consisting of an ovarian fibroma and a serous cystadenoma. A 60-year-old woman exhibited symptoms of post-menopausal bleeding and abdominal pain persisting for three months. Computerized tomography identified a solid mass with a cystic component in the right adnexa, and the patient underwent staging laparotomy. Gross examination of the right ovary revealed a cystic tumour with adjacent solid mass. The histopathological analysis identified a cystic mass that matched the characteristics of a serous cystadenoma, with an adjacent solid mass that matched the characteristics of a sex-cord stromal tumour, both located in the right ovary. Additionally, a small cyst that matched the characteristics of a serous cystadenoma was found in the left ovary. There have been only seven previously reported examples of this specific mix of ovarian tumours. Mostly affecting patients above 60 years of age, although tumour markers levels are normal, such cases may present with a complex clinical scenario, as in this case, and demand a comprehensive diagnostic and therapeutic approach.

The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia.

Chronic Myeloid Leukemia (CML) is characterized by chromosomal aberrations involving the fusion of the BCR and ABL genes on chromosome 22, resulting from a reciprocal translocation between chromosomes 9 and 22. This fusion gives rise to the oncogenic BCR-ABL, an aberrant tyrosine kinase identified as Abl protein. The Abl protein intricately regulates the cell cycle by phosphorylating protein tyrosine residues through diverse signaling pathways. In CML, the BCR-ABL fusion protein disrupts the first exon of Abl, leading to sustained activation of tyrosine kinase and resistance to deactivation mechanisms. Pharmacological interventions, such as imatinib, effectively target BCR-ABL's tyrosine kinase activity by binding near the active site, disrupting ATP binding, and inhibiting downstream protein phosphorylation. Nevertheless, the emergence of resistance, often attributed to cap structure mutations, poses a challenge to imatinib efficacy. Current research endeavours are directed towards overcoming resistance and investigating innovative therapeutic strategies. This article offers a comprehensive analysis of the structural attributes of BCR-ABL, emphasizing its pivotal role as a biomarker and therapeutic target in CML. It underscores the imperative for ongoing research to refine treatment modalities and enhance overall outcomes in managing CML.

Dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer.

INTRODUCTION: The resistance to chemotherapy is a significant hurdle in breast cancer treatment, prompting the exploration of innovative strategies. This review discusses the potential of dual-loaded liposomal carriers to combat chemoresistance and improve outcomes for breast cancer patients. AREAS COVERED: This review discusses breast cancer chemotherapy resistance and dual-loaded liposomal carriers. Drug efflux pumps, DNA repair pathways, and signaling alterations are discussed as chemoresistance mechanisms. Liposomes can encapsulate several medicines and cargo kinds, according to the review. It examines how these carriers improve medication delivery, cancer cell targeting, and tumor microenvironment regulation. Also examined are dual-loaded liposomal carrier improvement challenges and techniques. EXPERT OPINION: The use of dual-loaded liposomal carriers represents a promising and innovative strategy in the battle against chemotherapy resistance in breast cancer. This article has explored the various mechanisms of chemoresistance in breast cancer, emphasizing the potential of dual-loaded liposomal carriers to overcome these challenges. These carriers offer versatility, enabling the encapsulation and precise targeting of multiple drugs with different modes of action, a crucial advantage when dealing with the complexity of breast cancer treatment.

PTEN, ERG, SPINK1, and TFF3 Status and Relationship in a Prostate Cancer Cohort from Jordanian Arab Population.

Background and Objectives: Prognostic biomarkers in prostate cancer (PCa) include PTEN, ERG, SPINK1, and TFF3. Their relationships and patterns of expression in PCa in developing countries, including Jordan, have not yet been investigated. Materials and Methods: A tissue microarray (TMA) of PCa patients was taken from paraffin-embedded tissue blocks for 130 patients. PTEN, ERG, SPINK1, and TFF3 expression profiles were examined using immunohistochemistry (IHC) and correlated with each other and other clinicopathological factors. Results: PTEN loss of any degree was observed in 42.9% of PCa cases. ERG and TFF3 were expressed in 59.3% and 46.5% of PCa cases, respectively. SPINK1 expression was observed in 6 out of 104 PCa cases (5.4%). Among all PCa cases (n = 104), 3.8% (n = 4) showed SPINK1+/ERG+ phenotype, 1.9% (n = 2) showed SPINK1+/ERG- phenotype, 56.7% (n = 59) showed SPINK1-/ERG+ phenotype, and 37.5% showed SPINK1-/ERG- phenotype (n = 39). Among ERG positive cases (n = 63), 6.3% were SPINK1 positive. Among SPINK1 positive cases (n = 6), 66.7% were ERG positive. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3 (6/6). Additionally, a statistically significant loss of PTEN expression was observed from Gleason Score 6 (GS6) (Grade Group 1 (GG1)) to GS9-10 (GG5); (p-value 0.019). Conclusions: This is the first study to look at the status of the PTEN, ERG, SPINK1, and TFF3 genes in a Jordanian Arab population. Loss of PTEN has been linked to more aggressive prostate cancer with high GSs/GGs. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3. Our results call for screening these biomarkers for grading and molecular subtyping of the disease.

Mature cystic teratoma of the ovary with malignant transformation of tall cell subtype of papillary thyroid carcinoma.

Malignancies rarely occur in somatic parts of mature cystic teratoma of the ovary. Squamous cell carcinoma is the most common form of cancer that can develop in mature cystic teratoma. Other less frequent malignancies include melanoma, sarcoma, carcinoid, and germ cell neoplasms. Only three cases have been reported as papillary thyroid carcinoma arising in struma ovarii. We present a unique case of a 31-year-old female patient who presented with a left ovarian cyst and underwent conservative surgical management in the form of cystectomy. Histopathological examination confirmed the diagnosis of a tall cell subtype of papillary thyroid carcinoma arising from a small focus of thyroid tissue in a mature cystic teratoma of the ovary. The patient was followed up for 60 months with an uneventful clinical course. For a better understanding of such rare cancers, collaborative retrospective studies on large databases with other medical centers are required.

Development and validation of Ran as a prognostic marker in stage I and stage II primary breast cancer.

PURPOSE: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes. PATIENTS AND METHODS: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS). CONCLUSION: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages.

Impact of exosome therapy on pancreatic cancer and its progression.

Pancreatic cancer, one of the most aggressive tumors, has a dismal prognosis because of the low rates of early identification, fast progression, difficulties following surgery, and the ineffectiveness of current oncologic therapies. There are no imaging techniques or biomarkers that can accurately identify, categorize, or predict the biological behavior of this tumor. Exosomes are extracellular vesicles that play a crucial rule in the progression, metastasis, and chemoresistance of pancreatic cancer. They have been verified to be potential biomarkers for pancreatic cancer management. Studying the role of exosomes in pancreatic cancer is substantial. Exosomes are secreted by most eukaryotic cells and participated in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long non-coding RNA, circular RNA, etc., play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, in this concise review, we intend to summarize exosomes components and isolation, exosome secretion, function, importance of exosomes in the progression of pancreatic cancer and exosomal miRNAs as possible pancreatic cancer biomarkers. Finally, the application potential of exosomes in the treatment of pancreatic cancer, which provides theoretical supports for using exosomes to serve precise tumor treatment in the clinic, will be discussed.

A Genetic and Immunohistochemical Analysis of Helicobacter pylori Phenotypes and p27 Expression in Adenocarcinoma Patients in Jordan.

Stomach (gastric) cancer is one of the most prevalent and deadly cancers worldwide and most gastric cancers are adenocarcinomas. Based on prior research, there is an association between Helicobacter pylori (H. pylori) infection together with the frequency of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue (MALT) lymphoma, and antral gastritis. Helicobacter pylori virulence and toxicity factors have been identified before that significantly influence the clinical outcomes of H. pylori infection and gastric adenocarcinoma. However, it remains unclear exactly how different strains of H. pylori affect gastric adenocarcinoma. Current research suggests this involves tumor suppressor genes, like p27 but also H. pylori toxic virulence proteins. Therefore, we quantified known H. pylori genotypes within adenocarcinoma patients to establish the prevalence of known toxins that include cytotoxin-associated gene A (cagA) as well as vacuolating cytotoxin A (vacA) within patients of variable adenocarcinoma diagnosis. This analysis used gastrectomy samples validated for DNA viability. The incidence of H. pylori in adenocarcinoma patients in Jordan was established to be 54.5% positive (ureA gene positive) with cagA genotype occurrence at 57.1%, but also in this population study vacA gene ratios found to be 24.7%:22.1%:14.3%:14.3%. (vacAs1:vacAs2:vacAm1:vacAm2). Using immunohistochemistry (IHC), we confirmed with statistical significance that p27 was dysregulated and suppressed, within nearly all H. pylori vacA genotypes. In addition, within 24.6% of H. pylori samples analyzed was a different bacterial genotype, and curiously that p27 protein expression was retained in 12% of tested adenocarcinoma H. pylori samples. This is suggestive that p27 could be used as a prognostic indicator but also that an unknown genotype could be contributing to the regulatory effects of p27 protein within this bacterial and cellular environment that may include other virulence factors and unknown immune system regulatory changes.

Impact of COVID-19 Exclusive Allocation Strategy on Quality of Healthcare: A Study From Jordan, 2020.

The COVID-19 pandemic has brought uncertainty to everyday medical practice. Deciding how to ration limited healthcare resources is difficult and requires the involvement of higher authorities in each country. In this article we focus on the Jordanian strategy of allocating tertiary healthcare centers exclusively for COVID-19 patients and postponing all other treatments and healthcare provision. We collected secondary data on admissions, occupancy of hospital beds, and length of stay at emergency departments and outpatient clinics, as well as surgeries conducted, between March and May 2020 at King Abdullah University Hospital in Irbid, Jordan. We also conducted a literature review to explore health resource utilization and allocation in terms of health service quality. Our findings showed a major decrease in the demand for health services at the hospital including admissions, emergency department visits, outpatient clinic visits, surgeries, and radiology during the study period. These findings indicate the enormous impact of the pandemic on the largest segment of patients in Jordan-those who depend on government health insurance-to manage their routine healthcare needs, which may affect the health status of patients. Authorities should address the COVID-19 pandemic holistically by prioritizing both COVID-19 cases and non-COVID-19 cases and should draft a framework for managing future pandemics. Moreover, planning a strategy to accommodate the number of people waiting for elective surgeries and routine healthcare should be in place to minimize the burden of this pandemic.

Soft Tissue Sarcomas: A 16-Year Experience of a Tertiary Referral Hospital in North Jordan.

Background and Objectives: Sarcomas are rare malignant tumors of mesenchymal origin. Their low prevalence and histological heterogeneity make their diagnosis a challenging task. To the best of our knowledge, the epidemiology of soft tissue sarcomas (STSs) was not well studied in Jordan. This study thus aimed to determine STS epidemiologic trends at King Abdullah University Hospital (KAUH); a tertiary hospital that provides cancer healthcare for 70% of the population in Irbid Governorate, North Jordan. The findings of this study will provide a good reference point of the burden of STSs in Jordan and the Middle East region. Materials and Methods: All cases with confirmed STS diagnoses who attended KAUH from January 2003 until December 2018 were included in the initial analysis. Bone sarcomas, gastrointestinal stromal tumors and uterine sarcomas were not included in the study. Information collected from the pathology reports and electronic medical records was used to determine STS prevalence, incidence rate, age and gender distributions, histological types and anatomic location. Cases were reviewed by three pathologists with interest in soft tissue tumors. The findings were compared with literature. Results: In total, 157 STS cases were reported (1.9% of cancers diagnosed at KAUH during the 16-year study period). Crude annual incidence rate (IR) per 100,000 person-years ranged from 0.48 in 2015 to 1.83 in 2011 (average = 1.04). Age-standardized IR (ASR)(World WHO 2000-2025) was 1.37. Male:female ratio was 1.3:1. Median age was 39 years. Age ranged from <1 year to 90 years. Overall STS rates increased with age. The most common histological types were liposarcoma (19%), rhabdomyosarcoma (17%) and leiomyosarcoma (10%). The most common anatomic location was the extremity (40.1%), followed by the trunk (14.7%), then head and neck (10.8%). Conclusion: STSs are rare in North Jordan. A slight increase in their incidence was identified during the study period similar to global trends. The collection of relevant data on established risk factors along with a broader scale evaluation of the epidemiology of STS in the Middle East region is recommended to better evaluate disease burden and trends.

Compliance with safety measures and risk of COVID-19 transmission among healthcare workers.

AIM: This study aimed to determine the compliance of healthcare workers (HCWs) with the hospital safety measures and the prevalence of hospital-acquired COVID-19 infection among them. METHODOLOGY: HCWs at King Abdullah University Hospital (KAUH) assigned for COVID-19 patients between 18 March and 10 June 2020 were tested for past infection using total anti-SARS-CoV-2 immunoglobulin assay, demographic data and compliance with safety measures were assessed using a questionnaire. RESULTS: A total of 340 HCWs participated in the study, 260 were close direct care. Three HCWs tested positive for total anti-SARS-CoV-2 immunoglobulin. Close direct care were more compliant with personal protective guidelines than those providing direct care. CONCLUSION: HCWs compliance with personal protective guidelines might explain the low prevalence of COVID-19 infection in hospital settings.

Primary Clear Cell Sarcoma of the Lung: a Case Report.

BACKGROUND: Clear Cell Sarcoma of Soft Tissue (CCSST), or melanoma of the soft part, is a rare, aggressive tumor that originates in the aponeurosis and fasciae of the distal parts of the extremities. Reports from other sites of the body are rare. OBJECTIVE: We are reporting an extremely rare tumor that presented as a central left-sided lung mass and found to be clear cell sarcoma of soft tissue. METHODS: We report a 24-year-old male patient presented with recurrent attacks of left-sided chest pain associated with cough and dyspnea. RESULTS: Imaging showed a central left-sided 8*5.5*5 cm lung mass. The age of the patient and the radiological characteristics of the lesion were suggestive of a benign pathology. After histopathological assessment of the lesion, suspicion of the malignant process was raised, mainly melanoma of soft part and PEComa. The patient underwent left-sided pneumonectomy. The postoperative histological examination, immunohistochemical findings including positive staining for S-100, HMB-45, and Melan-A, and positive FISH study for EWSR1 gene rearrangements supported the diagnosis of CCSST originating primarily in the major fissure of left the lung. CONCLUSION: The rarity of CCSST in general and tumors originating in the lung primarily raise the challenges in hypothesizing a differential diagnosis, choosing proper investigations and treatment methods. The histological examination, immunohistochemical, and cytogenetics of the tumor are mandatory to reach the final diagnosis.

Cellular pathology practice in the era of COVID-19 pandemic-related lockdowns - Experience from a tertiary hospital: A retrospective observational study.

BACKGROUND: The COVID-19 pandemic had many implications on healthcare services, including cellular pathology. The pandemic-related lockdown was applied in Jordan from March to May 2020. King Abdullah University Hospital (KAUH) was chosen to provide care for COVID-19 patients during that period. Since there was no experience in dealing with COVID-19 patients, the hospital maintained some essential services but canceled elective surgeries and procedures. The rationale was to prioritize care for COVID-19 patients and to provide better adherence to infection control policies and protect non-infected patients and healthcare workers. The purpose of the present study is to investigate the impact of COVID-19 pandemic restrictions on cellular pathology practice patterns at KAUH. METHODS: This is a retrospective observational study conducted at KAUH. All cellular pathology reports during the 2020 national lockdown were retrieved. The total numbers of specimens including types and procedures were recorded. Data were compared with the corresponding data in 2019 when there was no pandemic and when hospital and laboratory services were run in full capacity. RESULTS: 2020 lockdown period showed a 57.9% reduction in the total number of specimens received at the cellular pathology laboratory as compared to the corresponding period of 2019 (1400 versus 3322). Emergency procedures have represented 99.1% of the service during the lockdown with a remarkable diversity shift. CONCLUSION: There was a significant drop in the number of specimens dealt with at KAUH cellular pathology laboratory during the COVID-19 pandemic-related national lockdown. We learned from this pandemic how to adapt to such circumstances by adjusting our way of working to reach the best level of staff safety while maintaining highly productive work. Implementing digital pathology platforms, working from home strategies and alternative training methodologies have emerged as an essential need.

Human Mammary Tumor Virus, Human Papilloma Virus, and Epstein-Barr Virus Infection Are Associated With Sporadic Breast Cancer Metastasis.

BACKGROUND: Viral cause of sporadic breast cancer (SBC) has been suggested based on the experimental murine model of mammary tumor caused by mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV), and human papillomavirus (HPV). While some studies have demonstrated the presence of viral sequences of MMTV, HPV, and EBV in breast cancer cells, others failed. These contradictions may be attributed to the geographical distribution of breast cancer incidence and/or technical variations. In the current study, we aimed to investigate the correlation of MMTV, HPV, and EBV infections with the development of breast cancer in Jordanian patients. METHODS: One hundred SBC tissue samples were subjected to laser capture microdissection for the selection of tumor cells populations. Fluorescence polymerase chain reaction (PCR) was used to detect the presence of the MMTV env-like sequences. Real-time PCR was used for HPV and EBV detection, and EBV was further confirmed by chromogen in situ hybridization (CISH). RESULTS: Mouse mammary tumor virus, HPV, and EBV were detected in SBC in 11%, 21%, and 23%, respectively. Only 3 of 52 (5.7%) positive cases demonstrated multiple virus infections. However, 49 of 52 (94%) of the positive cases revealed the presence of 1 type of viral sequences. Consequently, 52% of the studied breast cancer cases were infected with at least 1 type of the aforementioned viruses. CONCLUSIONS: The current cohort suggests that MMTV, HPV, and EBV have a potential role in the development of breast cancer and adding more reasons to proceed with the quest of a possible viral origin of breast cancer.

A 47-Year-Old Woman with Immunoglobulin G4 (IgG4)-Related Disease Involving the Right Ovary.

BACKGROUND Immunoglobulin G4 (IgG4)-related disease is immune-mediated and was first proposed as a defined entity after studies on patients with autoimmune pancreatitis. Since then, it has been reported in many organs. Involvement of the ovaries is rare, and to our knowledge, only 2 cases have been reported in the literature. IgG4-related disease is associated with increased serum IgG4 levels. Organ involvement includes a lymphoplasmacytic infiltrate, fibrosis, and obliterative phlebitis, with immunohistochemistry showing IgG4-positive plasma cells. This report is of a case of IgG4-related disease involving the right ovary. CASE REPORT A 47-year-old woman presented with a right ovarian cyst. An ultrasound scan revealed a complex right ovarian cyst with multiple septations. The hormonal profile and tumor markers were unremarkable. Gross examination showed fragments of cyst wall. Histologic examination revealed a follicular cyst, surrounded by a dense lymphoplasmacytic infiltrate rich in eosinophils, partially obliterative phlebitis, and fibrosis. Immunohistochemically, IgG marked most of the plasma cells, of which 70% expressed IgG4, with a count >50 cells per high-power field. Subsequent testing of serum IgG4 showed that the level was elevated (330 mg/dL). A diagnosis of IgG4-related disease was made. CONCLUSIONS Ovarian involvement by IgG4-related disease is rarely described in the literature. Our patient is likely to be the third case. We believe that cumulative findings from our case along with the 2 already reported cases increase awareness and may establish a framework for building more objective criteria to define this entity in the ovaries, similar to what has been achieved in some other organs.

Impact of Obesity on Clinicopathologic Characteristics and Disease Prognosis in Pre- and Postmenopausal Breast Cancer Patients: A Retrospective Institutional Study.

Purpose: To investigate the association between obesity and breast cancer clinicopathologic characteristics at presentation along with prognostic impact among Jordanian breast cancer patients. Such data are lacking in Arabian countries. Methods: In this retrospective study, 348 breast cancer patients were included. Analyses were conducted for associations between body mass index (BMI) and age at diagnosis, tumor clinicopathologic characteristics, and molecular subtypes. Eight prognostic factors were considered, and total prognostic scores were calculated. The analysis was stratified by menopausal status. Multivariate logistic stepwise regression analysis was conducted to identify predictors for breast cancer recurrence and death. Results: Mean age at diagnosis was 50.98 ± 10.96 years. Mean BMI at diagnosis was 29.52 ± 5.32 kg/m2. Mean age at diagnosis was significantly higher for overweight and obese patients compared to underweight/normal patients (P < 0.001). A significant positive correlation was observed between patient age and BMI at diagnosis (r = 0.251, P < 0.001). Grade of carcinoma was significantly correlated with BMI in the whole population examined (P=0.003). Obese breast cancer patients had significantly higher prognostic scores compared to nonobese cases, indicating worse prognostic features at presentation (P=0.034). Stratification of data analysis based on menopausal status revealed significant associations between obesity and each of tumor stage and grade among postmenopausal but not premenopausal patients (P=0.019 and P=0.031, respectively). Similarly, postmenopausal obese patients had significantly higher prognostic scores compared to nonobese counterparts (P=0.007), indicating worse prognosis, a finding which was also absent among premenopausal breast cancer patients. No significant association between BMI with expression status of hormone receptors, HER2, lymphovascular invasion, and molecular subtypes was found among patients. BMI was a significant predictor for disease recurrence in which obese breast cancer patients had greater odds (2-fold) to develop locoregional and distant recurrence compared to nonobese cases (P=0.011). Conclusions: Obesity was associated with advanced stage and grade of breast carcinoma at diagnosis. The impact of BMI on clinicopathologic characteristics and prognosis was confined to postmenopausal cases. Jordanian obese breast cancer patients are at greater risk of breast cancer recurrence and reduced survival compared to their nonobese counterparts.

Prevalence of EGFR and ALK Mutations in Lung Adenocarcinomas in the Levant Area - a Prospective Analysis

Background: A significant percentage of lung adenocarcinomas have a driver mutation. To date, there has been no assessment of the prevalence of such mutations in a Middle Eastern population. The present multicenter prospective study of formalin fixed paraffin embedded (FFPE) tissues from patients diagnosed with lung adenocarcinoma was performed to assess the prevalence of EGFR and ALK mutations in the Levant. Methods: Patients of Middle Eastern origin with lung adenocarcinomas at 10 sites in Lebanon, Jordan and Iraq were prospectively enrolled. Tumors were tested for EGFR by PCR and for EML4-ALK translocation by fluorescence in situ hybridization (FISH). Results: A total of 210 patients were enrolled, 139 (66.2%) males and 71 females (33.8%), with a mean age of 63.4 years. EGFR testing of 205 (97.6%) demonstrated the wild type in 173 (84.4%) and mutated forms in 32 (15.6%). Some 46.9% of EGFR positive patients were non-smokers and 62.5% were females as opposed to 22.4% and 33.8%, respectively, in the general population. As for the EML4-ALK translocation, testing in 157 (74.8%) cases gave negative results in 154 (98.1%) , only 3 being positive (1.9%), 2 being females and 2 non-smokers.Conclusion: Our study established a 15.6% EGFR mutation rate in lung adenocarcinomas with ALK translocation mutations in only 1.9%, as compared to a 15-20% and 5%, respectively, in the Western literature.