Middle East Journal of Cancer
Volume:11 Issue: 3, Jul 2020

Lung cancer is one of the most frequently diagnosed malignant neoplasms in the world. The pulmonary carcinomas are divided into two major categories, namely small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC).Traditionally, the treatment for NSCLC was based on tumor stage, irrespective of histologic subtypes; over the recent years, however, with the development of targeted therapies with different adverse or therapeutic effects on each subtype, it is crucial to correctly subcategorize NSCLC. Utilizing Immunohistochemical (IHC) markers may be conducive to obtain this objective, yet no single marker is sensitive or specific enough to differentiate SCC and adenocarcinoma. Therefore, in the present research, we want to use a panel consisting of P63, CK 5/6, TTF-1, and Napsin A.

83 cases of NSCLC (36 adenocarcinoma, 37 squamous cell carcinoma and 10 poorly differentiated carcinoma) were selected. IHC examination for P63, TTF-1, Napsin A, and CK 5/6 were performed on tissue sections obtained from formalin-fixed, paraffin embedded blocks.

TTF1 had 94% sensitivity and 69% specificity with PPV 73% and NPV 92%, and NaspsinA had 91% sensitivity and 97% specificity with PPV 97% and NPV 92% as regards the diagnosis of adenocarcinoma. P63 had 100% sensitivity and 84% specificity with PPV 87% and NPV 100%, and CK5/6 had 100% sensitivity and 69% specificity with PPV 78% and NPV 100% in the diagnosis of squamous cell carcinoma.

Using an IHC panel of TTF-1, Napsin A, P63, and CK5/6 it is possible to reliably diagnose poorly differentiated NSCLC with no evident glandular or squamous differentiation.

The main oncogenic action of CD99 and cyclin D1 biomarkers is referred to any mutation, amplification, and overexpression in cyclin D1 coding gene, altering cell cycle progression as the main mechanism observed in a variety of tumors. A few studies attempted to detect the overexpression of cyclin D1 and CD99 and in certain types of tumors such as Ewing's sarcoma and rhabdomyosarcoma. The present study aimed to assess the prevalence of CD99 and cyclin D1 overexpression in these two types of tumors. We also described this overexpression according to the patients and tumor indicators.
This cross-sectional survey was performed on 30 consecutive patients with Ewing's sarcoma and 22 patients with rhabdomyosarcoma and hospitalized in Shafa hospital in Tehran between 2009 and 2014. The assessment of CD99 and cyclin D1 markers was based on immunohistochemical assessment using the formalin fixed and paraffin embedded tissue samples of the two tumors.
Almost all Ewing's sarcomas had membranous patterns of CD99 while this marker was negative in most patients with rhabdomyosarcoma. Therefore, detecting membranous CD99 could specifically detect Ewing's sarcoma and distinguish it from rhabdomyosarcoma. Moreover, contrary to rhabdomyosarcoma which is accompanied with lower cyclin D1 intensity, all Ewing's sarcomas were characterized by moderate to severe cyclin D1 intensity. Similarly, almost all those with Ewing's sarcoma had diffuse cyclin D1 extension; whereas, the pattern of cyclin D1 extension in rhabdomyosarcoma was mostly negative or focal.
The detection of CD99 and cyclin D1 overexpression and their intensity and extension patterns can specifically distinguish Ewing's sarcoma from rhabdomyosarcoma.

Genomic polymorphisms of DNA repair enzymes/excision repair cross complementation group 1 (ERCC1), excision repair cross complementation group 2 (ERCC2), and X-ray repair cross complementation group 1 (XRCC1) correlate with survival and therapeutic responses in colorectal cancer (CRC) patients. Therefore, the present study examined the frequency of ERCC1 C118T, ERCC2 Lys751Gln, and XRCC1 Arg399Gln polymorphisms and their prognostic and predictive values in CRC patients. In this retrospective study, a total of 143 CRC patients were evaluated for these polymorphisms by PCR-RFLP. The majority of the patients showed heterozygous C/T (56%) compared to wild type C/C (29%) and variant T/T (15%) genotypes for ERCC1 C118T polymorphism. ERCC2 Lys751Gln polymorphism showed wild type A/A (44%), heterozygous A/C (40%), and variant C/C genotypes (16%). The frequency of XRCC1 Arg399Gln polymorphism was 48% (wild type G/G), 42% (heterozygous G/A), and 10% (variant A/A). The relapse-free survival (RFS) significantly decreased in patients with ERCC1 118 C/C wild type genotype in the subgroups of patients with advanced stage and colon cancer; however, variant T/T genotype correlated with reduced overall survival (OS) in patients treated with combined drug 5-FU/Oxaliplatin. Taken together, in CRC patients and patients treated with 5-FU/Oxaliplatin, ERCC2 Lys751Gln A/A wild type genotype led to significantly unfavorable clinical outcomes. However, XRCC1 Arg399Gln polymorphism did not show any significant association with prognosis. Additionally, on analyzing combined effect of ERCC1 and ERCC2 polymorphisms, a significant reduced OS in patients with both unfavorable genotypes (ERCC1: C/C and ERCC2: A/A) was found. Furthermore, in the subgroup of patients treated with 5-FU/Oxaliplatin, RFS and OS significantly decreased in patients with both unfavorable genotypes (ERCC1: T/T and ERCC2: A/A). The significant relationship of ERCC1 C118T and ERCC2 Lys751Gln polymorphisms with prognosis and treatment response reflects the vital role of these molecules as prognostic and predictive markers in patients with CRC. Additionally, the combined evaluation of ERCC1 and ERCC2 polymorphisms might identify high risk CRC patients with poor prognosis.

Our purpose was to investigate the effect of berberine (BER) and doxorubicin (DOX) on the expression of stem cell markers Nanog and microRNA- 21 in MCF-7 cells.
The study was an in vitro study employing the human breast cancer cell line MCF-7 that was divided into four groups: Group I: MCF-7 cell line maintained in drug-free environment as untreated control, Group II: MCF-7 cell line treated with different concentrations of DOX, Group III: MCF-7 cell line treated with various concentrations of BER. Group IV: MCF-7 cell line treated with different concentrations of combined DOX and BER. MTT assay determined the metabolic activity and viability of MCF-7 cells for all groups. We further extracted total RNA from MCF-7 cells, and RT-PCR assayed the expression of Nanog and miRNA-21.
The results revealed that DOX and/or BER decreased the percentage of viable MCF-7 monolayer and mammospheres breast cancer cells in a concentrationdependent manner. Moreover, the combination of DOX and BER generated synergistic anticancer effect on MCF-7 monolayer cells and mammospheres. In addition, DOX alone, BER alone, and their combination significantly reduced Nanog and miRNA- 21 gene expression in MCF-7 mammospheres compared with untreated mammospheres.
BER may affect the viability of breast cancer cells through downregulation of Nanog and miRNA-21 gene expression, ultimately enhancing the sensitivity of breast cancer cell line to DOX. BER may be an effective chemotherapeutic agent against breast cancer where the combination of DOX and BER generates synergistic anticancer effects.

Radiotherapy induces tumor cell death through DNA damage. Direct relationship between radiation therapy and the immune system is responsible for many of the antitumor effects of radiotherapy. The effects of radiation therapy extend beyond direct cytotoxicity on tumor cells to additional systemic antitumor effects. The objective of this study was to evaluate the effect of radiotherapy on the circulating levels of tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), CD8+ cytotoxic T lymphocytes and CD56+ natural killer cells in breast cancer patients. This study included 90 women divided into two main groups: Group I: 45 patients with stage II-III invasive breast carcinoma, group II: 45 healthy women as a control group. All studied patients received adjuvant radiotherapy after surgery. Enzyme-linked immunosorbent assay provided the measurement of TNF-α and INF-γ. Flow cytometry assessed the levels of CD8+ cytotoxic T lymphocytes and CD56+ natural killer cells. A significant reduction occurred in the percent of CD8+ and CD56+ cells in breast cancer patients after radiotherapy. There was a significant increase in both TNF-α and INF-γ in the plasma of breast cancer patients after radiotherapy. TNF-α and INF-γ cytokines significantly increased while the percent of CD56+ and CD8+ cells significantly decreased following exposure to radiotherapy. Such immune modulatory potential and increase in the knowledge of radiation induced out of field and systemic effects, foresee a rapid progress in the development and clinical application of new combined radiotherapeutic and immunotherapeutic approaches.

Few studies have investigated pancreatic cancer in Tunisia and there are no reported survival data. The aim of this study was to analyze the epidemiologic profile, treatment modalities, and survival and prognostic factors of patients with pancreatic cancer in Tunisia.
In this retrospective study, we included patients treated between 2001 and 2016 for a histologically proven pancreatic cancer in the Department of Medical Oncology in Tunisia.
We examined 130 patients with a median age of 58.7 years and a sex ratio of 1.8. Thirty percent had surgery for a localized disease. Among resected patients, 14% received adjuvant chemotherapy. 14.5% of the patients with borderline resectable tumors underwent induction chemotherapy without leading to surgery. Palliative chemotherapy was administrated for unresectable locally advanced (14%) and metastatic (41.5%) tumors. Median overall survival for localized, locally advanced, and metastatic disease was 20.5, 10.4, and 6.3 months, respectively. Independent prognostic factors were female gender, performance status, tumor localization, and chemotherapy.
Unlike what was published in the literature, patients in our study were younger and there was a male predominance. Survival rates were low even for localized stages. Treatment strategy, chemotherapy protocols, survival, and prognostic factors were in line with the literature.

Bronchus and lung cancer (BLC) is the first most prevalent cancer in terms of incidence and mortality worldwide. It is estimated that the number of new BLC cases will rise up to 15 million per year by 2020. We conducted this study using the data obtained from Fars Population Based Cancer Registry (FPBCR). The National Institute of Statistics (NIS) website provided the population data on Fars province. Additionally, we calculated the ASR through the WHO’s standard population 2000. The standardized rates were calculated via R software and the rate trends were analyzed using chi-square test. Over a 5-year period (2011-2015), 1466 new BLC cases were registered in Fars province, 1009 men (68.8%) and 437 women (31.2%). BLC was amongst the first 10 most prevalent cancers in both genders. The annual incidence rate of BLC was defined to be 7.69-10.78 per 100,000 among men and 3.00-4.52 per 100,000 among women. BLC is amongst the most prevalent cancers with geographical variations in incidence rates. Consistent with cancer reports from other province, relatively high rates of BLC were observed in Fars province, particularly among men.

Breast cancer is the most common cancer among women. The objective of this study was to determine the breast self-examination (BSE) and mammography compliance based on health belief model constructs among female healthcare workers in the city of Aq Qala. We conducted this cross-sectional study between November 2015 and February 2016 in Aq Qala city, northern Iran. In this regard, we selected 261 female healthcare workers through census. Data were gathered using Rakowski’s stages of change and Champion health belief model scale. We entered the collected data into SPSS 16 and analyzed them via descriptive statistical techniques along with Kruskal- Wallis, Mann-Whitney, chi-square, and Spearman rank correlation coefficient. The results showed that 26.4 % of the participants performed regular BSE and 19.3% underwent regular mammogram. Those with regular BSE had significantly more health motivation and self-efficacy (P≤0.05). Physicians had more susceptibility and self-efficacy for BSE and less BSE barriers (P≤0.05). There was a negative correlation between BSE confidence and barriers (r=-0.376). The results of binary logistic regression revealed that confidence was the only variable influencing BSE (OR=1.77, 95% CI=1.22, 2.572). Almost one-fourth of female healthcare workers of Aq Qala performed regular BSE. Moreover, one-fifth of women over 40 years of age underwent regular mammograms. Participants who performed regular BSE had higher health motivation, BSE self-efficacy, and lower perceived barriers. BSE adherence was more in physicians than in other groups. We recommend increasing confidence to surmount the barriers to perform BSE.

Cancer is a disease that not only affects the physical health, but also distresses the mental and emotional state of an individual. If beneficial coping strategies are not employed, the life quality of patients could be deteriorated. The present study seeks to examine various coping strategies adopted by cancer patients and design health promotion interventional strategies that will ameliorate the life quality of cancer patients.
Between February 2017 and March 2017, a descriptive cross-sectional study was conducted to assess the various coping strategies employed by cancer patients and its perceived effect on the quality of life. 90 cancer patients attending the cancer registry in Federal Teaching Hospital, Ido-Ekiti, within the study time frame were recruited. Data were analyzed and presented using descriptive statistics.
Various coping strategies as identified by respondents were attendance of social gathering (73.3%), engaging in physical activities (85.6%), spending time with family members (87.8%), participating in religious programs (88.9%), and solitude (50%). Overall, 88.9% and 87.8% respectively believed that attending religious programs and spending time with family members played a vital role in coping with cancer. However, only a few (37%) of these patients belonged to cancer support groups.
Few patients belong to cancer support groups, hence the recommendation that cancer patients be enlightened and encouraged to become members of cancer support groups.

The WHODAS-2 is a disability assessment tool built according to the conceptual framework of the international classification of functioning, disability, and health. This tool is a standard measure of disability dedicated to six specific domains. The aim of this study was to examine the psychometric properties of the World Health Organization Disability Assessment Scale 2.0 among Iranian cancer patients.
This study included cancer patients who referred to the Cancer Institute of Imam Khomeini Hospital, Tehran, Iran. For this purpose, we enrolled 320 patients and asked them to complete the questionnaires. Cronbach’s α assessed the internal consistency. Pearson’s correlation coefficient evaluated the divergent and convergent validity and correlation of WHODAS 2.0 with EORTC QLQ-C30, difficulty of emotion regulation, and co-rumination scales. Moreover, we assessed constructive validity by confirmatory factor analysis using smart PLS software.
The results showed that Cronbach’s α was 0.91 for the questionnaire and higher than 0.75 for all domains. Furthermore, there was a significant correlation among the WHODAS 2.0 with Cancer EORTC QLQ-C30 (r = 0.85), DERS (r = 0.78), and co-rumination scales (r = 0.71).
The version of the WHODAS 2.0 instrument had suitable psychometric properties in the sample of cancer patients. Therefore, it can be used in different populations and samples of cancer patients.

Balance impairment is related to breast cancer treatments, such as radiation therapy and chemotherapy. The aim of the present study was to investigate the effect of six-week resistance training with Thera-Band and combined training (training with Thera-Band and core stability training) on static and dynamic balance in breast cancer survivors.
In this randomized controlled trail, we divided 75 patients with breast cancer into three groups: 1) resistance training group (n=25, age= 46±5.82, BMI= 25.7±3.9), combined training group, (n=25, age= 48.9 ± 7.06, BMI=24.6 ± 3.5), and control group (n=25, age= 46±7.15, BMI= 25.17±3.7). Afterwards, we employed Single leg standing and Balance Error Scoring System (BESS) to measure the static balance; Four Square Step Test (FSST) and Timed Up and Go (TUG) were further used for dynamic balance in pre- and post-test. Exercise program was performed by two training groups for six weeks and three sessions per week. Resistance training with Thera-Band group performed 13 resistance trainings with Thera-Band. In combined group, resistance training was similar to Thera-Band group, but combined group were performed seven core stability trainings. We analyzed the data by two-way repeated measurements ANOVA using the software package SPSS V.22.
Results showed that there were no significant interaction effects indicating an exercise specific development, depending on the type of exercise or control condition (P>0.05). Furthermore, there were no significant deference among the resistance training with Thera-Band, the combined exercise, and the control groups (P>0.05).
It can be concluded that the six-week resistance training with Thera- Band and combined training (training with Thera-Band and core stability training) has no positive effects on static and dynamic balance in breast cancer survivors. We recommend that more studies be conducted in this regard.

We designed this study to assess the significant prognostic factors of both recurrence and death in patients with acute lymphoblastic leukemia in a university-based hospital using a parametric competing risks model.

In this retrospective study, we included 417 patients with acute lymphoblastic leukemia. Staining of bone marrow smears with Giemsa method confirmed the diagnosis, justifying at least 25% lymphoblast. Treatment of patients was based on the Berlin-Frankfurt-Münster (BFM) protocol. We considered the first recurrence of cancer as the event of interest and non-relapse mortality as a competing risk. The employed two-parameter Weibull model accounted for both the interest and the competing events.

The relapse-free survival and the five-year overall mortality rates of patients were 85.9% and 74%, respectively. The majority of the patients (72.7%) did not experience any event during the study period. We explained these events as first recurrence and non-relapse mortality, which occurred in 44 (10.6%) and 70 (16.8%) of the patients in the given order. The cumulative incident probability of the first recurrence and non-relapse mortality, were 13.43% and 18.61%, respectively.

Based on the model, we identified white blood cell count and central nervous system involvement as important prognostic factors in determining the incidence rate. Therefore, they must be considered in the selection of treatment plan and risk stratification.

Colorectal cancer (CRC) is a globally growing disease with a steady decrease in the age of incidence. Pathogenesis of this cancer stems from a complex interaction between environmental factors and genetic predisposition. Among genetic factors, high activity of cyclin D1gene is prominent. A polymorphism (G870A) in exon 4 of cyclin D1 is responsible for a variant transcript with longer half-life and may culminate in uncontrollable cellular growth, thereby contributing to cancer development.

This case-control study evaluated the frequency of CCND1 G870A polymorphism and risk of sporadic CRC in an Iranian population. The study population comprised 50 CRC patients and 50 CRC-free controls selected on the basis of colonoscopy examination. For genotyping, we performed polymerase chain reaction – restriction fragment length polymorphism analysis (PCR-RFLP).

AA genotype frequencies compared to GA+GG genotype frequencies between cases and controls showed that AA genotype frequency in the case group was significantly higher than the control group (AA vs. GG + GA: OR= 2.25, 95% CI: 1.13-5.54, P=0.04). Allele A frequency was 57% in patients and 46% in healthy subjects. Statistical analysis showed that the odds ratio of carriers with allele A for risk of CRC was 1.55 more than G allele carriers (OR=1.55, 95% CI: 0.856-2.828). Moreover, physical activity in cases was significantly less than controls (P=0.001). We further observed that the subjects in the case group used fewer non-steroidal antiinflammatory drugs compared to healthy controls (P=0.02). Analysis of body mass index (BMI) between cases and controls revealed that the average of BMI in cases was higher than the controls (P =0.04).

Our results showed that individuals carrying the AA genotype ran a higher risk of developing CRC compared to GG genotype.

Breast metastases stemming from extramammary malignancies are rare, occurring in approximately 1.3–2.7% of breast malignancies. The most prevalent are metastases belonging to the primary carcinoma of the contralateral breast, followed by lymphoma and malignant melanoma. Breast metastasis is to be suspected in patients with previous history of malignant melanoma who present with a breast mass. Distinguishing metastasis from primary breast neoplasms is a challenging task. Accurate diagnosis is crucial because the prognosis and management differ significantly between primary and secondary malignancies of the breast. Imaging features are non-specific on mammography and ultrasound. There have been several reports on the magnetic resonance imaging (MRI) characteristics of breast metastasis originating from malignant melanoma; however, only few studies have described the diffusion weighted imaging (DWI) feature and the apparent diffusion coefficient (ADC) value. In this study, we report the multimodality imaging features of three cases of breast metastases from malignant melanoma. We particularly focus on MRI findings, such as DWI feature and ADC value and compare them with the MRI features reported in the literature.

Thrombosis is a rare complication of acute lymphoblastic leukemia usually occurring following chemotherapy. The most common reported site is intracranial thrombosis. We reported a case of acute lymphoblastic leukemia with right atrial thrombosis and pulmonary embolism at diagnosis. This diagnosis is important as it can greatly contribute to morbidity and mortality in acute lymphoblastic leukemia patients.