Prognostic value of Osteopontin (SPP1) in colorectal carcinoma requires a personalized molecular approach.

Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade (p = 0.008), tumor invasion (p = 0.01), and distant metastasis (p = 0.04). Kaplan-Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression (p = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker (p = 0.02). However, nuclear SPP1 expression did not show any prognostic value (p = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes' assessment is highly recommended toward precision oncology.

An explanatory mixed methods study on the validity and validation of students' assessment results in the undergraduate surgery course.

BACKGROUND/PURPOSE: There is inadequate evidence of reported validity of the results of assessment instruments used to assess clinical competence. This study aimed at combining multiple lines of quantitative and qualitative evidence to support interpretation and use of assessment results. METHOD: This study is a mixed methods explanatory research set in two stages of data collection and analysis (QUAN : qual). Guided by Messick's conceptual model, quantitative evidences as reliability and correlation coefficients of various validity components were calculated using students' scores, grades and success rates of the whole population of students in 2012/2013 and 2013/2014 (n= 383; 326). The underlying values that scaffold validity evidences were identified via Focus Group Discussions (FGD) with faculty and students; sampling technique was purposive; and results were analyzed by content analysis. RESULTS: (1) Themes that resulted from content analysis aligned with quantitative evidences. (2) Assessment results showed: (a) content validity (table of specifications and blueprinting in another study); (b) consequential validity (positive unintended consequences resulted from new assessment approach); (c) relationships to other variables [a statistically significant correlation among various assessment methods; with combined score (0.64-0.86) and between mid and final exam results (r = 0.672)]; (d) internal consistency (high reliability of MCQ and OSCE: 0.81, 0.80); (3) success rates and grades distribution alone could not provide evidence to advocate an argument on validity of results. CONCLUSION: The unified approach pursued in this study created a strong evidential basis for meaningful interpretation of assessment scores that could be applied in clinical assessments.

Membranous or Cytoplasmic HER2 Expression in Colorectal Carcinoma: Evaluation of Prognostic Value Using Both IHC & BDISH.

BACKGROUND: Human epidermal growth factor recptor-2 (HER2) was identified as a driver gene in several types of cancers with both prognostic and predictive value. However, the molecular association of HER2 gene mutation with HER2 gene amplification and/or protein expression in cancer tissues has not been clearly defined. Moreover, there is little information available on HER2 status role in tumor progression and metastasis in colorectal carcinoma (CRC) compared to other solid tumors. The aim of this study was to evaluate both HER2 amplification and protein expression profiles using immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) techniques, respectively. PATIENTS AND METHODS: Tissue microarray (TMA) was constructed to accommodate a total of 243 CRC formalin-fixed paraffin embedded (FFPE) samples of consent patients and stained by IHC and BDISH methods. The expression patterns of HER2 protein status were evaluated and correlated to HER2 gene amplification status and then assessed for its prognostic value. RESULTS: The expression profile of 58% samples showed cytoplasmic expression patterns of different categories. Interestingly, only 1% showed strong (+3) membranous expression pattern of HER2 with perfect match with their corresponding gene amplification status (>2). However, the cytoplasmic HER2 protein status did not show significant correlation with most clinicopathological features and survival outcomes except with age (p = 0.04) and tumor size (p = 0.03). CONCLUSION: We demonstrated that the membranous HER2 gene/protein status is infrequent, while the main fraction of HER2 overexpression was cytoplasmic and lacking prognostic value. This cytoplasmic HER2 overexpression was induced through a gene-amplification independent pathway, making the HER2 gene status evaluation approach in those cases not worthy. Further investigations about the molecular pathways of the cytoplasmic HER2 protein in CRC and its associations with survival outcomes are required to allow either a breakthrough in CRC management; or to confirm the hypothesis of a marginal role in CRC onset and progression.

Religiosity and Telomere Length in Colorectal Cancer Patients in Saudi Arabia.

Numerous studies have reported a significant relationship between psychological stress, depression, and telomere length (TL), an indicator of cellular lifespan. Religious involvement, which is associated with lower levels of stress and depression, has also recently been related to TL. To our knowledge, this relationship has not yet been examined in Muslims, colorectal cancer patients, cancer patients more generally, or any population outside the USA. A convenience sample of 50 colorectal patients was recruited from hospital-based oncology clinics in Jeddah, Saudi Arabia. Religious involvement was assessed with the 13-item Muslim Religiosity Scale. Social and psychological mediators were measured using established scales. TL was determined from whole-blood leukocytes using quantitative PCR technology. Bivariate analyses indicated a positive but nonsignificant relationship between religiosity and TL (r = 0.13, p = 0.35). Controlling for age, did not affect the relationship (B = 15.6, SE = 17.3, p = 0.37), nor did controlling for other demographic, social or psychological factors. Religious involvement was unrelated to TL in this small sample of colorectal patients. Future cross-sectional and prospective studies in different populations with larger samples are needed.

Health rights knowledge among medical school students at King Abdulaziz University, Jeddah, Saudi Arabia.

BACKGROUND: Health care is a basic human right, and Saudi Arabia affirms these rights for all its citizens. OBJECTIVES: To assess the knowledge of medical students regarding health rights in Saudi Arabia. METHODS: This cross-sectional study was conducted at King Abdulaziz University (KAU) from September 2015 through November 2015. A questionnaire written in English collected demographic data and included questions about reproductive health care and health rights of women and patients with cancer, senility, or special needs. RESULTS: Of the 267 participants, 184 (68.9%) were female, and 252 (94.4%) were Saudi. Regarding consent, 87 (32.6%) and 113 (42.3%) participants believed a female patient required the consent of a male guardian to receive medical treatment or surgery, respectively, in Saudi Arabia, and only 106 (39.7%) knew that a female patient could provide consent for a caesarean section. Sixty-six (24.7%) believed that abortion is never allowed in Islam. Only 93 (34.8%) were aware that acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) patients had health rights, about half (144, 53.9%) knew that cancer patients have a right to full information, and most (181, 67.8%) believed that a patient had the right to withhold health information from his/her family. Approximately half were aware that cancer patients have the right to free medical treatment (138, 51.7%) or that health rights applied to special needs patients (137, 51.3%) and senile patients (122, 45.7%). CONCLUSIONS: The knowledge of KAU medical students regarding health rights of certain patient populations highlights the importance of health rights education in medical school.

p16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma.

BACKGROUND/AIMS: p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC). PATIENTS AND METHODS: Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed. RESULTS: Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325). CONCLUSION: Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target.

Clinical significance of frequent somatic mutations detected by high-throughput targeted sequencing in archived colorectal cancer samples.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease with different molecular characteristics associated with many variables such as the sites from which the tumors originate or the presence or absence of chromosomal instability. Identification of such variables, particularly mutational hotspots, often carries a significant diagnostic and/or prognostic value that could ultimately affect the therapeutic outcome. METHODS: High-throughput mutational analysis of 99 CRC formalin-fixed and paraffin-embedded (FFPE) cases was performed using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™ platform. Correlation with survival and other Clinicopathological parameters was performed using Fisher's exact test and Kaplan-Meier curve analysis. RESULTS: Targeted sequencing lead to the identification of frequent mutations in TP53 (65 %), APC (36 %), KRAS (35 %), PIK3CA (19 %), PTEN (13 %), EGFR (11 %), SMAD4 (11 %), and FBXW7 (7 %). Other genes harbored mutations at lower frequency. EGFR mutations were relatively frequent and significantly associated with young age of onset (p = 0.028). Additionally, EGFR or PIK3CA mutations were a marker for poor disease-specific survival in our cohort (p = 0.009 and p = 0.032, respectively). Interestingly, KRAS or PIK3CA mutations were significantly associated with poor disease-specific survival in cases with wild-type TP53 (p = 0.001 and p = 0.02, respectively). CONCLUSIONS: Frequent EGFR mutations in this cohort as well as the differential prognostic potential of KRAS and PIK3CA in the presence or absence of detectable TP53 mutations may serve as novel prognostic tools for CRC in patients from the Kingdom of Saudi Arabia. Such findings could help in the clinical decision-making regarding therapeutic intervention for individual patients and provide better diagnosis or prognosis in this locality.

Development of natural sorbent based micro-solid-phase extraction for determination of phthalate esters in milk samples.

In the present study, a natural sorbent based micro-solid phase extraction (µ-SPE) was developed for determination of phthalate esters in milk samples. For the first time, an efficient and cost effective natural material (seed powder of Moringa oleifera) was employed as sorbent in µ-SPE. The sorbent was found to be naturally enriched with variety of functional groups and having a network of interconnected fibers. This method of extraction integrates different steps such as removal of proteins and fatty stuff, extraction and pre-concentration of target analytes into a single step. Thirteen phthalate esters were selected as target compounds for the development and evaluation of method. Some key parameters affecting the extraction efficiency were optimized, including selection of membrane, selection and amount of sorbent, extraction time, desorption solvent, volume of desorption solvent, desorption time and effect of salt addition. Under the optimum conditions, very good linearity was achieved for all the analytes with coefficient of determinations (R(2)) ranging between 0.9768 and 0.9977. The limits of detection ranged from 0.01 to 1.2 µg L(-1). Proposed method showed satisfactory reproducibility with relative standard deviations ranging from 3.6% to 10.2% (n = 7). Finally, the developed method was applied to tetra pack and bottled milk samples for the determination of phthalate esters. The performance of natural sorbent based µ-SPE was better or comparable to the methods reported in the literature.

High expression of matrix metalloproteinases: MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma.

AIM: To evaluate the expression pattern of matrix metalloproteinases (MMPs); MMP-2, MMP-7 and MMP-9 in colorectal cancer (CRC) and determine its prognostic potential. PATIENTS & METHODS: CRC samples of 127 patients were studied. Protein expressions of MMP-2, -7 and -9 were analyzed by immunohistochemistry and association with clinicopathological variables was statistically analyzed. RESULTS: Overexpressions of MMP-2 and MMP-9 correlated with poor outcome as evaluated by univariate Kaplan-Meier for disease-free survival (p = 0.04, p = 0.0001) and disease-specific survival (p = 0.01, p = 0.01), respectively. Cox analysis of MMP-2 and -9 were significant independent predictors of disease-free survival (p = 0.006, p = 0.018) and disease-specific survival (p = 0.004, p = 0.049), respectively. CONCLUSION: MMPs expression patterns provide useful prognostic information in CRC, while predicting the patients at high risk for recurrent disease.

Breast Cancer Knowledge Among Male High School Students in Saudi Arabia.

Breast cancer (BC) accounts for 24 % of all women cancer cases diagnosed in Saudi Arabia each year. Awareness is extremely important in combating this disease. This study was undertaken to assess male high school students' response to BC. This cross-sectional survey was performed on male high school students across schools in Jeddah. A questionnaire gathered data on respondent demographics, beliefs about BC, BC risk factors, early screening methods, and role of men in BC. Statistical analysis was done using SPSS 20. A total of 824 students participated, with an average age of 17.0 years. There was more than 50 % agreement that early detection of BC enhances the chances of recovery, that BC is treatable, and that clinical breast examination and breastfeeding provide protection from BC. Around half the survey population thought that BC was fatal and contagious. Fewer than 50 % thought that BC was inherited and related to smoking, consumption of contraceptive pills, repeated exposure to radiation, obesity, and wearing a bra and that breast tumors were all malignant and spread to different parts of the body. Others knew that mammograms should be performed periodically. A high percentage persuaded their relatives to have mammograms and provided them with psychological support. Knowledge of BC among male high school students in Saudi Arabia is still limited, and, therefore, programs and activities need to be established to increase awareness among high school students.

Religious beliefs, practices, and health in colorectal cancer patients in Saudi Arabia.

OBJECTIVE: Colorectal cancer (CRC) patients experience considerable psychological stress because of changes brought on by their illness. Religion may be a resource for such patients. We examined the prevalence of religious beliefs and practices in CRC patients and correlation with demographic, social, psychological, and physical health characteristics. METHODS: Seventy CRC patients (all Muslim) in Jeddah, Saudi Arabia, were surveyed using a 13-item Muslim religiosity scale. Standard measures were used to assess depressive symptoms, depressive disorder, and social support; demographic and social factors, psychiatric history, and disease factors were also measured. RESULTS: All 70 participants (100%) engaged in group worship and prayer (Fard) five times/day, and 75.7% never skipped or combined two or more obligatory prayers; 71.4% read or recited the Qur'an several times/week or daily; 80.0% gave money to the poor each year (Zakat); 71.4% fasted throughout the month of Ramadan (Sawm) and other times as well; 91.4% said they 'definitely' experienced the presence of Allah; and 74.3% said their entire approach to life was definitely based on their religious beliefs. Overall religiosity was inversely related to depressive symptoms (B = -0.58, SE = 0.30, p = 0.026) and suicidal ideation (B = -0.07, SE = 0.03, p = 0.025), after controlling for financial status and social factors. CONCLUSIONS: Religious involvement was widespread in this sample of CRC patients in Saudi Arabia and was related to fewer depressive symptoms and less suicidal ideation. No relationship was found with stage of disease or duration of treatment.

Impact of Physiological Symptoms and Complications of Colorectal Cancer on the Quality of Life of Patients at King Abdulaziz University Hospital.

Colorectal cancer (CRC) is common worldwide. The high prevalence of the disease raises concerns about how CRC influences the health-related quality of life (QoL). To explore the impact of physiological symptoms and complications of CRC on patients' QoL, we conducted a cross-sectional survey using the FACT-C self-report instrument. The chi-square test was used to compare qualitative data. We found that pain was reported by most of the patients (n = 31; 77.5 %). Furthermore, male patients were more likely to complain of pain "mostly" as compared with females (P = .032). We found no significant differences between genders regarding general health-related questions. A greater proportion of male patients often complained of abdominal cramps (P = .542), weight loss (P = .086), and diarrhea (P = .408). More than half of the patients (n = 26; 65 %) reported having a good appetite; a greater proportion of males reported having a good appetite "mostly" (P = .014). Social and psychological qualities of life were not significantly different between male and female patients. Male and female patients did not differ in their report of disease acceptance (P = .420) and ability to enjoy life (P = .744). No difference was also found between genders regarding contentment with QoL (P = .793) or ability to sleep well (P = .695). Furthermore, there were no differences between genders regarding job fulfillment (P = .272). Our results add to the growing body of knowledge about the effect of CRC on QoL. Importantly, the differences in self-reported pain and appetite between male and female patients in our study suggest the importance of gender-based treatments in improving patients' QoL.

c-MET immunostaining in colorectal carcinoma is associated with local disease recurrence.

BACKGROUND: Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumour progression. The aim of the present study is to explore the relationship between immunohistochemical expression of c-MET in colorectal carcinoma (CRC) and the clinicopathological characteristics and follow up data, to compare the expression of c-MET in primary CRC and its metastasis in lymph nodes and to test its validity as independent prognostic factor. METHODS: Hundred and thirty-five archival CRC and nodal metastases samples were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed and immunohistochemistry was done to detected c-MET protein expression. Appropriate statistical analysis was performed. RESULTS: High c-MET immunostaining was significantly associated with tumour size larger than 5 cm (p < 0.003) and in left colon subsite (p < 0.05). There was no significant correlation between c-MET protein expression and age, sex, degree of differentiation, tumour invasion, presence of nodal metastasis, lymphovascular invasion, status of surgical resection margin, or presence of distant metastasis. Furthermore, no association between c-MET protein expression and disease free survival. High protein expression of c-MET is associated with the incidence of local disease recurrence (p < 0.012). CONCLUSION: c-MET is a new promising target that may help in understanding the pathogenesis of CRC, and to be used as independent prognostic biomarker to predict local disease recurrence in CRC. Further molecular in vitro and in vivo studies are required to pursue c-MET as potential molecular marker of metastases and test the possibility of its incorporation as a new targeted therapeutic target.

Overexpression of PAK-1 is an independent predictor of disease recurrence in colorectal carcinoma.

BACKGROUND: Colorectal carcinoma (CRC) is a significant cause of major morbidity and mortality. PAK-1 is a protein that regulates cytoskeletal dynamics and cell motility. The purpose of the present study is to investigate the relationship between PAK-1 immunoexpression and CRC progression and its validity as an independent prognostic factor. PATIENTS AND METHODS: Paraffin blocks of 103 primary CRCs and 37 nodal metastases were retrieved and tissue microarrays were constructed. Immunohistochemistry was performed using anti-PAK-1 antibody. Immunostaining was scored and results were analysed in relation to clinicopathological parameters. RESULTS: PAK-1 was overexpressed in primary CRC (P<0.001). No difference between low and high expression in nodal metastasis (P=0.139). There was no difference between PAK-1 immunoexpression in primary and nodal metastasis (P=0.275). High PAK-1 immunoexpression was associated with disease recurrence (P=0.03). However, there was no association with most clinicopathological parameters. PAK-1 overexpression was detected as an independent predictor of disease recurrence (P=0.05). No association was found between PAK-1 immunoexpression and disease free survival (log-rank =1.287, P=0.257). CONCLUSION: PAK-1 overexpression may be involved in CRC progression and could be considered an independent predictor of disease recurrence. Further in vivo and in vitro molecular studies are needed to investigate the role of PAK-1 in colorectal carcinogenesis.

Immunoexpression of cyclin D1 in colorectal carcinomas is not correlated with survival outcome.

BACKGROUND: Colon and colorectal cancer (CRC) research has entered a new era with recent updates of molecular events and prognostic markers. Among other prognostic markers, exaggerated expression of nuclear CCND1 has key role in tumour pathogenesis and metastases of CRC and has also been claimed to predict response to treatment. OBJECTIVES: This study was designed to evaluate the prognostic and predictive value of CCND1 in CRC and the correlation of CCND1 expression with the different clinicopathological parameters. METHODS: Paraffin blocks from 117 primary CRC were retrieved from the archives of the Department of Pathology at King Abdulaziz University. Tissue microarrays were designed and constructed. The immunostaining of CCND1 was performed and analysed. RESULTS: There were more cases with low nuclear immunoexpression of CCND1 in both primary tumours and nodal metastasis (p <0.001). Cyclin D1 did not show association with clinicopathological features except with lymphovascular invasion. Low nuclear immunoexpression of CCND1 was associated with negative lymphovascular invasion (p = 0.046). There was no statistically significant correlation between CCND1 immunoexpression and survival probability (Log Rank = 2.474, p = 0.116). CONCLUSION: Our study indicates that CCND1 immunoexpression cannot be used as a predictor of survival in CRC. It also shows no significant correlation with clinicopathological features except with lymphovascular invasion.

The significance of sonic hedgehog immunohistochemical expression in colorectal carcinoma.

Colorectal carcinoma is a significant source of major morbidity and mortality. Sonic hedgehog (Shh) is expressed in normal gastrointestinal tract mucosa and in many malignancies. The purpose of the present study is to investigate the relationship between Shh immunoexpression in CRC and clinicopathological characteristics. Paraffin blocks of 155 primary CRCs and 37 nodal metastases were retrieved and tissue microarrays were constructed. Immunohistochemistry was performed using anti-Shh antibody. Immunostaining was scored and results were analysed in relation to the clinicopathological parameters. Shh was overexpressed in primary CRC (p = 0.02) and in nodal metastasis (p = 0.004). There was no difference between Shh immunoexpression in primary CRC and in nodal metastasis (p = 0.941). High Shh immunoexpression was associated with well differentiated tumours (p = 0.004). However, there was no association with other clinicopathological parameters. Shh overexpression was not associated disease free survival (log-rank = 0.079, p = 0.778). Shh is overexpressed in well differentiated CRC. However, Shh is not associated with other clinicopathological and prognostic factors. Loss of Shh may be associated with proliferation and loss of differentiation in CRC. Further molecular studies are required to address the potential importance of Shh signalling in CRC and to test Shh inhibitors and activators as potential therapeutic targets in CRC.

Depression in patients with colorectal cancer in Saudi Arabia.

OBJECTIVE: Persons with colon cancer experience considerable psychological stress due to physical and social changes brought on by illness, increasing their risk of depressive disorder (DD). We examine the prevalence of DD and depressive symptoms and determine baseline demographic, social, psychological, and physical health correlates. METHODS: A convenience sample of 70 cancer patients in Jeddah, Saudi Arabia, was screened for DD using an abbreviated version of the Structured Clinical Interview for Depression (SCID) and for depressive symptoms using the Hamilton Depression Rating Scale (HDRS). Demographic, psychosocial, psychiatric, and physical health characteristics were also assessed, along with past treatments for colon cancer. Bivariate and multivariate analyses identified predictors of DD and symptoms. RESULTS: The 1-month prevalence of DD was 30.0% (12.9% major depression, 5.7% minor depression, and 11.4% for dysthymia) and significant depressive symptoms were present in 57.1% (HDRS 8 or higher), including having persistent suicidal thoughts for 2 weeks or longer wthin the past month (14.3%) . Low social support and having a co-morbid psychiatric illness (particularly anxiety) independently predicted DD based on the SCID. Saudi nationality, poor financial situation, low social support, and co-morbid psychiatric illness independently predicted depressive symptoms on the HDRS. Surprisingly, stage of cancer, duration of cancer, and treatments for cancer were unrelated to DD or depressive symptoms. CONCLUSIONS: DD and significant depressive symptoms are common in patients with colon cancer in Saudi Arabia, and are predicted by a distinct set of demographic and psychosocial risk factors that may help with identification. Demographic and psychological risk factors were more likely to be associated with depression than cancer characteristics in this sample.

Prognostic significance of VEGFR1/Flt-1 immunoexpression in colorectal carcinoma.

Colorectal carcinoma (CRC) is a major cause of morbidity and mortality. Vascular endothelial growth factor 1/Fms-like tyrosine kinase 1 (VEGFR1/Flt-1) regulates monocyte migration, recruits endothelial cell progenitors, increases the adhesive properties of natural killer cells and induces of growth factors. Flt-1 is expressed on tumour cells and has been implicated in tumour growth and progression. The objective of this study is to address the relation of Flt-1 expression to tumour prognostication. Paraffin blocks from 143 primary CRC and 48 regional nodal metastases were retrieved from the archives of the Department of Pathology at King Abdulaziz University. Tissue microarrays were designed and constructed. Immunohistochemistry for Flt-1 was performed. Staining intensity and extent of staining were assessed and combined. Results were dichotomised as low expression and high expression. Flt-1 was overexpressed in primary tumours and nodal metastasis (p < 0.001 and 0.001) with no difference between primary and nodal metastasis (p = 0.690). Flt-1 immunoexpression was not associated with the clinicopathological parameters. Flt-1 overexpression was an independent predictor of positive margin status, positive lymphovascular invasion and local disease recurrence (p < 0.001, p < 0.001 and p = 0.003, respectively). Flt-1 was not associated with survival (log-rank = 0.003, p = 0.959). Flt-1 was overexpressed in primary CRC and their nodal metastases. Flt-1 expression was an independent predictor of margin status, lymphovascular invasion and local disease recurrence. Therefore, expression profiling of Flt-1 seems to have a prognostic potential in CRC. However, to elucidate the association of overexpression of Flt-1 with tumour characteristics and prognostication, more in vivo and in vitro molecular investigations are recommended.

Loss of villin immunoexpression in colorectal carcinoma is associated with poor differentiation and survival.

Background and Aims. Villin is a highly specialised protein and is expressed in intestinal and renal proximal tubular epithelium. It was detected in colorectal carcinomas (CRC) and other nongastrointestinal tumours. The aim of the current study is to investigate the immunohistochemical expression of villin in a subset of primary CRC and determine its relation to tumour differentiation, invasion, nodal metastasis, recurrence, and disease-free survival. Patients and Methods. Paraffin blocks of 93 cases of CRC were retrieved constituting 93 primary CRC and 58 adjacent normal mucosa. Immunohistochemistry was performed using antivillin antibody. The extent (%) of villin immunoexpression was categorised for statistical analysis. Statistical tests were used to determine the association of villin with clinicopathological characteristics: age, sex, tumour location, tumour size, depth of invasion, tumour grade, nodal metastasis, lymphovascular invasion, margin status, recurrence, and survival. Results. Villin immunostaining results showed that villin is downregulated in CRC. Villin has no association with age, sex, tumour location, depth of invasion, nodal metastasis, lymphovascular invasion, margin status, and recurrence. However, villin is expressed in higher rate in CRC less than 5 cm, well- and moderately differentiated CRC. Poor survival was associated with tumour with low villin immunoexpression. Conclusion. Villin was downregulated in CRC. Villin immunoexpression in CRC is associated with better survival, well-differentiated tumours, and small-sized tumours. Villin has no significant association with disease recurrence or nodal metastasis. More in vivo and in vitro studies are required for further elucidation of how villin may be involved in CRC.