Papers by Mahmoud Al-ahwal

BMC Cancer, 2015
Background: Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several... more 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.

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association, 2005
Data of all patients with CRC treated at two hospitals in the Western region of the Kingdom of Sa... more Data of all patients with CRC treated at two hospitals in the Western region of the Kingdom of Saudi Arabia (KSA), between 1993 and 2002, were collected and analyzed. Out of the 121 patients evaluated, ten were excluded because of incomplete data. Out of 111 patients, 59 (53.2%) were males, with a male to female ratio of 1.13: 1 and 49 (44.1 %) were Saudis. Thirty-three patients (29.7%) were 40 years or less and 78 (70.3%) were more than 40 years. Colon cancer was found in 69 patients (62.2%) and rectal cancer in 42 (37.8%). Stages at presentation were; stage 0 (2.7%), stage I (11.7%), stage II (23.4%), stage III (20.7%), stage IV (22.5%) and the staging was unknown in 18.9% of the patients. The most common tumor grade was moderately differentiated (38.7%), followed by poorly differentiated (20.7%) and well differentiated 19.8% of the patients. Forty-four patients (39.6%) were alive at the time of data collection, 43 (38.7%) expired and 24 (21.6%) were lost to follow up. Correlation...

Anticancer research, 2012
CD44 is a transmembrane glycoprotein and is associated with cell-matrix and cell-cell interaction... more CD44 is a transmembrane glycoprotein and is associated with cell-matrix and cell-cell interactions. CD44 expression was shown to be relevant to tumour progression in various types of human cancer. The objective of this study was to investigate the relationship between the expression levels of the standard form of CD44 (CD44s), and clinicopathological characteristics in a subset of colorectal carcinomas (CRC). A total of 96 cases of CRC were retrieved from the archives at the Department of Pathology at King Abdulaziz University, Jeddah, KSA. Immunohistochemistry was performed using antibodies to CD44s. A cut-off of <10% of positive neoplastic cells was used to define low expression, 10-50% to define moderate expression and >50% to define extensive expression. Statistical tests were used to determine the association of CD44s with clinicopathological characteristics in a subset of colorectal carcinomas and survival. Immunostaining results showed that there was no association betw...

JPMA. The Journal of the Pakistan Medical Association, 2006
To review HER-2 status and its correlation with all other prognostic histopathological features o... more To review HER-2 status and its correlation with all other prognostic histopathological features of all Breast Cancer (BC) patients diagnosed between January 2000 and December 2004 at King Abdul Aziz University Hospital (KAUH) in the western region of Saudi Arabia. Histopathology specimens were examined by Immunohistochemistry (IHC) and labeled as HER-2/neu positive when Hercep Test score was three plus (3+). HER-2/neu was reported only in 145 patients out of 260. Out of 145 patients, it was positive in 41 patients (28.3%), negative in 104 patients (71.7%). Correlations between HER-2/neu status and age, race and other prognostic histopathologic features revealed: No correlation with age (or < or = 40 Y vs >40 Y with a p-value of 0.552), race (Saudis vs Non-Saudis with a p-value of 0.133), histopathology subtype (p=0.980), tumor size (p=0.455), number of positive lymph nodes (p=0.660), tumor grade (p=0.062), lymphovascular invasion (p=0.055) and progesterone receptor (PR) status...

Life Science Journal
Introduction: TTF-1 is a helpful marker for primary lung adenocarcinoma and is considered as a re... more Introduction: TTF-1 is a helpful marker for primary lung adenocarcinoma and is considered as a reliable marker to distinguish between primary and secondary lung carcinoma. However, some studies showed that TTF-1 also can be expressed in extrapulmonary adenocarcinomas. The data on TTF-1 expression in endometrial cancer is limited and conflicting. The aim of this study is to evaluate the immunoexpression of TTF-1 in primary endometrial adenocarcinoma. Material and methods: Tissue microarrays were prepared from archival of endometrial carcinoma obtained from the Department of Pathology at King Abdulaziz University Jeddah, Saudi Arabia. Tissue sections were immunostained using monoclonal antibodies to TTF-1. The immunohistochemical stains were scored semiquantitativly from 0 to 5+. Results: The categories of endometrial adenocarcinoma include 78 grade I endometrioid, 17 grade II endometrioid, 12 grade III endometrioid, 7 serous, 2 clear cell. TTF-1 immunoexpression was detected only in ...

Journal of Microscopy and Ultrastructure, 2013
Background: Osteopontin (OPN) is expressed in various malignancies and may play an important role... more Background: Osteopontin (OPN) is expressed in various malignancies and may play an important role in tumorigenesis, tumour invasion, and metastasis in various malignancies including thyroid cancers. The objective of this study was to investigate the relationship between OPN immunoexpression and clinicopathological characteristics in thyroid lesions. Material and methods: Paraffin blocks belonging to 160 patients with thyroid neoplasms were retrieved from the archive of the Department of Pathology at King Abdulaziz University, and King Faisal Specialist Hospital, Jeddah, Saudi Arabia. Immunohistochemistry was performed using anti-OPN antibody. Statistical tests were used to determine the relation of OPN immunoexpression to clinicopathological characteristics and survival. Results: Immunostaining results showed that OPN was localised in the cytoplasm and nucleus with higher cytoplasmic expression. Cytoplasmic and nuclear OPN was higher in thyroid cancer than other lesions. Microcarcinoma variant of papillary thyroid carcinoma showed a lower OPN cytoplasmic level than other variants. OPN cytoplasmic expression was not associated with most of the clinicopathological parameters tests. However, OPN cytoplasmic overexpression was associated poor survival outcome (p < 0.001). Conclusion: Upregulation of cytoplasmic OPN was associated with poor survival outcome and was an independent predictor of margin involvement and recurrence. Nuclear OPN expression was lower than cytoplasmic and was associated with extrathyroid extension of thyroid cancer. OPN plays a role in thyroid carcinoma and incoming research has to be focused on the mechanistic association with invasion and metastasis.
Tumor Biology, 2014
Your article is protected by copyright and all rights are held exclusively by International Socie... more Your article is protected by copyright and all rights are held exclusively by International Society of Oncology and BioMarkers (ISOBM). This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".

ISRN Gastroenterology, 2013
Background and Aims. Villin is a highly specialised protein and is expressed in intestinal and re... more 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.
Journal of King Abdulaziz University-Medical Sciences, 1999
Objective: To assess the results of chemoembolization in this pilot study for patients with unres... more Objective: To assess the results of chemoembolization in this pilot study for patients with unresectable metastatic liver neoplasms.
Journal of …, 2011
Background Recent studies suggest that aberrations in cell cycle checkpoint controllers are a com... more Background Recent studies suggest that aberrations in cell cycle checkpoint controllers are a common feature in human malignancies and predict prognosis independent of stage. Objectives This study correlated two cell cycle regulators (p27 and ...

Background: Colorectal cancer (CRC) is the second most common malignancy in the Saudi population.... more Background: Colorectal cancer (CRC) is the second most common malignancy in the Saudi population. This study aimed to review CRC data from the Saudi Cancer Registry (SCR) in order to evaluate the prognostic factors for CRC survival in Saudi patients. Methods: This study was a retrospective censored overall survival (OS) analysis of CRC data for the period 1994-2004 obtained from the SCR. Data were collected from all 13 administrative regions of the Kingdom of Saudi Arabia (KSA) by the SCR in collaboration with the National Information Center of the Ministry of Interior. The Kaplan-Meier method was used to calculate the cumulative survival rate, which was then stratified by gender and by period (1994-1999 versus 2000-2004). The clinico-pathological variables that might affect CRC survival were analyzed by Cox regression analysis. Results: Between 1994 and 2004, 549 CRC cases were diagnosed (363 [66.1%] in males and 186 [33.9%] in females). The OS for CRC during this period was 44.6% (44.7% for 1994-1999 and 44.3% for 2000-2004 [p=0.7]). There was a significant (p=0.003) discrepancy of 9.6% between the male five-year OS (41.0%) and the female five-year OS (50.6%). The five-year OS was 63.3% for patients with localized disease, 50.2% for those with regional disease, and 14.7% for patients with metastases. By Cox regression analysis, age and extent were significant prognostic factors of survival in patients with colon cancer; the risk was higher in patients with distant metastasis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.17-5.45; p=0.01). In patients with rectal cancer, the risk was lower in males (HR, 0.66; CI, p=0.04), but higher in patients with unknown tumor extent (HR, 3.70; 95% CI, 1.66-8.24; p=0.01). Conclusions: The five-year OS for 1994-2004 was 44.6% for patients with CRC. More so, five-year OS based on CRC stage was generally lower than the typically reported survival rates. The establishment of a national screening program and increased access to specialized medical faculties may be necessary to improve CRC survival in the KSA.

Seikagaku, 2006
Hfq is a highly conserved pleiotropically acting prokaryotic RNA-binding protein involved in the ... more Hfq is a highly conserved pleiotropically acting prokaryotic RNA-binding protein involved in the post-transcriptional regulation of many stress-responsive genes by small RNAs. In this study, we show that Hfq of the strictly human pathogen Neisseria meningitidis is involved in the regulation of expression of components involved in general metabolic pathways, iron metabolism and virulence. A meningococcal hfq deletion strain (H44/76Dhfq) is impaired in growth in nutrient-rich media and does not grow at all in nutrient-limiting medium. The growth defect was complemented by expression of hfq in trans. Using proteomics, the expression of 28 proteins was found to be significantly affected upon deletion of hfq. Of these, 20 proteins are involved in general metabolism, among them seven iron-responsive genes. Two proteins (PilE, TspA) are involved in adherence to human cells, a step crucial for the onset of disease. One of the differentially expressed proteins, GdhA, was identified as an essential virulence factor for establishment of sepsis in an animal model, studied earlier. These results show that in N. meningitidis Hfq is involved in the regulation of a variety of components contributing to the survival and establishment of meningococcal disease.

Modern Pathology
The current staging system along the conventional prognostic factors is the gold standard for pro... more The current staging system along the conventional prognostic factors is the gold standard for prognosis of colorectal cancer (CRC). In spite of that, it is unable to distinguish those patients who might carry high risk of recurrence and poor outcome, which highlights the need for new molecular factors that could stratify patients into different risk categories. This study is aimed to assess the expression of selected group of matrix metalloproteinases (MMPs); MMP-2, MM-7 and MMP-9 in a subset of primary CRC and determine its relation to different clinico-pathological factors and survival. Paraffin blocks of 127 CRC patients were retrieved. Antigen expressions of MMP-2 and -9 were analyzed by immunohistochemistry (IHC) and their cytoplasmic and stromal staining was evaluated. The results showed that overexpressions of both MMP-2 and MMP-9 were a significant sign of poor outcome and recurrence as evaluated by univariate Kaplan–Meier for disease-free survival (DFS) (p= 0.012, p= 0.001)...
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Papers by Mahmoud Al-ahwal