Fibroblast growth factor receptor 2 gene (FGFR2) rs2981582T/C polymorphism and susceptibility to breast cancer in Saudi women.

Fibroblast growth factor receptor 2 is a protein encoded by FGFR2 gene and plays an important role in cellular growth. This study was conducted to investigate a potential association of FGFR2 rs2981582 with breast cancer. DNA was obtained from 137 Formalin-fixed, paraffin-embedded tumors and 98 normal breast tissue samples. Genotypes were carried out with PCR-RFLP. The odds ratio and 95% confidence interval (CI) were used to evaluate the power of the associations. A significant association between FGFR2 rs2981582 C allele and susceptibility to breast cancer was found (p-value < 0.0001, Odds Ratio = 2.3, %95 CI (1.5-3.0). No significant differences in FGFR2 rs2981582 genotypes and alleles distribution among breast patients with different hormonal receptor status (p > 0.05) were detected. However, a significant difference was found in genotypes and alleles distribution in ER+, PR- and HER2 between breast cancer cases and controls. This study showed an association of FGFR2 rs2981582T/C with breast cancer in Saudi women, further large study is required to validate the results.

Murine Double Minute 2 Gene (MDM2) rs937283A/G variant significantly increases the susceptibility to breast cancer in Saudi Women.

Breast cancer is predominant causes of mortality in women worldwide. Genetic polymorphisms have a significant role in breast cancer aetiology. TP53 and its inhibitor the murine double minute 2 (MDM2) genes encode proteins that have crucial functions in the DNA damage response. The allelic variations within these genes could influence the susceptibility to breast cancer. MDM2 promotor polymorphism rs937283A/G has a role in susceptibility to cancer and modifies the promoter activity. In the present case-control study, the association of MDM2 rs937283A/G polymorphism and breast cancer susceptibility in Saudi women with samples of 137 breast cancer patients, and 98 healthy controls were explored. MDM2 gene polymorphism rs937283A/G was genotyped by polymerase chain reaction restriction fragment length polymorphism and confirmed by sequencing. The results revealed that rs937283A/G variant is significantly increases the risk of breast cancer in Saudi women (p-value = 0.0078). Moreover, rs937283A/G polymorphism was associated with high risk of breast cancer in estrogen positive breast cancer patients (p-value = 0.0088), progesterone positive breast cancer patients (p-value = 0.0043), human epidermal growth factor receptor 2 negative breast cancer patients (p-value = 0.0026), and triple negative breast cancer patients where (p-value = 0.0003). Positive association between increased breast cancer risk and rs937283 variant in premenopausal Saudi women, below 50 years of age, was demonstrated (p-value = 0.0023). Collectively, MDM2 rs937283A/G polymorphism could act as a possible biomarker for breast cancer susceptibility in Saudi women.

Estrogen Receptor 1 Gene (ESR1) rs2234693 Polymorphism and Breast Cancer Risk in Saudi Women.

OBJECTIVE: The present study aimed to determine the role of ESR1 gene rs2234693 T/C polymorphism (PvuII) in the susceptibility to breast cancer and to assess the association of this polymorphism within presence or absence of estrogen, progesterone receptors, human epidermal growth factor receptor 2 (HER2) and with premenopausal and postmenopausal age in Saudi women. METHODS: The study was a retrospective case-control study. In this study, 137 breast cancer and 98 normal breast paraffin embedded tissues were included.  DNA was extracted and ESR1 gene rs2234693 T/C polymorphism was genotyped by PCR-RFLP. Genetic association tests were performed. RESULTS: The results showed no significant difference in distribution of rs2234693 T/C alleles and genotypes frequencies. Odd ratios (95% CI) were 1.15 (0.8-1.66) and 1.06 (0.5-1.98) and p values were 0.51 and 0.87, respectively. The genotypes and alleles frequencies within different hormonal receptors groups and ages of menopause showed no signification association   (odd ratios were less or close to 1 and p values > 0.05). CONCLUSION: ESR1 gene rs2234693 T/C polymorphism was not associated with susceptibility to breast cancer and different menopausal, hormone receptors, and HER2 status in breast cancer patients.  Further analysis using larger sample size will be needed to assess the association of different polymorphisms within the gene and risk of breast cancer.

Prognostic Significance of Cyclin D1 Over-expression in Colorectal Cancer: An Experience from Madinah, Saudi Arabia.

Background and study aim: Cyclin D1 is a key regulatory protein in the cell cycle and is over-expressed in many tumors, including endometrial, thyroid, urothelial, breast, brain gliomas, and esophageal cancers. The main aim of the present study is to examine the expression pattern of cyclin D1 and its correlation with the different clinicopathological features in patients with colorectal camcer (CRC) from the Madinah region of Saudi Arabia. Patients and methods: The archival tumor blocks were analyzed using immunohistochemistry for Cyclin D1 over-expression in 324 CRC patients diagnosed from January 2006 to December 2017, at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia. Results: Cyclin D1 over-expression was absent in normal mucosa, while 15% cases of adenoma showed its over-expression. In CRC, Cyclin D1 was expressed at high levels in 24.1% of case. No significant correlation was observed between Cyclin D1 over-expression and age, gender, tumor size, type and location. However, Cyclin D1 over-expression exhibited a significant correlation with tumor differentiation (p=0.04), lymph node involvement (p=0.001), lymphovascular invasion (p=0.001), distant metastasis (p=0.006) and AJCC staging (p=0.001). The Kaplan-Meir analysis revealed a shorter period of survival with Cyclin D1 over-expression (p=0.000). The Cox-regression model analysis showed that Cyclin D1 over-expression was an independent prognostic marker in CRC (p=0.000). Conclusion: Cyclin D1 over-expression increases during normal-adenoma-carcinoma sequence. The significant association observed between Cyclin D1 over-expression, advanced tumor stage and short survival period clearly suggest the role of Cyclin D1 in the carcinogenesis and progression of CRC.

Clinicopathological profile of gastric cancers in Al-Madinah, Saudi Arabia.

OBJECTIVE: To characterise the clinicopathological features of gastric cancer. METHODS: This retrospective study was conducted at the histopathology laboratory of King Fahad Hospital, Madinah, Saudi Arabia, and comprised record of gastric cancer patients from January 2006 to September 2015. Data of all patients who had undergone gastrectomy was included. SPSS 19 was used for data analysis. RESULTS: Of the 63 patients, 42(66.7%) were males while 21(33.3%) were females. The overall mean age was 58.5±14.6years (range: 23-95 years). The mean age of males at diagnosis was greater than the mean ages of females (60.4 ± 15.1vs. 54.5 ± 13.6 years). Adenocarcinoma was the most common histologic type, occurring in 49(77.8%) patients. There were 30(47.6%) cases of intestinal subtype and 19(30.2%) cases of diffuse subtypes of adenocarcinoma. The mean age of patients with intestinal subtype was greater than those with diffuse type (60.2 ± 14.9 vs. 56.8±14.2 years). Younger patients mainly presented with poorly differentiated tumours as compared to elder patients. The most common site of gastric cancer was body 28(44.5%), followed by antrum 12(30.1%). . CONCLUSIONS: Gastric cancer was diagnosed in advanced stages and in young females. Younger patients were more frequently affected by poorly differentiated and diffuse adenocarcinoma.

Histopathological pattern of benign endoscopic gastric biopsies in Western Saudi Arabia: A review of 1236 cases.

OBJECTIVE: To determine the histopathological pattern of gastritis and benign gastric diseases in western Saudi Arabia. METHODS: TThis retrospective histopathology-based study was conducted in a tertiary care hospital in Madinah, Saudi Arabia, and comprised medical records of all patients who were diagnosed to have benign gastric diseases from January 2006 to December 2015.SPSS 19 was used for data analysis. RESULTS: Of the 1,236 patients, 669(54.1%) were males and 567(45.9%)were females. The overall mean age was 43±10.75 years (range: 10-100 years). Besides, 755(61.1%) patients were in the age group of 20-49 years. Gastritis was diagnosed in 1,105(89.4%) cases, 1,091(88.3%) of which were chronic. Benign polypi was found in 34(2.75%) cases and normal biopsies in 97(7.85%) cases. Helicobacter pylori organisms were detected in 402(32.5%) cases. Helicobacter pylori gastritis was active in 331(82.5%) cases, atrophic in 4(0.9%) and metaplastic in 11(2.7%) cases. The mean age of gastric polypi patients was 50.1±12.52 years (range: 16-90 years). Hyperplastic polypi was seen in 30(88.2%) cases. Fundic gland polypi were found in 4(11.8%) cases. CONCLUSIONS: Benign gastric diseases appeared to affect the younger individuals. Gastritis was more prevalent and benign polypi was less so.

Urinary bladder cancer in adults: a histopathological experience from Madinah, Saudi Arabia.

OBJECTIVE: To delineate the frequency and clinicopathological features of urinary bladder cancer. METHODS: This retrospective study was conducted at the King Fahd Hospital, Madinah, Saudi Arabia, and comprised medical records related to bladder tumours, from January 2006 to October 2015. Data was obtained from histopathologic reports and evaluated for age, gender, cystoscopic findings and histopathological characteristics at the time of presentation. RESULTS: Of the 116 cases, 96(82.7%) were of men while 20(17.3%) were of women. The mean age was 62.4±15.62 years (range: 20-115 years). Transitional cell carcinoma was the most common histological type, seen in 111(95.7%) cases, followed by adenocarcinoma 3(2.6%) and squamous cell carcinoma 2(1.7%). Of the transitional cell carcinoma cases, 78(70.5%) were superficial, while 33(29.5%) were muscle invasive. Most of the transitional cell carcinoma cases 72(65%) were of lower grade (grade I and II), while 39(35%) were of grade III. CONCLUSIONS: Our hospital-based pathology experience of urinary bladder cancer was comparable with earlier studies.

Pattern of lymph node pathology in western Saudi Arabia.

BACKGROUND: This study aimed to characterize the histopathological pattern of lymph node pathology among Saudi patients and to highlight the age and gender variations of these lesions as base line data. MATERIALS AND METHODS: We retrospectively analyzed the data from lymph node biopsy specimens received at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia from January 2006 to December 2013. RESULTS: Of the 289 lymph node biopsy specimens received, 154 (53.3%) were from males and 135 (46.7%) from females giving a male: female ratio of 1.14:1. Age of the patients ranged from 2.5 to 96 years with a mean age 33.9 years. The commonest lymph node group affected was the cervical (30.4%) followed by axillary (9.7%) and inguinal (8.7%). Malignant lymphoma [71 Hodgkin's disease (HD), 57 non Hodgkin's lymphoma (NHL)] 128 (44.3%), reactive hyperplasia 68 (23.5%), and tuberculosis 41 (14.2%) were the common causes of lymph node enlargement. While HD, reactive hyperplasia and tuberculosis were commonest in young adult patients (10-29 years old) and rare above the age of 50 years; NHL was the predominant cause of lymph node enlargement above 50 years. CONCLUSIONS: Lymph node biopsy plays an important role in establishing the cause of lymphadenopathy. Among the biopsied nodes, lymphomas were the most common (44.3%) followed by non-specific reactive hyperplasia (23.5%) and tuberculous lymphadenitis (14.2%).