Clinical significance of galectin-3 expression in urinary bladder carcinoma.

OBJECTIVE: To uncover the clinical significance of galectin-3 in the evolution of urinary bladder cancer by defining galectin-3 expression and examining the relationship between its expression in a group of urothelial carcinomas versus normal tissues along with clinicopathological factors. METHODS: This retrospective study included histopathological reports and archival blocks and slides of all patients with urinary bladder cancer treated at King Abdulaziz University Hospital (Jeddah, Saudi Arabia). An anti-galectin-3 monoclonal antibody was used for immunohistochemical staining of tissue microarray slides comprising 128 cases of urothelium carcinoma and 24 specimens of normal bladder mucosa. RESULTS: Galectin-3 was downregulated during transformation, with positive expression found in 50 (39%) urinary bladder neoplasms, of which 33 (66%) showed weak immunostaining. All positively-stained malignant tumor and normal bladder mucosa samples showed cytoplasmic staining; a few samples also showed nuclear staining. No correlation was noted between galectin-3 and histotype, grade, stage, muscularis propria invasion, lymph node invasion, vascular invasion, or metastasis. A Cox proportional hazards model and Kaplan-Meier survival curves did not show differences in survival on the basis of galectin-3 expression. CONCLUSION: Galectin-3 is down-regulated in bladder cancer but is not a helpful marker for the diagnosis or prognosis of urinary bladder cancer.

High COX-2 immunostaining in papillary thyroid carcinoma is associated with adverse survival outcomes.

BACKGROUND: Thyroid carcinoma is one of the most common malignancies worldwide. More than 70%-80% are papillary thyroid carcinoma (PTC). Many factors influence the PTC pathway of development such as genetic mutations, growth factors, and radiation. More biological understanding of the genetic and molecular pathways is needed in PTC to determine tumor behavior, and initial clinical assessment. OBJECTIVES: Investigate the relation of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters to assess whether immunostaining results have prognostic significance. DESIGN: Retrospective study SETTING: Pathology department, tertiary care center METHODS: Records of PTC were retrieved and tissue microarrays were constructed. Tissue sections were stained using anti-human COX-2 monoclonal antibody. Immunostaining results were recorded and analysed. MAIN OUTCOME MEASURES: Relationship of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters. SAMPLE SIZE: 139 tissue samples from 139 patients RESULTS: High versus low COX-2 immunostaining showed no significant differences for most clinicopathological parameters. However, high COX-2 immunostaining showed borderline association with tumor multifocality (P=.05), lower overall (log-rank=8.739 and P=.003), and disease-free survival (log-rank=7.033, P=.008). CONCLUSION: The study showed a positive association of high COX-2 immunostaining with lower survival outcomes in PTC. COX-2 immunostaining could be a potential prognostic factor for survival in PTC. Additional molecular and clinical investigations are needed for further understanding the molecular pathways of COX-2 in PTC and the feasibility of using inhibitors of COX-2 as adjuvant therapy along with current chemotherapy. LIMITATIONS: Relatively low number of PTC variants, and no testing of other thyroid carcinomas. CONFLICT OF INTEREST: None.

Uncommon Localization of Extrarenal Xp11.2 Translocation-associated Renal Cell Carcinoma (RCC): Case Report.

The World Health Organization has recognized Xp11.2 translocation-associated renal cell carcinoma (RCC) as a distinct neoplasm that arises within the kidney. Although many reports of extrarenal carcinoma may be found in the literature, to the best of our knowledge, Xp11 translocation-associated RCC with intact kidneys has not been documented. This report describes a multilobulated right retroperitoneal soft tissue mass (7.9×5.3×12.6 cm) of a 37-year-old man complaining of abdominal pain in the right side. The patient underwent a computed tomography-guided biopsy. Microscopic evaluation reveals a tumor with papillary and sheaths architectures with cells revealing clear to eosinophilic cytoplasm. Immunohistochemical evaluation on the biopsy reveals that the tumor is positive for PAX-8, CD10, and TFE3. It is negative for CK7, EMA, Vimentin, RCC, CK8/18, D20, CD3, PLAP, OCT4, CD30, MART-1, Inhibin, S-100, HMB-45, Desmin, SMA, and DOG-1. The diagnosis was malignant epithelioid neoplasm and the diagnosis of translocation RCC was suggested. Excision was recommended. The patient underwent right radical nephrectomy with removal of this large mass. Pathologic examination showed a large cystic and solid, nonhomogenous mass with some necrotic areas, originating from the perirenal fat between the adrenal gland and the kidney. Microscopic features showed a tumor with papillary, rhabdoid, and clear cell features. Immunohistochemical stains showed that the tumor cells positively expressed AMACR, PAX-8, CD10, RCC, and TFE3, but were negative for cytokeratins, vimentin, HMB-45, desmin, SMA, EMA, and MSA. Cytogenetic studies confirmed the diagnosis of Xp11.2 translocation-associated RCC with positive TFE3 gene rearrangement. To the best of our knowledge, this type of extrarenal tumor has never been reported.

Expression of leptin in colorectal adenocarcinoma showed significant different survival patterns associated with tumor size, lymphovascular invasion, distant metastasis, local recurrence, and relapse of disease in the western province of Saudi Arabia.

Leptin phenotype has been suggested to be a possible biomarker for the diagnosis and prognosis of different neoplasms. Nonetheless, there are conflicts among the outcomes found in several tumors, and little is proven concerning the correlation between the phenotype of leptin and its clinical significance in colorectal carcinomas. This study will describe the phenotype of leptin in colorectal adenocarcinomas, and investigate its correlation with clinicopathological factors.Two hundred and twenty eight tissue samples include 155 colorectal carcinomas, 40 adenomas, and 33 noncancerous cases were utilized in constructing tissue microarrays which have been used in the revealing of leptin expression using leptin monoclonal antibody and immunohistochemistry staining protocol.Immunoexpression of leptin was recognized in 145 (93.5%) of colorectal tumors and 56 (76.7%) cases of control group. Histotype was considerably associated with leptin phenotype (P = .000), there is up regulation in leptin expression in colorectal carcinoma cases. Significantly higher proportion of negative leptin immunostaining cases were observed in tumors which have size more than 5 cm (P = .045). Whereas, significant different survival patterns were observed in positive cases regarding tumor size, lymphovascular invasion, distant metastasis, local recurrence and relapse of disease (P-values .046, .011, .000, .013, and .001, respectively). On the other hand, positive leptin staining colorectal tumors with size <5 cm, and with no distant metastases, local recurrence, or disease relapse had significantly better survival estimates. However, leptin immunostaining did not show noteworthy associations with age, gender, differentiation, tumor location, stage, margins involvement, lymphovascular invasion, and lymph node metastasis.The current study shows up regulation in leptin expression in colorectal adenocarcinoma compared with noncancerous control cases. Thus, immunohistochemical staining of leptin in colorectal cancer could be a helpful tool in the prediction of prognosis and survival pattern of colorectal cancer with certain clinicopathological factors (tumor size, lymphovascular invasion, distant metastasis, local recurrence, and relapse of disease).

Clusterin immunoexpression is associated with early stage endometrial carcinomas.

Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184-15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression.

Does Val/Val genotype of GSTP1 enzyme affects susceptibility to colorectal cancer in Saudi Arabia?.

OBJECTIVES: Glutathione S-transferase pi (GSTP1) is a candidate enzyme that may be involved in colorectal cancer susceptibility. Polymorphism of GSTP1 gene may cause changes in expression or structure which lead to alteration in the efficiency of catalytic function of the enzyme variants, i.e., deficient detoxification of carcinogens and consequently influences coloreActal cancer development. The present report examined the possible impact of GSTP1 (Ilel05Val) polymorphism and the risk of colorectal cancer. METHODS: Samples of paraffin embedded tissues from 83 patients with colorectal cancer as well as thirty five non-cancerous colon tissues were collected from the archive of the pathology department at King Abdulaziz University in Saudi Arabia. All cancer and control samples were subjects to DNA extraction then amplification. DNA genetic analyzer from Applied Biosystems was used to sequence the product of amplification for genotypes determination. RESULTS: None of the genotypes of GSTP1 was associated with the risk of colorectal cancer development. There were no statistical differences in the frequencies of GSTP1 genotypes between colorectal cancer cases and controls. CONCLUSION: The incidence of (Val/Val) genotype in colorectal cancer cases was three folds higher than controls. This finding is not statistically significant, but it could be of clinical consequence that it may increase the risk of colorectal cancer in Saudi Arabia.

Association between GSTP1 genotypes and hormone receptor phenotype in invasive ductal carcinomas of breast.

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression. The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation between positive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2 staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors in general and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancer and control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression status and certain phenotypes of breast cancer, which may have clinical importance.

Gleason grading of prostate cancer in needle core biopsies: a comparison of general and urologic pathologists.

BACKGROUND AND OBJECTIVES: The Gleason grading of prostate carcinoma (PCa) in needle core biopsies is a major determinant used in management planning. The objective of this study was to evaluate the concordance between general pathologists Gleason grading and that of a urologic pathologist in our community. DESIGN AND SETTING: Retrospective review conducted at three tertiary care hospitals in Jeddah and Riyadh for all prostatic biopsies with carcinoma from January 2002 to January 2011. METHODS: Gleason scores assigned by the original pathologist were compared with that of the reviewing urologic pathologists. Biopsies were originally obtained and diagnosed at different referring hospitals and independent laboratories. The kappa test was used to evaluate agreement between the original and review scores. RESULTS: For 212 biopsies the exact concordance of the Gleason score assigned by the original pathologist and the reviewer was 38.7% (82/212). However, when grouped into the main four-score categories of 2-4, 5-6, 7, and 8 or greater, disagreement was noted in 88 (41.5%) biopsies; 87 were upgraded and 1 was downgraded on review. When grouped into two-score categories of low grade (≤6) and high grade (≥7), disagreement was noted in 32 (15%) of the biopsies. CONCLUSION: Gleason grade score shows that there was only slight to fair agreement between outside and review scoring (kappa=0.43). When using only low versus high grade categorization, there was good agreement (kappa=0.69). Almost all of the cases with score disagreement were upgraded on review.