The Prognostic Impact of Tumor Border Configuration, Tumor Budding and Tumor Stroma Ratio in Colorectal Carcinoma.

OBJECTIVE: Tumor border configuration, tumor budding and tumor stroma ratio are reliable histopathological parameters that play a central role in the invasion-metastasis cascade. This study aimed to investigate the prognostic impact of these parameters and a new combined score in colorectal cancer. MATERIAL AND METHOD: A cohort of 103 colorectal cancer surgical specimens was retrospectively evaluated for tumor border configuration, tumor budding and tumor stroma ratio using H&E sections. A combined risk score was then constructed to divide cases into low risk-tumors and high risk-tumors. RESULTS: Infiltrating tumor border, high tumor budding, low tumor stroma ratio and high combined risk score were associated with positive lymph node involvement, presence of metastasis, high tumor grade, lymphovascular invasion, poor overall survival and short recurrence-free survival. Infiltrating tumor border, high tumor budding and high combined risk score were associated with advanced T stage. High tumor budding, and low tumor stroma ratio were associated with perineural invasion. Infiltrating tumor border was associated with increased tumor size and conventional adenocarcinoma, high tumor budding and low tumor stroma ratio. Low tumor stroma ratio was associated with high tumor budding. On multivariate survival analysis, tumor stroma ratio was found to be an independent predictor for overall survival and recurrence-free survival. CONCLUSION: Tumor border configuration, tumor budding, tumor stroma ratio and the newly constructed combined risk score are potential predictors of outcome in colorectal cancer patients, suggesting that their incorporation in the routine histopathological evaluation could be useful in determining the prognosis of colorectal cancer cases.

Role of SIX1, EYA2, and E-cadherin in ovarian carcinoma. Evidence on epithelial-mesenchymal transition from an immunohistochemical study.

This study aims to investigate the expression of SIX1, EYA2, and E-cadherin in ovarian cancer (OC). It was conducted on 97 cases of surface epithelial tumors (SEOTs). Immunohistochemistry (IHC) staining for the three markers was applied to archival paraffin-embedded sections. Results of semi-quantitative scoring were statistically compared, correlated with clinic-pathologic parameters, response to therapy and with patient survival. RESULTS: There was a significant association of SIX1 expression in the intratumoral stroma (ITS) with malignant cases (P < 0.0001). There was a significant direct correlation between tumour cell expression of SIX1 and EYA2 (P = 0.03) and an inverse correlation between SIX1 and E-cadherin (P = 0.03). Additionally, there were direct correlations between SIX1 expression and larger tumour size (P = 0.05), high mitosis (P < 0.0001), and advanced FIGO stage (P = 0.06), and between EYA2 expression and LN metastasis (P = 0.02), and low apoptotic index (P = 0.007). Only SIX1 expression in ITS affected the patient survival by univariate analysis (P = 0.004). CONCLUSIONS: SIX1/EYA2 complex may have a poor prognostic role in OC. SIX1 expression in ITS may be used as a predictive marker of stromal invasion in ovarian borderline tumors and could affect patients' survival in OC. SIX1, EYA2, and E-cadherin may constitute a pathway that could be targeted to stop the progression of SEOTs.

The Role of TROP2 in BCC and Cutaneous SCC: A Clinical and Immunohistochemical Study.

BACKGROUND: Nonmelanoma skin cancer (NMSC) mainly includes basal (BCC) and squamous (SCC) cell carcinoma. Trophoblast cell-surface antigen2 (TROP2), a cell-signal transduction, is one of the tumor-related calcium signal transducer gene family. TROP2 was highly expressed in many cancers, however, its role in BCC and SCC has not yet been studied. OBJECTIVE: To investigate TROP2 immunohistochemical expression in BCC and SCC (lesional and peri-lesional) skin compared to controls and correlates its expression with the clinicopathologic parameters of the studied cases. METHODS: This case-control study included 17 BCC and 15 SCC patients as well as 12 age and sex matched controls. History and clinical examination were completed. Histological examination of skin biopsies was done together with TROP2 immune-staining. RESULTS: In the studied BCC and SCC cases, there was a significant stepwise up-regulation of TROP2 H score from control to peri-lesional, ended by lesional epidermis in one hand (p=0.003 for BCC and p<0.001 for SCC) and tumor island in another hand (p=0.001 for BCC and p=0.003 for SCC). TROP2 expression in both BCC and SCC tumor tissues was not affected by any of the studied clinicopathological parameters of the investigated cases. CONCLUSION: TROP2 could have an important role in BCC and SCC pathogenesis. TROP2 targeting may have appraising effect in clinical application in BCC and SCC management.

The role and relationship between programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen-4 immunohistochemical expression in colorectal carcinoma patients: an impact on outcome.

BACKGROUND: Globally, colorectal carcinoma (CRC) is the third most common cancer diagnosed in both men and women. Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are immune checkpoints that induce tumour immune escape. AIM: This study aimed to evaluate the immunohistochemical expression of PD-L1 and CTLA-4 in CRC and their relationship with clinicopathological parameters and survival data. RESULT: This study included 103 CRC, 22 adenoma and 21 non-neoplastic specimens. High PD-L1 epithelial expression was in favour of CRC and high-grade dysplastic adenoma compared to normal specimens. High PD-L1 epithelial expression was associated with larger sized tumours, perforation, advanced T stage, infiltrative tumour border configuration (TBC), high tumour budding (TB) score, low tumour-stroma ratio (TSR) and absence of peritumoural lymphocytes. High PD-L1+ tumour infiltrating lymphocytes (TILs) showed an association with absence of perforation, early T stage, pushing TBC, lower TB score, high TSR and presence of peritumoural lymphocytes. High epithelial CTLA-4 expression was in favour of adenocarcinoma, high-grade dysplastic adenoma and low-grade dysplastic adenoma compared to normal specimens. High CTLA-4 epithelial score showed an association with positive lymph nodes (LNs), presence of an infiltrative TBC and absence of peritumoural lymphocytes. Low CTLA-4+ TILs showed a significant association with advanced tumour stage and increased number of positive LNs. Prolonged survival was associated with low epithelial PD-L1 and CTLA-4, high PD-L1+ TILs and high CTLA-4+ TILs. By multivariate Cox regression analysis, PD-L1+ TILs immunoreactivity score (p = 0.020) and CTLA-4+ TILs H. score (p = 0.036) were independent prognostic factors affecting overall survival among the other prognostic factors. CONCLUSION: PD-L1 and CTLA-4 expression by tumour cells could cooperate with each other in enhancing progression of CRC leading to poor patient outcome, while their expression by TILs could stand against tumour progression.

ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients.

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies in Egypt, representing about 8.7% of cancers in both sexes with more predominance in males, making identification of valuable predictive and prognostic markers, mandatory. Cullin-RING ligases (CRL) play an important role in the ubiquitination of cell cycle-related proteins or other proteins (e.g., DNA replication protein, signal transduction protein). Regulator of Cullins-1 (ROC-1) is a key subunit of CRL. P21 belongs to the family of cyclin dependent kinase inhibitors (CKIs) which regulates cell cycle by inactivating Cyclin- Dependent Kinases key regulators of the cell cycle. CAIX a highly active member of the family of carbonic anhydrases has gained much interest as a hypoxic marker. Hypoxia is a consequence of the rapid growth of many tumors, including bladder cancer, and is an important regulator of gene expression and resistance to chemotherapy and radiotherapy. Therefore the purpose of this study is to evaluate the role of ROC-1, CAIX and P21 and its relationship with the clinico-pathological features of bladder cancer in Egyptian patients. METHODS: Using the standard immunohistochemical technique, ROC-1, CAIX and P21 expression in 80 primary bladder carcinomas and 15 normal bladder specimens as control group were assessed. The bladder carcinoma cases included 50 cases with muscle invasive bladder cancer and 30 cases with non-muscle invasive bladder cancer. RESULTS: Over expression of ROC-1, CAIX and P21 in BC were significantly associated with muscularis propria invasion and high grade BC. ROC-1, CAIX and P21, showed significant inverse relationship in primary BC cases. CAIX expression was significantly higher in BC compared with controls. Regarding the survival analysis, expression of ROC-1, CAIX and P21 didn't affect the survival of BC patients. CONCLUSIONS: High expression of ROC-1, CAIX and P21 could be promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy.

Role of insulin-like growth factor-1 in skin tags: a clinical, genetic and immunohistochemical study in a sample of Egyptian patients.

Background: Skin tags (STs) are benign connective tissue neoplasms, in which insulin-like growth factor -1 (IGF-1) has a mitogenic and antiapoptotic activity. Purpose: We aimed to study for the first time, the possible role of IGF-1 (CA) 19 and rs6214 gene polymorphisms, and its tissue immunoreactivity in the pathogenesis of STs. Patients and methods: This case-control study included 40 ST patients and 20 controls. We searched for (CA) 19 single-nucleotide polymorphism (SNP) using conversional PCR and for rs6214 gene polymorphism using real-time PCR. IGF-1 tissue immunoreactivity was investigated using polyclonal IGF-1 antibody. Results: IGF-1 immunoreactivity showed significantly strong upregulation in epidermis (p=0.002) and dermal components (endothelial cells [p=0.038] and fibroblasts [p=0.004]) of excised STs than control skin. TT and CT rs6214 genotypes and its T allele were significantly associated with STs (p=0.006 and P=0.002, respectively). Also (<192 bp) and 192-194 bp (CA) 19 genotypes were significantly predominant in ST patients than controls (p=0.013). These 4 genotypes were significantly associated with development of multiple STs and epidermal IGF-1 tissue immunoreactivity in studied patients. Conclusions: IGF-1 (CA) 19 and rs6214 gene polymorphisms may contribute to a predisposition of STs in Egyptian patients, the role of which could be mediated through local upregulation of IGF-1 in cutaneous tissues.