Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and ß-catenin in infiltrating breast carcinoma of no special type.

BACKGROUND: KIF18A is a regulator of the cell cycle that stimulates the proliferation of cancer cells. The Wnt/ß-catenin pathway is involved in different issues' carcinogenesis and is being examined as a therapeutic target. The relationship between KIF18A and ß-catenin in breast cancer was not previously investigated. Therefore, this work aims to study the immunohistochemical expression and correlation of KIF18A and ß-catenin in breast-infiltrating duct carcinoma (IDC) and their relation to prognosis. MATERIAL AND METHODS: Slides cut from paraffin blocks of 135 IDC and 40 normal breast tissues were stained by KIF18A and ß-catenin antibodies. KIF18A cytoplasmic or nucleocytoplasmic staining and ß-catenin aberrant expression either nucleo-cytoplasmic or cytoplasmic staining were considered. RESULTS: Normal breast tissue and IDC showed a significant difference regarding KIF18A and aberrant ß-catenin expression. High KIF18A and ß-catenin H score values were associated with poor prognostic factors such as high grade, advanced stage, distant metastasis, high Ki67 status, and Her2neu-enriched subtype. There was a significant direct correlation between KIF18A and ß-catenin as regards percent and H score values. Prolonged overall survival (OS) was significantly associated with mild intensity and low H score of KIF18A, and low ß-catenin H score. CONCLUSIONS: KIF18A could be involved in breast carcinogenesis by activating ß-catenin. Overexpression of KIF18A and aberrant expression of ß-catenin are considered proto-oncogenes of breast cancer development. KIF18A and ß-catenin could be poor prognostic markers and predictors of aggressive behavior of breast cancer.

STIM1/SOX2 proteins are co-expressed in the tumor and microenvironmental stromal cells of pancreatic ductal adenocarcinoma and ampullary carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AAC) are lethal malignancies with modest benefits from surgery. SOX2 and STIM1 have been linked to anticancer activity in several human malignancies. This study included 94 tumor cases: 48 primary PDAC, 25 metastatic PDAC, and 21 primary AAC with corresponding non-tumor tissue. All cases were immunohistochemically stained for STIM1 and SOX2 and results were correlated with clinicopathologic data, patient survival, and BCL2 immunostaining results. Results revealed that STIM1 and SOX2 epithelial/stromal expressions were significantly higher in PDAC and AAC in comparison to the control groups. STIM1 and SOX2 expressions were positively correlated in the primary and metastatic PDAC (P = 0.016 and, P = 0.001, respectively). However, their expressions were not significantly associated with BCL2 expression. SOX2 epithelial/stromal expressions were positively correlated with the large tumor size in the primary AAC group (P = 0.052, P = 0.044, respectively). STIM1 stromal and SOX2 epithelial over-expressions had a bad prognostic impact on the overall survival of AAC (P = 0.002 and P = 0.001, respectively). Therefore, STIM1 and SOX2 co-expression in tumor cells and intra-tumoral stroma could contribute to the development of PDAC and AAC. STIM1/SOX2 expression is linked to a bad prognosis in AAC.

Gastric Carcinoma with low ROR alpha, low E- Cadherin and High LAPTM4B Immunohistochemical Profile; is associated with unfavorable prognosis in Egyptian patients.

In view of multiplicity of carcinogenic pathways of gastric carcinoma (GC), poor survival and chemotherapy resistance, more analysis of these pathways is required for prediction of prognosis and developing new therapeutic targets. Knocking down of RORα; induces tumor cell proliferation and epithelial-mesenchymal transition (EMT). LAPTM4B has been suggested to be associated with EMT which promote tumor invasion. This work aimed to investigate prognostic role of RORα, LAPTM4B, and E-Cadherin expression in GC. This retrospective immunohistochemical study assesses the expression of RORα, LAPTM4B, and E-Cadherin in 73 primary gastric carcinomas. Low RORα and high LAPTM4B expression in GC cases were associated with unfavorable prognostic factors such as positive lymph nodes, and high tumor budding. E-Cadherin heterogeneous staining was associated with poor prognostic criteria, such as diffuse type GC and high tumor budding. Low RORα, high LAPTM4B, and heterogeneous E-Cadherin were the most common immunohistochemical profile in GC cases. Low RORα expression showed poor prognostic impact on overall patient survival. In conclusion, RORα and LAPTM4B may have crucial role in GC aggressiveness. The predominance of low RORα, high LAPTM4B, and heterogeneous or negative E-Cadherin immunohistochemical profile in GC cases with unfavorable pathological parameters suggested that this profile may predict tumor behavior.

Expression of Friend Leukemia Integration-1 (Fli-1) and the Apoptosis Regulator B Cell Lymphoma-2 (BCL-2) in Gastric Carcinoma; an Immunohistochemical Study.

Fli-1 regulates multiple biological functions in different cancers particularly Ewing sarcoma and leukemias. There are controversial reports regarding function and prognostic significance of Fli-1 in epithelial cancer including gastric carcinoma (GC). No previous reports examined relationship between Fli-1 and BCL-2 in GC. This study aimed to investigate the expression of Fli-1 and BCL-2 in GC and expected the prognostic significance of their expression. Study was carried out on 88 gastric specimens (58 GC and 30 chronic gastritis cases). Immunohistochemical staining for Fli-1 and BCL-2 was done. There was significant lower Fli-1 and BCL-2 expression in GC than chronic gastritis. Advanced tumor stage showed significant relation with both low Fli-1 expression and negative BCL-2 expression. There was significant direct correlation between BCL-2 positivity and Fli-1 expression in GC. Cox-regression analysis showed that distant metastasis was the first independent factor affecting patients' OS. Fli-1 could act as tumor-suppressor protein involved in GC carcinogenesis. In addition, both Fli-1 and BCL-2 may be used as good prognostic markers in GC. The direct correlation between BCL-2 and Fli-1 expression could potentiate Fli-1 and BCL-2 as therapeutic targets in GC, acting together to inhibit cellular proliferation.

Fibroblast activation protein (FAP) expression in CK5/6 expressed (Basal subtype) & CK20 expressed (Luminal subtype) urothelial bladder carcinoma: an immunohistochemical study.

Urinary bladder cancer incidence varies all over the world. Egypt displays high incidence rates. Molecular subtyping helps risk stratification and personalized treatment. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment may provoke tumor-promotion or tumor suppression. Fibroblast activation protein (FAP) is a marker of CAFs, suggested to accelerate tumor progression in various cancers. In urothelial carcinoma, investigations regarding impact of FAP expression on prognosis are needed. This work aims to study impact of FAP expression in urothelial carcinoma and find its relation to CK 5/6 (basal) expressed and CK 20 (luminal) expressed immunohistochemical markers. This retrospective study included 70 urothelial carcinoma specimens. Immunohistochemistry was performed and results were analyzed. FAP was expressed in 67.1% of cases and showed significant association with advanced tumor stage, muscle invasion, mitoses in tumor cells and stratified groups; as 73.9% of FAP positive cases were of Ck5/6+/Ck20- (basal subtype). All studied parameters did not show significant association with patient's overall survival. In conclusion, FAP could have a role in modulating tumor microenvironment and promoting tumor invasion. FAP is correlated with basal subtype of urothelial carcinoma, which may be an indicator of tumor aggressiveness. FAP antagonists may be helpful in preventing tumor progression.

Expression of Transient Receptor Potential Channel of Melastatin number 8 (TRPM8) in Non- Melanoma Skin Cancer: A Clinical and Immunohistochemical study.

Transient Receptor Potential Channel of Melastatin number 8 (TRPM8) is abnormally expressed in many cancers as lung, however little is known about TRPM8 expression in non-melanoma skin cancer (NMSC) including cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). This work aimed to study TRPM8 expression in NMSC. It included 100 skin biopsies (50 normal skin as control group, 15 BCC and 35 SCC). Immunohistochemical staining for TRPM8 was done and results were correlated with clinicopathological characters. There was significant higher TRPM8 H-score in NMSC than control skin. On comparing SCC cases to control, there was significant positive TRPM8 expression, strong intensity, diffuse pattern, cytoplasmic and nucleo-cytoplasmic localization and higher range of H-score in SCC. In contrast, BCC showed significant lower TRPM8 positive expression when compared to control skin. Higher TRPM8 H-score in SCC showed significant positive correlation with large tumor size and poor tumor differentiation.TRPM8 may be implicated in pathogenesis of NMSC. Its association with bad prognostic characters; potentiates its role as prognostic biomarker and open new chances for therapeutic intervention in NMSC. TRPM8 antagonists may share in decreasing tumor growth and progression and may serve as potential target for tumor immunotherapy.

Evaluation of ASPM and TEF Gene Expressions as Potential Biomarkers for Bladder Cancer.

Bladder cancer is one of the most predominant tumors of the genitourinary tract. In addition to pathological findings, the molecular modifications that might affect tumorigenesis and tumor outcome should be considered when treating bladder cancer. Accordingly, we aimed to investigate the expression levels of both the ASPM and TEF genes in bladder cancer tissues and their value in disease prognosis. The expression levels of the ASPM and TEF genes were analyzed by quantitative real-time PCR (qRT-PCR) in 90 bladder cancer tissue specimens and 90 specimens of normal urinary bladder tissue taken away from the tumor site. The upregulation of ASPM expression and the downregulation of TEF expression were observed in bladder cancer tissues compared to adjacent normal tissues, and these levels were correlated with high-grade tumors, advanced stage disease and the presence of metastasis. Both genes had the ability to predict metastatic association with sensitivity (84.62%) and specificity (68.42%; *P < 0.001) for the ASPM gene and for the TEF gene with sensitivity (80.77%) and specificity (78.95%; *P < 0.001). Additionally, Kaplan-Meier survival analysis indicated that elevated ASPM expression levels and reduced TEF expression levels significantly correlated with decreased overall survival and progression-free survival. The current analysis concludes that ASPM and TEF expressions might be used as potential biomarkers in bladder cancer patients.

Cyclin D1 and PSA act as good prognostic and clinicopathological indicators for breast cancer.

Breast cancer is one of the main causes of malignancies in females. Many prognostic parameters are verified but they do not give sufficient data about patients' outcome. So, we must search for new prognostic and clinicopathological parameters. This study aimed to evaluate immunohistochemical expression of cyclin D1 and PSA in breast carcinoma and their relation to prognosis. It includes 79 specimens of breast invasive duct carcinoma. Overall survival time was available for all patients. There is a statistically significant association between positive PSA expression and lower tumor stage, nodal stage and tumor grade and between negative PSA expression and presence of metastasis (P value = .05, 0.01, 0.03 and 0.011, respectively). There is a highly statistically significant association between low percentage of cyclin D1 expression (<10%) and advanced tumor stage, advanced grade and presence of metastasis (P value = .002, 0.003 and 0.000, respectively) and between low and moderate percentage of Cyclin D1 expression (<10% and 10-50%) and advanced nodal stage (P value = .0.01). We concluded that Cyclin D1 and PSA were associated with good prognostic and clinicopathological parameters and therefore we suggested that they might be used as favorable prognostic indicators and should be analyzed in the context of molecular subtypes.

Plexin-B2 in psoriasis; a clinical and immunohistochemical study.

Psoriasis is an inflammatory, immune-mediated disease. Plexins are transmembrane proteins that are involved in immune system regulation and inflammation. This work aimed to investigate the immunohistochemical expression of Plexin-B2 in plaque psoriasis in both lesional and perilesional skin. This case-control study included 30 patients with psoriasis vulgaris in comparison with 20 age- and sex-matched apparently healthy persons. We used the Psoriasis Area and Severity Index (PASI) score to evaluate psoriasis severity. Biopsies from 30 lesional, 30 perilesional, and 20 control-skin patients were subjected to histopathological and immunohistochemical evaluations of Plexin-B2. There was significant stepwise overexpression of Plexin-B2 in proliferating keratinocytes from controls (66 ± 31.02) to perilesional (116 ± 41.95) and lesional (159.7 ± 63.05) skin (P < .001). Also, Plexin-B2 showed significant overexpression in dermal inflammatory cells of lesional psoriatic skin (153.67 ± 72.71) when compared to controls skin (25.71 ± 11.34) (P < .001). There was a significant positive correlation between Plexin-B2 expression and psoriasis severity (r = 0.557; P < .001). Plexin-B2 could promote skin inflammation, as well as keratinocyte proliferation in psoriasis vulgaris; therefore, it may be used as a targeted therapy for psoriasis treatment.

Evaluation of OVOL1 and Filaggrin immunohistochemical expression and clinical relevance in psoriasis.

BACKGROUND: Psoriasis is a disease of overactive immune system. OVOL1 and Filaggrin have been associated with many inflammatory skin lesions. To the best of our knowledge, the correlation between OVOL1 and Filaggrin in psoriasis was not previously investigated. This work aims to search the immunohistochemical expression and correlation between OVOL1 and Filaggrin in psoriasis. MATERIALS AND METHODS: Slides cut from paraffin blocks of 30 psoriasis cases and 30 control subjects were stained with OVOL1 and Filaggrin. Clinicopathological data were correlated with the results of staining. RESULTS: OVOL1 and Filaggrin expression in epidermis showed a significant gradual reduction from normal skin to peri-lesional and psoriasis biopsies (P < 0.001). In contrast, psoriasis dermis showed a significant overexpression of OVOL1 in inflammatory cells in relation to peri-lesional biopsies (P < 0.002). OVOL1 demonstrated a significant direct correlation with Filaggrin expression in psoriasis (r = 0.568, P < 0.004). OVOL1 and Filaggrin expression in psoriasis skin epidermis demonstrated a statistically significant negative correlation with PASI score. CONCLUSION: OVOL1 and Filaggrin might be involved in psoriasis-associated inflammation and skin hyperproliferation. OVOL1 might have a protective barrier function in the skin and could be used to stratify progressive disease. Filaggrin may play a role in progression of psoriasis. OVOL1 inhibition could be considered in suppression of Filaggrin function. OVOL1 agonists may be beneficial in psoriasis treatment.

Significance of RCC2, Rac1 and p53 Expression in Breast Infiltrating Ductal Carcinoma; An Immunohistochemical Study.

Background & Objective: The regulator of chromosome condensation 2 (RCC2) and RAS-related C3 botulinum toxin substrate 1 (Rac1) have been implicated in the promotion of breast cancer cell proliferation and migration. The signaling pathway involving p53/RCC2/Rac1 has been proposed to contribute to the regulation of colon cancer metastasis. However, until now, this pathway has not been thoroughly investigated in breast cancer. This study seeks to explore the influence of immunohistochemical expression and the correlation among RCC2, Rac1, and p53 in breast infiltrating ductal carcinoma (IDC). Methods: Immunostaining was performed on 120 breast IDC specimens using RCC2, Rac1, and p53 antibodies. Statistical analyses were conducted to examine the correlations between these antibodies. Results: A Positive expression of RCC2, Rac1, and p53 was observed in 116 (96.7%), 120 (100%), and 33 (27.5%) of the breast cancer cases, respectively. RCC2, Rac1, and p53 demonstrated association with poor prognostic parameters such as frequent mitoses, high Ki-67 status, positive lymphovascular invasion (LVI), and advanced tumor stage. A highly significant direct correlation was found between each immunohistochemical marker and the other two markers. Shorter overall survival was linked to multifocal tumors (P=0.017), advanced tumor stage (T3) (P=0.010), Luminal B subtype (P=0.015), progressive disease (P=0.003), positive Her2neu status (P=0.008), and metastasis to distant organs (P<0.001). However, RCC2, Rac1, and p53 did not exhibit a significant association with overall survival. Conclusion: The high expression levels of RCC2, Rac1, and p53 in breast IDC suggest their potential role in tumor behavior. The association of RCC2 and Rac1 with poor prognostic parameters may serve as predictive indicators for aggressive tumors, thus implying that targeted therapy could be beneficial in the treatment of breast cancer.

EpCAM, Ki67, and ESM1 Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation.

Liver transplantation (LT) is a good therapeutic decision, cures hepatocellular carcinoma (HCC) and promotes survival of cases with unrespectable HCC based on the Milan criteria. HCC still recur after LT. Identifying high risk tissue markers that predict recurrence becomes important for LT decision-making. Little is known regarding use of tissue expression of epithelial cell adhesion molecule (EpCAM) to predict HCC recurrence. This study investigates the role of EpCAM, Ki67, and endothelial-cell-specific molecule-1 (ESM1) as immunohistochemical markers to predict HCC recurrence after LT. It included 52 explanted HCC tissues from Egyptian patients who had undergone LT for HCC according to Milan criteria. Immunohistochemical staining was done on paraffin-embedded formalin-fixed tissue sections. HCC recurrence occurred in 13.5% cases. Positive EpCAM expression in HCC, was significantly associated with HCC recurrence, ( P =0.011), achieving 71.43% sensitivity, 84.44% specificity and 78.8% accuracy in predicting recurrence. High Ki67 percentage was significantly associated with HCC recurrence, ( P =0.005), achieving 57.14% sensitivity, 86.67% specificity and 82.69% accuracy in predicting HCC recurrence. ESM1 showed significant association with HCC recurrence ( P =0.041), with 71.43% sensitivity, 71.11% specificity and 71.15% accuracy in predicting HCC recurrence. EpCAM score and Ki67 percentage showed positive correlation. In conclusion, it is suggested that large tumor size (≥3 cm), advanced pathologic staging and Ki67 could be stratified as high risk predictors of HCC recurrence after LT. Although higher classes of Child-Turcotte-Pugh classification, high serum alpha-fetoprotein, microvascular invasion, positive EpCAM and ESM1 are stratified as lower risk predictors of HCC recurrence after LT.

Diagnostic role of p63 immunostaining in fine needle aspiration cytology of different breast lesions.

OBJECTIVE: To evaluate the potential diagnostic role of the myoepithelial marker p63 in fine needle aspiration cytology (FNAC) of breast in comparison to other diagnostic tools. STUDY DESIGN: A total of 49 FNAC of breast were assessed according to clinical, mammographic, cytological findings, and p63 immunostaining on FNAC. The strength of agreement with final histological diagnosis (FHD) was measured by kappa test. RESULTS: p63 was positive in myoepithelial cells of 75% (9/12) of benign cases and negative in 89% (33/37) of the malignant cases with strong agreement with the FHD (p < 0.0001, κ = 0.63). All the malignant positive cases showed variable degrees of in situ component. Only one malignant case (1/37, 0.03%) showed few p63 positive neoplastic cells in FNAC. Combined FNAC and p63 staining (with <25% cutoff point) to diagnose malignancy showed 100% sensitivity, 75% specificity, 92% positive predictive value, 100% negative predictive value, and 94% diagnostic accuracy. Most of the cytologically suspicious cases (7/9, 78%) showed negative p63 staining results, and all these suspicious cases (100%) proved to be malignant by the FHD. There was poor agreement between diagnosis according to positive background naked nuclei (NN) and the FHD (κ = 0.24 and p < 0.0001); however, presence of more than 74% positive NN is strongly suggestive of fibroadenoma. CONCLUSION: p63 immunostaining with a cutoff value of <25% to diagnose malignancy is a highly sensitive and specific myoepithelial marker which is recommended as an adjuvant tool to FNAC of breast in suspicious cases.

Role of CYR61 in psoriatic lesional and perilesional skin: A clinical and immunohistochemical study.

BACKGROUND: Psoriasis is considered as an immune-mediated disorder with significant epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (CYR61), known as CCN family member 1 (CCN1), plays an important role in cell proliferation and neovascularization which may trigger psoriasis development. AIMS: This study aimed to assess the immunostaining of CYR61 in psoriatic skin (lesional and perilesional) compared to control skin. PATIENTS/METHODS: This is a case-control study. The Psoriasis Area and Severity Index (PASI) was used to evaluate disease severity. A punch biopsy was taken from psoriatic skin lesions (30), perilesional (30) skin, and matched site of controls (20). The pathological and immunostaining assessments of CYR61 were conducted. RESULTS: There was a significant gradual progressive overexpression of CYR61 in keratinocytes from control skin to perilesional and lesional psoriatic skin (P = .00). Moreover, lesional psoriatic skin showed overexpression of CYR61 in inflammatory cells in the dermis than controls. CYR61 expression (lesional epidermis) revealed a significant positive correlation with the PASI score (r = .63; P = .00). There was a significant relationship between intensity and H-core of CYR61 in the lesional psoriatic epidermis with joint affection. CONCLUSION: CYR61 may trigger epidermal hyperplasia and potentiate inflammatory infiltration in psoriasis vulgaris patients, and therapies targeting CYR61 may be effective in the management of psoriasis vulgaris.

Smad7 in psoriasis vulgaris patients: A clinical and immunohistochemical study.

BACKGROUND: Psoriasis is an inflammatory disease that is mostly immune-derived. It causes proliferation of skin cells, forming plaques. Psoriasis etiology is unknown. It might be multifactorial. AIMS: This work aimed to study Smad7 expression in psoriasis vulgaris patients in comparison with normal skin. PATIENTS/METHODS: Thirty patients with psoriasis vulgaris in comparison with 20 age- and sex-matched seemingly healthy individuals were selected. We used psoriasis area and severity index (PASI) to evaluate psoriasis severity. Skin biopsies were prepared from skin lesions (30), perilesions (30) and control (20) groups for histopathological and immunostaining evaluation of Smad7. RESULTS: Smad7 was progressively upregulated in proliferating keratinocytes from controls (58.18 ± 30.93) to perilesional (106 ± 38.93) and lesional (156.33 ± 62.01) skin (P < .001). Also, dermal inflammatory cells showed upregulation of Smad7 expression from control skin (40 ± 28.28) to skin lesions (137.33 ± 73.86) (P < .010). Smad7 expression showed a positive significant correlation with psoriasis severity (r = .452; P < .012). CONCLUSION: Smad7 may be involved in increased keratinocyte proliferation as well as skin inflammation in psoriasis vulgaris patients.