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.

Comparative study of immunohistochemical expression of ERG and MAGI2 in prostatic carcinoma.

Diagnosis of Prostatic adenocarcinoma (PAC) is still a problematic issue. The objective of this study was to evaluate the diagnostic and prognostic value of ERG immunohistochemical (IHC) expression compared to MAGI2. MATERIALS AND METHODS: This study was conducted on 56 cases of PAC and 29 cases of nodular prostatic hyperplasia (NPH). IHC staining for ERG and MAGI2 was applied to archival formalin-fixed paraffin-embedded blocks. Semi-quantitative scoring was compared and correlated with clinicopathologic parameters and the Ki-67 index. RESULTS: Revealed positive ERG in 51.8% of PAC while all NPH cases were negative. On the other hand, MAGI2 was detected in 91.1% of PAC versus 17.2% of NPH. Using ROC curve, the ERG showed 53.6% sensitivity, 100% specificity, 76.5% diagnostic accuracy (DA) and area under the ROC curve 0.768 in comparison to MAGI2 that showed (91.1%, 86.2%, 88.25% and 0.948 respectively). Analysis of the combined use of the two markers revealed 95% sensitivity, 100% specificity, and 94% DA when tested synchronously. Moreover, a statistically significant inverse relationship could be detected between ERG expression and the Gleason grading group (P = 0.01) and Ki-67 index (P < 0.001). In addition, high-grade prostatic intraepithelial neoplasia (HGPIN) adjacent to carcinoma; showed positive expressions in (1/11 cases, 9.11%) for ERG and (6/11 cases, 54%) for MAGI2. CONCLUSION: This study recommends using both ERG and MAGI2 in a cocktail for better diagnostic validity of PAC. Only ERG expression could be a good prognostic indicator.

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.

The role of CK7, Ki-67, CD34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in Egyptian cholestatic neonates.

The differentiation between biliary atresia (BA) and idiopathic neonatal hepatitis (INH) is challenging with many histological overlaps especially in the first weeks of life. This study aimed to investigate the role of immunohistochemical staining of CK7, Ki67, CD34, and vimentin in addition to other clinicopathological features in the differentiation between BA and INH. Cases included 30 infants with BA and 30 infants with INH. The diagnosis was based on clinical, laboratory, and liver biopsy examination. Female gender and elevated serum gamma glutamyle transferase were in favor of BA. Portal tract changes, such as bile ductular proliferation documented by CK7, Ki67 immunostaining and angiogenesis documented by CD34 immunostaining, favored the diagnosis of BA. Copper associated protein was positive in 70% of BA cases, but not detected in INH cases. Parenchymatous changes, such as giant cell transformation and positive iron deposition and Kupffer cell proliferation documented by vimentin immunostaining, favored the diagnosis of INH.CK7, Ki67, CD34, and vimentin are helpful adjuvant immunostaining in the differentiation between BA and INH.

Immunohistochemical staining of surfactant proteins A and B in skin of psoriatic patients before and after narrow-band UVB phototherapy.

BACKGROUND: Psoriasis is a chronic inflammatory disorder that is mediated by elements of the innate and adaptive immune systems. Surfactant proteins (SPs) play an important role in host defense mechanisms. They are thought to have a potential role in some inflammatory skin diseases including psoriasis. OBJECTIVE: The aim of the study was to evaluate SP-A and SP-B immunohistochemical staining in skin of psoriatic patients before and after narrow-band UV radiation type B (NB-UVB) phototherapy. STUDY DESIGN: Immunohistochemical staining for SP-A and SP-B was performed on tissues from 20 psoriatic patients before and after NB-UVB. Results were compared with the degree of improvement assessed by the Psoriasis Area and Severity Index (PASI) and duration of treatment. RESULTS: In unaffected skin, SP-A and SP-B were restricted to the basal layer; however, in psoriatic skin, they appeared in suprabasal layers in 80% and 85% of cases, respectively. Dermal inflammatory cells showed SP-A in 11 cases (55%) and SP-B in only one case (5%). After treatment by NB-UVB, SP-A and SP-B staining showed predilection to the basal layer. Absence of SP-A staining in suprabasal layers after NB-UVB therapy was correlated to better response to therapy (p=0.003) and shorter duration of treatment (p<0.0001). CONCLUSIONS: SP-A and SP-B positivity is increased in psoriatic skin and reduced after NB-UVB therapy. Absence of SP-A in suprabasal layers after NB-UVB therapy is associated with better response and shorter duration of treatment.

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.

pS2 (TFF1) expression in prostate carcinoma: correlation with steroid receptor status.

pS2 or TFF1 is a member of the trefoil factor family, which is distributed throughout the gastrointestinal tract in both normal and diseased tissues. It is also considered to be one of the major estrogen-regulated proteins and an indicator of estrogen receptor (ER) functionality. pS2 has previously been investigated in benign and malignant prostate lesions with little information about its relationship to steroid receptor status. Our purpose was to correlate pS2 expression with steroid receptor status (ER alpha and progesterone receptor (PR)) and other pathologic variables in prostate carcinoma. 15 benign prostate hyperplasia (BPH) and 47 prostate carcinoma cases were investigated by means of immunohistochemistry for pS2, ER and PR expression. 80% of BPH showed pS2 cytoplasmic immunoreactivity in hyperplastic acini and about half of these cases also exhibited nuclear staining decorating basal or both basal and luminal nuclei. pS2 was highly expressed in prostate carcinoma (91.4%) with both cytoplasmic and nuclear patterns of staining. The latter pattern was significantly associated with carcinoma having a low Gleason score (p=0.02). pS2 lacked any significant correlation with steroid receptor status, stage or grade. Univariate survival analysis revealed a significant impact of stage (p=0.03) and nodal status (p<0.0001) on patient outcome. The diagnostic value of pS2 expression in prostate carcinoma validated 74.19% accuracy, 91.48% sensitivity and 78.18% positive predictive value. The high sensitivity of pS2 expression in prostate carcinoma could make it a suitable marker for diagnosis of prostate carcinoma, especially in metastatic cases of unknown origin. The absence of correlation and dissimilarity in immunolocalization between pS2 and ER alpha leads to the assumption that ER alpha could not be the regulatory protein for pS2 and may raise questions about the functionality of ER alpha in prostate. The nuclear pattern of pS2 immunoreactivity either in benign or malignant prostatic lesions is similar to the published data on ER beta distribution and could also identify a subset of carcinoma patients with a favorable prognosis.