IMP3 Immunohistochemical Expression in Inverted Papilloma and Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma.

Sinonasal inverted papilloma (IP) has a propensity for malignant transformation. Although the IP-associated squamous cell carcinoma (SCC) is rare, it has a poor prognosis. To the best of our knowledge, this is the first study to assess IMP3 immunohistochemical (IHC) expression in sinonasal tumors and to compare it to the Ki-67 IHC expression and to other established clinicopathological parameters. A retrospective study was conducted on three groups which consisted of 72 cases of sinonasal IP, 20 age-matched samples of normal respiratory epithelium, and 15 cases of sinonasal SCC associated with IP, which were obtained from the archives of the Pathology Lab of Ain Shams University Specialized and Ain Shams University Hospitals during the period from January 2012 to December 2019. An IHC study was performed to evaluate IMP3 and Ki-67 expression in the three groups, with correlation of IMP3 expression to established clinicopathological parameters of sinonasal SCC on top of IP. Both IMP3 and Ki-67 showed a sharp rise in expression in the sinonasal SCC group. In addition, there were statistically significant differences in expression values between the 3 groups (P = 0.001). Receiver Operating Characteristic (ROC) analysis revealed that IMP3 and Ki-67 could be used to discriminate sinonasal SCC from control and IP lesions, with sensitivity and specificity of 100% and 81.5% for IMP3, respectively, and 100% and 62.5% for Ki-67, respectively. Spearman's rho revealed that both IMP3 and Ki-67 were significantly related to the lymph node and tumor stages but not to the tumor grade. ROC analysis was performed to select cut-off scores for progression and survival for IMP3, and accordingly, Kaplan-Meier analysis showed correlation between IMP3 and overall survival, local recurrence-free survival, and metastasis-free survival in sinonasal SCC cases at the selected cut-off values. Based on our results, IMP3 could serve as a promising diagnostic, prognostic, and therapeutic marker for IP-associated sinonasal SCC.

Exploring the role CD163-labeled TAMs and FOXP3-labeled Tregs in different types of breast cancer: Reflections and putative benefits.

CONTEXT: Tumor immune microenvironment (TIME) is heterogeneous and dynamic. It exerts bimodal pro and antitumor effects. Among the TIME contributors, TAMs and Tregs are condemned as cancer cells allies rather than enemies; however, such contribution is not universally equal in all tumors. AIMS: We aimed to explore and compare TAMs and Tregs in various breast cancers and link such findings to pathologic prognostic indices. SETTINGS AND DESIGN: This was a retrospective study. METHODS AND MATERIALS: Archival blocks of 108 breast cancers were immunohistochemically studied for CD163 and FOXP3 in tumor stroma (TS) and specialized DCIS periductal stroma. FOXP3 was additionally evaluated in tumor cells. CD163 and FOXP3 expressions were compared with different histopathological prognostic categories for statistical analysis. STATISTICAL ANALYSIS USED: Analysis of data was done using the Chi-Square test. RESULTS: Both CD163+ TAM and FOXP3+ Tregs. showed statistically significant association with high tumor grade, T stage, multifocality and hormone negativity. Synchronous expression was consistent for both markers in almost all compared parameters, dual high expression of both CD163 and FOXP3 yielded additional statistically significant association with lymphovascular invasion (LVI). Periductal stromal CD163 and FOXP3 high expression showed statistically significant association with DCIS. FOXP3 tumor cells expression was similar to TS FOXP3 but additionally showed significant association with LVI and N stage; moreover, Her-2 over-expressing breast cancer was significantly associated with low FOXP3+ tumor cells. CONCLUSIONS: Breast cancer TS TAMs and Tregs. abundance reflects unfavorable prognosis in various breast cancers particularly hormone negative cancers.

Evaluation of the Potential Prognostic Value of Tumor Budding in Laryngeal Carcinoma by Conventional and Immunohistochemical Staining.

BACKGROUND: Tumor budding is a promising prognostic indicator in several cancers especially in colorectal cancer. However, only few studies have been conducted to assess and validate its prognostic value in laryngeal squamous cell carcinoma; none of which used pancytokeratin immunohistochemistry. In view of the modest results of treatment of laryngeal squamous cell carcinoma, the need of new prognostic indicators becomes of paramount importance. Aim of the Study. We aim to evaluate tumor budding in laryngeal squamous cell carcinoma, by haematoxylin and eosin, as well as by pancytokeratin immunohistochemistry. Material and Methods. A retrospective study on 118 cases of laryngeal squamous cell carcinoma from archives of Pathology Lab of Ain Shams University Specialized Hospital and Ain Shams University Hospitals from January 2014 to January 2017. The ENT and histopathology reports were reviewed to determine clinicopathologic data of the patients. RESULTS: Tumor budding shows high statistically significant relations (p = 0.0001 for each) with important clinicopathological parameters of laryngeal carcinoma (site, grade, tumor stage, lymph node stage, lymph node extracapsular invasion, and vascular invasion). The extent of tumor budding correlated with overall survival, local recurrence disease free, and distant metastasis disease free (p = 0.001 for each). Multivariate analysis showed tumor budding to be an independent prognostic factor affecting progression-free survival. There was a moderate agreement between H&E and IHC by pancytokeratin as regards detection of budding among study cases (kappa = 0.593). CONCLUSIONS: Tumor budding was correlated with poor prognostic clinicopathologic indicators in laryngeal squamous cell carcinoma. It is recommended to use pancytokeratin immunohistochemistry to evaluate tumor budding in laryngeal squamous cell carcinoma especially in confusing cases.

Diagnostic role of DOG1 and p63 immunohistochemistry in salivary gland carcinomas.

BACKGROUND: The differential diagnosis of salivary carcinomas is always difficult and challenging. Salivary neoplasms often shows more than one growth pattern and significant morphologic variability may exist within a single tumor and between different tumors. The aim of this study was to examine the role of DOG1 (discovered on gastrointestinal tumor-1) and p63 immunohistochemistry in the diagnosis and differential diagnosis of salivary carcinomas. METHODS: we examined the expression of DOG1 and p63 immunohistochemistry in 33 mucoepidermoid carcinomas (MEC), 9 acinic cell carcinomas (ACC), 10 adenoid cystic carcinomas (AdCC) and 4 myoepithelial carcinomas. RESULTS: All ACC showed strong to moderate positivity for DOG1 (P=0.001) and all were totally negative for p63. All MEC expressed strong to moderate positivity for p63 (P=0.001) while only (9.1%) were weak to moderately positive for DOG1. (80%) AdCC were moderately positive for DOG1 in ductal and myoepithelial components and (100%) showed moderate positivity for p63 in myoepithelial cells only (P=0.001). All myoepithelial carcinomas were DOG1 negative, 2 (50%) were weakly positive for p63 while the other 2 were moderately positive (P=0.5). CONCLUSION: DOG1 is a sensitive marker in the diagnosis of acinic cell carcinoma, p63 is sensitive in the diagnosis of mucoepidermoid carcinoma, the combined use of both markers is helpful and statistically significant in the differential diagnosis of acinic cell carcinoma versus mucoepidermoid carcinoma, both markers can help in the diagnosis of adenoid cystic carcinoma but they have no role in the diagnosis of myoepithelial carcinoma.

OX40/OX40L in systemic lupus erythematosus: association with disease activity and lupus nephritis.

BACKGROUND AND OBJECTIVES: OX40-OX40L interaction is implicated in the pathogenesis of systemic lupus erythematosus (SLE). We evaluated the role of OX40/OX40L as markers of disease activity and nephritis in SLE patients. DESIGN AND SETTING: Case-control study conducted in 2009 on SLE patients attending the outpatient clinics of Ain Shams University Hospital, Egypt. PATIENTS AND METHODS: We assessed the percentage of CD4+ T-lymphocytes expressing OX40 by flowcytometry, and serum OX40 ligand (OX40L) levels in 40 patients with SLE (20 with lupus nephritis and 20 without) and in 20 healthy controls. Disease activity was assessed by the University of Toronto SLE disease activity index (SLEDAI). RESULTS: The percentage of CD4+ T-lymphocytes expressing OX40 was significantly higher in SLE patients than in controls, and in patients with lupus nephritis than in those without. OX40 expression correlated positively with both serum creatinine levels and SLEDAI. OX40 expression was the highest in patients with class V lupus nephritis and lowest in class II. Serum OX40L levels were significantly higher in SLE patients than in controls, and in patients with nephritis than in those without. Serum OX40L levels correlated with serum creatinine levels but not with SLEDAI. OX40 expression on CD4+ T-cells had a higher sensitivity and specificity in diagnosing lupus nephritis than both OX40L and anti-double-stranded DNA levels. CONCLUSION: OX40-OX40L interaction plays a role in the pathogenesis of SLE. The expression of OX40 on CD4+ T-lymphocytes and the serum level of OX40L may act as markers of lupus nephritis. Measurements of percentages of CD4+ T-lymphocytes expressing OX40 may serve as an indicator of disease activity in SLE.

Immunohistochemical expression of survivin in breast carcinoma: relationship with clinicopathological parameters, proliferation and molecular classification.

BACKGROUND AND OBJECTIVE: Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinicopathological parameters, proliferation (MIB-1) and molecular classification MATERIAL AND METHODS: Our retrospective study comprised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immunostained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. RESULTS: Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immunonegative. Survivin expression showed significant association with increased tumor size (p<0.0001), high histologic grade (p=0.04), lymph node metastases (p<0.001), advanced tumor stage (p<0.0001), MIB-1 expression (p=0.02), negative estrogen receptor status (p=0.01) and negative progesterone receptor status (p<0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes (p=0.01). CONCLUSION: Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel cancer treatment. KEY WORDS: Breast carcinoma - Immunohistochemistry - MIB-1 - Molecular classification - Survivin.