Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence.

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. METHODS: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. RESULTS: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. CONCLUSION: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

Expression Profile of Myoepithelial Cells in DCIS: Do They Change From Protective Angels to Wicked Witches?

The mechanism of transition of ductal carcinoma in situ (DCIS) to invasive cancer is elusive but recently changes in the myoepithelial cells (MECs) have been implicated. The aim of this study is to investigate the changes in gene profile of MECs in DCIS that could compromise their tumor suppressor function leading to promotion of tumor progression. Immuno-laser capture microdissection (LCM) was used to isolate MECs from normal and DCIS breast tissues followed by whole genome expression profiling using Affymetrix HGU-133 plus2.0 arrays. The data were analyzed using Bioconductor packages then validated by using real-time quantitative polymerase chain reaction and immunohistochemistry. Ingenuity Pathways software analysis showed clustering of most of the altered genes in cancer and cell death networks, with the Wnt/B-catenin pathway as the top canonical pathway. Validation revealed a 71.4% correlation rate with the array results. Most dramatic was upregulation of Fibronectin 1 ( FN1 ) in DCIS-associated MECs. Immunohistochemistry analysis for FN1 on normal and DCIS tissues confirmed a strong correlation between FN1 protein expression by MECs and DCIS ( P <0.0001) and between high expression level and presence of invasion ( P =0.006) in DCIS. Other validated alterations in MEC expression profile included upregulation of Nephronectin and downregulation of parathyroid hormone like hormone ( PTHLH ), fibroblast growth factor receptor 2 ( FGFR2 ), ADAMTS5 , TGFBR3 , and CAV1 . In vitro experiments revealed downregulation of PTHLH in DCIS-modified MECs versus normal lines when cultured on Fibronectin matrix. This is the first study to use this in vivo technique to investigate molecular changes in MECs in DCIS. This study adds more evidences to the molecular deviations in MECs toward tumor progression in DCIS through upregulation of the tumor-promoting molecules that may lead to novel predictive and therapeutic targets.

Intralesional injection of vitamin D in verruca vulgaris increases cathelicidin (LL37) expression; therapeutic and immunohistochemical study.

INTRODUCTION: Despite the promising results of intralesional vitamin D in verruca treatment; its precise mechanism of action is not fully understood. AIM OF THE WORK: To investigate immunohistochemical expression of cathelicidin (LL 37) before and after injection of vitamin D in verruca vulgaris and to clarify its possible role in pathogenesis of verruca. PATIENTS AND METHODS: This study included 20 patients with multiple verrucae vulgaris. Vitamin D was intralesionally injected every 2 weeks for a maximum of 4 sessions or clearance of verrucae. Skin biopsies were taken from the patients before and at the end of the study and compared to skin samples from ten apparently healthy, age and sex matched individuals for histopathological and immunohistochemical assessment of LL37 expression. RESULTS: Eight (40%) verrucae showed complete response, seven (35%) showed partial response and five (25%) showed no response. Decreased epidermal thickness and reduced density of inflammatory cells in dermis were observed after injection. Significant increase in LL37 intensity of expression was observed after intralesional injection of vitamin D3 (p = .003) and in verrucae showing complete clinical response (p = .022). CONCLUSIONS: Intralesional injection of vitamin D is effective and safe treatment for verruca vulgaris and causes increase in LL37 expression.

Does involucrin have a Role in Verruca Vulgaris? A Clinical and Immunohistochemical Study.

INTRODUCTION: Several modalities are used in the treatment of verrucae vulgaris; however, their side effects are common. Vitamin D3 has been recently used as a treatment in verruca vulgaris. AIM OF THE WORK: We aimed to assess the expression of involucrin in verrucae before and after intralesional injection of vitamin D3 and its correlation with clinical response. SUBJECTS AND METHODS: This study included 60 patients with verrucae vulgaris. These patients were subjected to intralesional injection of vitamin D3 at 3-week intervals for a maximum of five sessions. The pathological assessment was done by skin biopsies obtained from thirty patients before the first session and after the last session of injection and compared to skin biopsies from 30 healthy individuals. RESULTS: The injected verrucae showed complete response in 39 patients (65%), partial response in 15 patients (25%), and no response in 6 patients (10%). Nonsmoker patients had a better response than smokers. Vitamin D3 injections also resulted in increasing involucrin expression and changing its pattern of expression. CONCLUSIONS: Intralesional vitamin D3 is an effective treatment for verrucae vulgaris. Involucrin expression is modified in verrucae.

Hepatocellular Carcinoma Score and Subclassification Into Aggressive Subtypes Using Immunohistochemical Expression of p53, ß-Catenin, CD133, and Ki-67.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy in adults. Several studies have classified HCC into molecular subtypes aiming at detecting aggressive subtypes. The aim of the present study was to investigate the role of p53, ß-catenin, CD133, and Ki-67 in subclassification of HCC into different aggressive subtypes and the correlation between those markers and the clinicopathologic characteristics of HCC patients. This retrospective study was conducted on paraffin-embedded blocks of 114 HCC specimens. Tissue microarray was constructed and immunostaining for p53, ß-catenin, CD133, and Ki-67 was performed and HCC score was formulated. P53 expression was associated with old age (P=0.028), large tumor size (P=0.019), poorly differentiated HCC (P=0.012), hepatitis B virus (HBV) positivity (P=0.032), and hepatitis C virus (HCV) negativity (P =0.046). ß-catenin expression was associated with small sized tumors (P=0.005), HBV negativity (P=0.027), early-staged tumors (P=0.029), and prolonged recurrence-free survival (P=0.045). High percentage of CD133 expression was associated with old patients (P=0.035) and HBV positivity (P= 0.045). Ki-67 expression was associated with large tumor size (P= 0.049), vascular invasion (P= 0.05), old age (P=0.035), and previous treatment of HCV by direct acting antiviral agents (P=0.005). Cases with high HCC score showed significant association with old patients (P=0.002), previous treatment of HCV by direct acting antiviral agents (P<0.001), large tumor size (P<0.001), and poorly differentiated tumors (P= 0.009). The proposed HCC score can divide HCC patients into subtypes necessitating tailoring of treatment strategy according to this proposed score to target and optimally treat the aggressive subtypes. This score needs to be further validated on large number of patients with longer follow-up period.

The Profile and Role of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: An Immunohistochemical Study.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Tumor-infiltrating lymphocytes (TILs) are a class of cells that form the tumor microenvironment and thus have an effect on carcinogenesis. The aim of this study was to investigate the immunohistochemical expression of CD8, CD4, cytotoxic T lymphocyte-associated protein-4 (CTLA-4), and granzyme B in HCC and their correlation with clinicopathologic parameters and prognosis. This study was carried out on 112 cases of HCC. High percentage of CD8+ TILs was associated with large tumors and adjacent noncirrhotic liver. High percentage of CD4+ TILs and high CD4 to CD8 ratio were associated with nonviral etiology, low alpha fetoprotein, and direct acting antiviral treatment. High percentage of CTLA-4-positive TILs tended to be associated with high-grade HCC, while a high percentage of CTLA-4 in tumor cells was associated with multiple lesions and low tumor grade. High percentage of granzyme B+ TILs was associated with low grade, early stage, and absence of tumor recurrence. High CD4 percentage and high CD4/CD8 ratio affected patients' overall survival. There is a dynamic interaction between the different subsets of lymphocytes in the environment of HCC manifested by coparallel expression of CD4 and CD8 augmenting the expression of CTLA-4, and only CD8 augments the expression of granzyme B. This opens the gate for the beneficial role of immunotherapy in the management of HCC, reducing recurrence and improving survival.

Immunohistochemical Expression of Microfibrillar-associated Protein 5 (MFAP5) in Invasive Breast Carcinoma of No Special Type.

Breast cancer (BC) remains the most prevalent female cancer in Egypt and worldwide. Microfibrillar-associated protein 5 (MFAP5) is a multifunctional glycoprotein. Although MFAP5 gene was among the genes that found globally expressed in human cancers, it had been only recently reported in few cancer research studies. This is a retrospective study that has been conducted on 66 Egyptian patients who had invasive carcinoma of no special type. Immunohistochemical staining for MFAP5 was applied on the archival formalin-fixed paraffin-embedded blocks. Staining was assessed semiquantitatively and correlated with the available clinicopathologic parameters and immunohistochemical subtypes of BC. MFAP5 epithelial cytoplasmic expression was observed in 89.4% (59/66) of cases. In contrast, nuclear expression was seen in non-neoplastic breast lobules and premalignant lesions adjacent to tumors that also exhibited constant staining in myoepithelial layer. Statistical analysis of epithelial cytoplasmic expression revealed association of MFAP5 expression with tumor size (P=0.046), high histologic grade (P=0.007), presence of lymph node metastasis (P=0.014), poor Nottingham Prognostic Index (NPI) (P=0.001), late stage (P=0.008), immunohistochemical subtypes of BC (P=0.018), and increased microvessel density using CD34 immunostianing (P=0.04). MFAP5 cytoplasmic expression was also observed in an adjacent duct carcinoma in situ component in 37/45 cases (82.2%). This study showed that MFAP5 is a novel myoepithelial cell marker that appears to be upregulated in duct epithelium in duct carcinoma in situ and invasive carcinoma of no special type during tumorogenesis and that its cytoplasmic expression in invasive tumors seems to have a poor prognostic role manifested by its association with poor prognostic parameters such as high grade, late stage, lymph node invasion, and increased microvessel density.

Intratumoral FOXP3+ Regulatory T Cells in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in Egypt and worldwide. Gene expression profiling classifies DLBCL into: germinal center B cell-like (GCB) and non germinal center B cell-like (non-GCB) DLBCL. Hans' algorithm has high concordance with gene expression profiling results. Regulatory T cells (Tregs) represent important modulators for the interaction between lymphoma cells and host microenvironment. FOXP3 is a popular single marker for Tregs. There is little information about the possible role of Tregs in high-grade lymphoma such as DLBCL. This study aims to assess the prognostic impact of FOXP3+ Tregs in DLBCL. The study was carried out on 70 archival cases (61 de novo DLBCL and 9 reactive follicular hyperplasia cases). DLBCL cases were classified into GCB and non-GCB groups using Hans' algorithm. All studied cases are subjected to FOXP3 immunostaining. Density of FOXP3+ Tregs was higher in reactive cases compared with DLBCL (P=0.000). In DLBCL cases, FOXP3 expression was associated with free spleen (P=0.02), early stage (P=0.05), centroblastic variant (P=0.003), and absence of necrosis (P=0.05). In germinal cases, density of FOXP3 was significantly higher in cases with good PS (P=0.02), very good and good revised international prognostic index (P=0.002), and low-risk age-adjusted international prognostic index >60 (P=0.01). Non germinal DLBCL cases with negative FOXP3 were significantly associated with splenic involvement (P=0.005). DLBCL cases with high FOXP3 have longer survival (P=0.03). T cells in the background of DLBCL may play a role in modulation of tumor progression. Their presence is associated with favorable prognostic parameters in DLBCL.

The Differential Immunohistochemical Expression of p53, c-Jun, c-Myc, and p21 Between HCV-related Hepatocellular Carcinoma With and Without Cirrhosis.

Hepatocellular carcinoma (HCC) constitutes 70.48% of all liver tumors among Egyptians with multifactorial etiology and complex pathogenesis. HCV infection is the most common risk factor of HCC in Egypt, which commonly develops on top of cirrhosis (HCC-C); however, 15% to 20% of HCC are reported to arise in noncirrhotic livers (HCC-NC). This study aimed to explore the differences in the immunohistochemical expression of p53, c-Jun, c-Myc, and p21 between HCC-C and HCC-NC to verify the underlying molecular pathways and to study their role in hepatocarcinogenesis. This study investigated 103 cases of HCC (86 cases of HCC-C and 17 cases HCC-NC including tumorous and nontumorous tissues) together with 10 cases of chronic hepatitis and 10 cases of pure cirrhosis as control groups. Zero, 100%, 100%, and 50% of chronic hepatitis cases were positive for p53, c-Jun, c-Myc, and p21, respectively. All cirrhotic cases were negative for p53 and c-Jun, whereas they were all positive for c-Myc and p21. A total of 41%, 11.65%, 86.4%, and 57.3% of HCC cases showed p53, c-Jun, c-Myc, and p21 expression, respectively. The only difference between HCC-C and HCC-NC was the H-score values of p21 expression, which were higher in HCC-C compared with HCC-NC (P=0.03). HCV-related HCC commonly develops on top of cirrhosis with a minority develops on top of noncirrhotic liver. Only p21 pathway appears to be upregulated in favor of HCC-C than HCC-NC. p53 is considered as a late-event molecular carcinogen, whereas p21 and c-Myc may serve as early-event molecular carcinogen in HCC. The oncogenic role of p21 may be related to its cytoplasmic localization and its promotion of c-Myc expression. Progressive increase in the intensity of c-Myc expression from chronic hepatitis to cirrhosis to HCC may refer to its role as a multistep regulator of hepatocarcinogenesis. The marked reduction of c-Jun in HCC may refer to its tumor suppressor activity.

The Prognostic Role of Ezrin and HER2/neu Expression in Osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in Egypt. Ezrin is involved in cell adhesion to the extracellular matrix and in cell-cell interactions facilitating metastasis. HER2/neu is overexpressed in breast cancer and other types of cancer. This study aimed to assess the expression of ezrin and HER2/neu in 57 primary osteosarcoma cases and to correlate their expression with the available clinicopathologic parameters and the overall, metastasis-free and event-free survival. Both ezrin and HER2/neu were not expressed in the normal bone and they were upregulated in 82.5% and 71.9% of osteosarcoma, respectively. Positive ezrin expression was significantly associated with young age (below 25 y) (P=0.01), high grade (P=0.001), and short survival time (P=0.0001). Positive HER2/neu expression was significantly associated with high-grade osteosarcoma (P=0.04). Membranous HER2/neu expression was the only factor that showed significant impact on metastasis-free (P=0.002) and event-free survival (P=0.002). Ezrin was significantly correlated with HER2/neu expression (P=0.02). Advanced stage (P=0.0001), metastasis (P=0.0001), and recurrence (P=0.01) were the factors affecting the overall survival of osteosarcoma patients. Ezrin and HER2/neu are overexpressed and coexpressed in osteosarcoma with adverse prognostic features such as high grade. Membranous pattern of HER2/neu seems to be more important than the cytoplasmic pattern because of its impact on metastasis-free and event-free survival. Therefore, ezrin and HER2/neu could be potential prognostic markers and treatment targets for osteosarcoma.

The Diagnostic Impact of C4d, CD68, and NF-κB Expression in the Differentiation Between Recurrent Hepatitis C and Acute Cellular Rejection After Liver Transplantation.

Liver transplantation is the selected treatment for patients with advanced liver disease and cirrhosis, mostly as a complication of hepatitis C virus (HCV). Recurrent HCV and acute cellular rejection (ACR) of the graft are the most common causes of graft failure. The distinction between the 2 conditions is essential because they are managed differently. In some cases, the clinical and histopathologic features may overlap between recurrent hepatitis C and ACR, making differentiation difficult. The aim of this study was to investigate the role of C4d, CD68, and nuclear factor kappa-B (NF-κB) in the differentiation between ACR and recurrent HCV in the post-liver-transplant biopsy using immunohistochemistry. C4d expression in endothelial cells of portal or central veins (P=0.001) and the number of macrophages highlighted by CD68 (P=0.02) were in favor of ACR, whereas NF-κB expression by hepatocytes was in favor of recurrent hepatitis C. Vascular injury demonstrated by endothelial expression of C4d and prominent macrophage infiltration identified by CD68 expression were the distinguishing criteria for ACR and representing humoral and cellular-mediated immunity as evoking factors for graft injury. The upregulation of NF-κB in the hepatocytes of recurrent hepatitis C could be an immune response to infection or it may be induced by HCV itself.

Immunohistochemical expression of ERα, ERß, and TFF1 in type I and II ovarian tumors.

Surface epithelial tumors of the ovary are no longer considered as a single disease but are divided into types I and II on the basis of their molecular features, cell of origin, and their behavior. A possible direct action of gonadal steroids on ovarian carcinogenesis has been suggested. The current information about the possible role of TFF1 in ovarian tumors,, together with its relationship to the estrogen receptor (ER) status, is insufficient. The aim of this study was to investigate ERα, ERß, and TFF1 expression in type I and II ovarian tumors and their correlation with clinicopathologic parameters of each type. The present study was carried out on 97 ovarian tumors [20 benign, 15 borderline, and 62 malignant (36 type I and 26 type II tumors)]. ERα expression was significantly in favor of type II tumors (P=0.04), whereas high TFF1 expression was significantly in favor of type I tumors (P=0.02). ERα and ERß showed a significant positive correlation in benign cases (P=0.004) and in type I tumors (P=0.006), but not in type II tumors. In type I tumors, the expression of ERα was correlated with serous carcinoma (P=0.002) and bilaterality (P=0.05), whereas TFF1 was correlated with mucinous carcinoma (P=0.02), unilaterality (P=0.04), early FIGO staging (P=0.01), and a low mitotic count (P=0.03). A high ERß:ERα H score ratio was associated with advanced FIGO staging in both type I (P=0.05) and type II tumors (P=0.009). The difference in the expression of ERα and TFF1 between type I and II tumors may be indicative of the difference in their origin and molecular pathway. The ERß:ERα ratio is more important in determining the net result of ER effects than the evaluation of each receptor separately, and the high ratio may promote progression to advanced stage in type I and II ovarian tumors. High TFF1 expression in ovarian mucinous carcinoma may indicate that their mucinous differentiation is toward an intestinal type rather than an endocervical type. TFF1 expression in ovarian tumors seems to occur independent of the status of the ER.

Immunohistochemical evaluation of COX-1 and COX-2 expression in keloid and hypertrophic scar.

Both keloids (KLs) and hypertrophic scars (HSs) are considered as dermal fibroproliferative diseases that differ clinically and histopathologically. Although several factors have been postulated in the etiopathogenesis of these conditions, there has been growing evidence to suggest the role of COXs in the pathogenesis of abnormal wound healing because of the reduction of formation of KL and HS in patients using nonsteroidal anti-inflammatory drugs and a COX-2 inhibitor. The aim of the present work is to evaluate the pattern and localization of COX-1 and COX-2 expression in KL and HS compared with surgical scars. COX-1 and COX-2 were analyzed on skin biopsies of 30 patients who presented with KL (15) and HS (15) and 10 normal surgical scars (controls). Both COX-1 and COX-2 were expressed not only in dermal components (fibroblasts, inflammatory cells, and endothelial cells) but also in keratinocytes of the overlying epidermis in the different studied scar lesions. The percentage of COX-1 expression increased progressively from surgical scar (40%) to HS (53.3%) to KL (100%) with a statistically significant difference (P = 0.002). COX-2 was expressed in 100% of surgical scars, 73.3% of HS and 86.7% of KL with the absence of significant differences (P > 0.05). The significant difference in COX-1 expression between HS and KL may refer to the presence of different pathways for the emergence of these diseases. The expression of COX-2 in all scars (normal or abnormal) indicates its active role as an inflammatory mediator. Keratinocytes play an active role in induction of scarring by up-regulation of inflammatory mediators, such as COX-1 and COX-2.

Immunohistochemical expression of GLUT-1 and Ki-67 in chronic plaque psoriasis.

Many inflammatory mediators and other biological markers are upregulated in psoriatic lesions; some of these alterations also persist in nonlesional skin. Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans (GLUT-1). The present study aimed at evaluating the pattern of expression of GLUT-1 and Ki-67 in psoriatic skin (involved and uninvolved) and correlating their expression with the clinicopathological parameters in the studied patients. This study was carried out on 30 patients presented with chronic plaque psoriasis and 10 apparently healthy volunteers as a control group. GLUT-1 was not expressed in epidermis of normal skin, whereas it was expressed in 76.6% of uninvolved and 86.7% of involved skin of psoriatic patients, where both the latter differed significantly regarding the intensity (P = 0.001) and localization (P = 0.001) of GLUT-1 expression. The percentage of Ki-67 expression did not differ significantly between involved and uninvolved skin of psoriatic patients, but they were higher than that of normal skin of control group. Nucleolar pattern of Ki-67 expression was significantly associated with male sex (P = 0.05), marked parakeratosis (P = 0.01), and marked angiogenesis (P = 0.05). GLUT-1 expression was associated with degree of acanthosis and percentage of Ki-67 expression. From this study, GLUT-1 is upregulated in psoriatic epidermis and may be involved in facilitation of keratinocyte proliferation in psoriasis. Nucleolar pattern of Ki-67 is an indicator of progressive keratinocyte proliferation in psoriasis.

Significance of AgNORs and ki-67 proliferative markers in differential diagnosis of thyroid lesions.

We aimed to assess the utility of quantitative analysis of AgNORs and Ki67 labeling index (LI) in the differential diagnosis of different thyroid lesions. This study included: 25 papillary carcinomas, 7 follicular carcinomas, 21 follicular adenomas and 27 nodular goiters. Using a semiautomatic image analysis system, Ag NORs parameters were measured and calculated including: total area of AgNORs, mean Ag NOR number in nuclei, nuclear area, mean area of AgNOR dots per each nucleus, number of central and marginal AgNOR dots, and the relative ratio of total area of AgNOR dots/total area of nucleus. Ki67 immunostaining was performed and the LI was determined. There was a significant difference between groups of thyroid lesions regarding total area of AgNORs, Ag NOR number and number of marginal Ag NOR dots. According to receiver operating characteristic curve, Ag NORs number =2.91 and marginal Ag NORs = 2.67 were useful cut off values above which follicular carcinoma can be diagnosed with 100 % sensitivity, 79 % specificity, 76 % PPV, 100 % NPV and 85 % diagnostic accuracy for both parameters. Mean Ki67 LI in our study was 14.12 ± 2.29, 61.42 ± 3.77, 34.90 ± 3.49 and 18.60 ± 1.96 for papillary carcinoma, follicular carcinoma, follicular adenoma and nodular goiter respectively. Ki67 LI showed statistically significant difference between follicular carcinoma and follicular adenoma (p = 0.026) and between papillary carcinoma and follicular adenoma (p = 0.007). Quantification of Ag NORs and Ki67 LI could be used as helpful ancillary methods in the differentiation between different thyroid lesions.

A case of amyloid goiter associated with intrathyroid parathyroid and lymphoepithelial cyst.

Diffuse enlargement of the thyroid gland accompanied by an interstitial tissue deposition of amyloid is a special entity termed an amyloid goiter. An amyloid goiter is a rare thyroid lesion, which has been described a long time ago. In this report, we add a new classic case of amyloid goiter that differs from other reported cases in its association with intrathyroid parathyroid and lymphoepthelial cyst involved with amyloidosis. The presence of parathyroid tissue inside the thyroid parenchyma and surrounded by amyloid material elicited a diagnostic problem due to suspected medullary carcinoma. Careful histological examination and immunohistochemical staining for parathormone and calcitonin have largely helped in the differential diagnosis. Bilaterality, diffuse, and homogeneous involvement of the thyroid gland, with absence of definite masses, all direct the diagnosis toward amyloid goiter.

Intrathyroid lymph node tissue in multinodular goiter in an Egyptian female.

We report a case of an incidental finding of intrathyroid lymph node tissue in a 40-year-old Egyptian female presenting with multinodular goiter. Collections of lymphoid tissue surrounded by capsule and mature fat cells were seen enclosed by normal thyroid follicles. Heteroplasia or deviation of the normal anatomy of the cervical lymph node groups may explain the presence of this lymphoid tissue.

Immunohistochemical evaluation of vascular endothelial growth factor (VEGF) in colorectal carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic factors over-expressed in many human cancers and is usually associated with an unfavorable outcome. This work was planned to assess VEGF and microvessel density (MVD) in colorectal carcinoma (CRC) and to correlate them with the available clinicopathological parameters. MATERIAL AND METHODS: Ten normal colonic mucosa, 21 adenoma and 70 CRC cases were examined by immunohistochemical staining using anti-VEGF antibody. RESULTS: Eighty-one percent (81%) of adenoma and 78.6% of CRC cases showed VEGF immunoreactivity; however, the intensity of staining was significantly in favour of malignant cases (p=0.032). VEGF immunostaining in CRC was correlated with low grade (p=0.009), early stage either by Dukes' system (p=0.03) or TNM stage (p=0.03), negative nodal status (p=0.04) and high mast cell count (p=0.04). MVD assessed by Haematoxylin and Eosin staining was associated with dense inflammatory response (p=0.003) and high mast cell count (p=0.006). CONCLUSIONS: VEGF could be an early carcinogenic factor in CRC that declines with its progression. Inflammatory cells including mast cells could play a role in CRC angiogenesis.

Cyclooxygenase-2 expression in chronic gastritis and gastric carcinoma, correlation with prognostic parameters.

BACKGROUND: Cyclooxygenase-2 (Cox-2) is the inducible form of cyclooxygenase enzyme. Cox-2 is induced in numerous processes such as cellular growth, differentiation, inflammation and tumorogenesis. PURPOSE: Assessment of Cox-2 expression in chronic gastritis and gastric carcinoma. MATERIAL AND METHODS: Sixteen chronic gastritis (CG) and 43 gastric carcinoma cases were subjected to an immunohistochemical approach using anti Cox-2 antibody. RESULTS: All CG cases displayed positive epithelial Cox-2 expression with only 25% positivity for stromal expression. Eighty six percent of gastric carcinoma showed epithelial Cox-2 expression that was significantly correlated with lymph node involvement (p<0.01), advanced stage (p=0.01), high microvessel density (MVD) (p=0.0001), vascular invasion (p=0.002), perineural invasion (p=0.01) and low apoptotic count (p<0.0001). Stromal Cox-2 expression was seen in 79% of gastric carcinoma cases and was significantly associated with low apoptotic count (p=0.0007), vascular invasion (p=0.001) and high microvessel density (MVD) (p=0.0003). Only stromal Cox-2 expression was significantly higher in gastric carcinoma than chronic gastritis (p=0.0001). CONCLUSIONS: Cox-2 appears to be involved in gastric carcinoma progression as it promotes angiogenesis, suppresses apoptosis and facilitates invasion and metastasis. Double expression of Cox-2 in gastric carcinoma epithelium and stroma and significant association between them demonstrate a paracrine cross effect between stromal and malignant epithelium.