Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis.

Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.

Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity.

Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas.

First insight into the effect of single oral dose therapy with artemisinin-naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection.

Praziquantel is the current drug of choice against schistosomiasis. The dependency on praziquantel exclusively is problematic, given the spread of the disease and the threat of drug resistance. This study investigates an alternative antischistosomal drug using the compound naphthoquine phosphate tablet, which is a novel single oral dose antimalarial drug, containing a combination of naphthoquine phosphate and artemisinin. In the present study, the therapeutic efficacies of different artemisinin-naphthoquine phosphate combination-dosing protocols were evaluated in experimentally infected mice harbouring juvenile or adult stages of Schistosoma mansoni (Egyptian strain). The study shows that the oral administration of artemisinin-naphthoquine phosphate combination in a single dose of 400 mg/kg on day 7 p.i. resulted in a significant worm burden reduction of 95.07%. When used at a dose of 600 mg/kg on day 21 p.i., all female worms were killed before depositing eggs, resulting in complete absence of eggs in hepatic and intestinal tissues. The same dose given on day 42 p.i. reduced total and female worm burdens by 93.36% and 94.17%, respectively. In addition, artemisinin-naphthoquine phosphate combination induced significant reductions of 80.18% and 76.73% in the hepatic and intestinal tissue egg loads, respectively. Artemisinin-naphthoquine phosphate combination also induced significant alterations in the oogram pattern with elevated levels of dead eggs. Antipathological activities were evident in the amelioration of hepatic granulomata. Our findings hold promise for the development of a novel antischistosomal drug using an artemisinin-naphthoquine phosphate combination. Further in vitro and in vivo studies should be launched to elucidate the possible mechanism/s of action and to study the effect of artemisinin-naphthoquine phosphate combination on other human schistosomes.

Expression of matrix metalloproteinase-13 and Ki-67 in nonmelanoma skin cancer in xeroderma pigmentosum and non-xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a heterogenous group of genetic diseases in which basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer (NMSC) followed by squamous cell carcinoma (SCC). The aim of this study was to investigate the expression of matrix metalloproteinase (MMP)-13 and Ki-67 in SCC and BCC from patients with and without XP to elucidate their roles in the pathogenesis of these highly aggressive tumors in patients with XP. Immunolabeling using MMP-13 and Ki-67 antibodies was performed on tissue sections derived from skin biopsies of SCC and BCC of 15 patients with XP and 40 non-XP patients. There was no significant difference between XP and non-XP patients as regards MMP-13 expression by epithelial and stromal cells of SCC or BCC. Ki-67 expression in SCC and BCC of patients with XP was significantly higher than in non-XP patients. We concluded that the higher expression of Ki-67 in NMSC of patients with XP than of non-XP patients may reflect the growth and invasive capacity of these tumors in patients with XP. MMP-13 is expressed by tumor epithelial cells, stromal and inflammatory cells of NMSC of both XP and non-XP patients.

Molecular subtypes of breast carcinoma in Egyptian women: clinicopathological features.

Breast carcinoma may be classified into distinct molecular subtypes based on immunohistochemical markers for estrogen, progesterone and Her-2/neu receptors. The aim of the study was to identify the clinicopathological features of the molecular subtypes of breast carcinoma in our locality. A total of 274 surgically resected breast carcinomas were selected from the files of the Dr. KRZ referral pathology laboratory, Mansoura, Egypt, and the Pathology Department of Mansoura University. Molecular subtypes were classified into luminal A, luminal B, Her-2/neu-expressing and triple-negative. Clinicopathological and histological features of molecular subtypes were analyzed. Luminal A subtype was the most prevalent (41.2%), followed by triple-negative subtype (28.5%), then Her2-expressing subtype (19.4%) and luminal B subtype (13.9%). The commonest histological type was infiltrating duct carcinoma (83.2%), followed by infiltrating lobular carcinoma (9.1%) and medullary carcinoma (3.2%). The luminal A subtype was significantly correlated to low tumor grade, lower number of positive lymph nodes metastasis, absence of both necrosis and syncytial growth pattern. We concluded that the commonest molecular subtype of invasive breast carcinoma among Egyptian women is luminal subtype A, which displayed favorable features. Triple-negative subtype and medullary carcinomas are present in a ratio higher than in western countries.

The use of different analgesics in orthodontic tooth movements.

OBJECTIVE: To provide a semi-quantitative assessment of the effect of different analgesics (celecoxib, ketorolac, and paracetamol) on tooth movement and bone resorption using immunohistochemical staining of matrix metalloproteinase-13 (MMP-13). MATERIALS AND METHODS: Forty white male rats (12-weeks old; body weight: 230-250 g) were divided into four groups (10 rats each) and were given the treatment once a day for 2 consecutive months. Group A (control group) rats were given the reverse osmosis water; group B rats were given 10 mg/kg celecoxib; group C rats were given 3 mg/kg ketorolac; and group D rats were given 150 mg/kg paracetamol. A precalibrated closed Sentalloy coil spring was placed inside each rat mouth to deliver a constant force of 50 cN. The magnitude of tooth movement was measured intraorally. After 2 months, the rats were sacrificed, and the sections were mounted on L-polylysine-coated glass slides. Slides from each specimen were stained with hematoxylin and eosin, and others were stained with MMP-13. Data were analyzed with the one-way analysis of variance (ANOVA). RESULTS: Celecoxib, ketorolac, and paracetamol groups showed tooth movement of 1.81 ± 0.43 mm, 1.13 ± 0.28 mm, and 1.08 ± 0.27 mm, respectively. The mean number of MMP-13-positive osteoclasts was highest in celecoxib-treated group followed by the control group and was decreased in the ketorolac and paracetamol groups. Comparing all groups to the control revealed significant differences (P < .05). CONCLUSION: Administration of celecoxib did not reduce bone resorption or interfere with tooth movement in rats compared to other analgesics tested (ketorolac and paracetamol).

Relation of CD117 immunoreactivity and microvascular density in invasive breast carcinoma.

BACKGROUND AND OBJECTIVE: In breast cancer, the expression of CD117 represents a highly controversial subject but the majority of studies have found decreased c-kit expression in malignant breast epithelium. A number of studies have reported that increased intratumoral microvessel density (MVD) is associated with poor prognosis in breast cancer. The aim of the study was to assess the relation of CD117 and MVD with other clinicopathological parameters in invasive breast carcinomas using the tissue microarray technique. MATERIALS AND METHODS: A total of 126 cases of invasive breast carcinoma of different histological types and grades were collected from files of a pathology department during 2010. Clinicopathological and histological parameters were evaluated. Sections from formalin-fixed, paraffin-embedded tumor tissues microarray blocks were immunostained with CD117 and CD34. Statistical analysis of data was done using SPSS, version 16.0. RESULTS: About 29% of invasive breast carcinomas were CD117 positive. There were significant differences between expression of CD117 in the tumor epithelial cells and age of the patient; tumor grade; tumor size, and LN metastasis. Also, there was significant relation between expression of CD117 in the tumor epithelial cells and MVD, expression of estrogen, and progesterone receptors. On multivariate analysis, the most important predictors of negativity of CD117 were tumor size and positive lymph node involvement. CONCLUSION: Lack of CD117 immunoreactivity in invasive breast carcinoma was associated with features of more aggressive tumor behavior as higher microvessel density, larger size, higher tumor grade, more lymph node metastasis, and negative estrogen and progesterone receptors.

An inexpensive method of small paraffin tissue microarrays using mechanical pencil tips.

BACKGROUND: Tissue microarray technology has provided a high throughput means of evaluating potential biomarkers in archival pathological specimens. This study was carried out in order to produce tissue microarray blocks using mechanical pencil tips without high cost. METHOD: Conventional mechanical pencil tips (Rotring Tikky II Mechanical Pencil 1.0 mm) were used to cut out 1 mm wax cylinders from the recipient block, creating from 36 to 72 holes. Three cores of tumor areas were punched out manually by using the mechanical pencil tips from donor paraffin embedded tissue blocks and transferred to the holes of the paraffin tissue microarrays. RESULTS: This technique was easy and caused little damage to the donor blocks. We successfully performed H&E slides and immunodetection without substantial tissue cylinder loss. CONCLUSION: Our mechanical pencil tip technique is the most inexpensive easy technique among the literature. It also takes a reasonable amount of time and reduces antibody consumption during immunohistochemistry.