Pre-eclampsia has remained an elusive disease with serious impacts on both maternal and foetal health. Two novel markers, annexin A5 (ANXA5) and apelin are currently of considerable interest. The present study aimed to determine the placental expression of ANXA5 and apelin in pre-eclamptic placentae and also to elucidate if there is any correlation between the expression of these markers and the clinical features of both, mother and neonate. The comparison between gross and histopathological features of pre-eclamptic placentae and controls was another objective.
A prospective, observational study was undertaken for one year. Placentae of pre-eclamptic patients and matched controls (matched for age, ethnic and socio-economic background) were collected along with the clinical data. Gross and histopathological analyses were done and immunohistochemical study of placental sections with ANXA5 and apelin was also undertaken.
79 pre-eclamptic patients and equal numbers of matched controls were included in the study. The difference in weight and dimensions of placentae between the pre-eclampsia group and matched controls was significant. Histopathological features noted in the pre-eclamptic placentae included decidual vasculopathy, infarction, perivillous fibrin deposition, increased syncytial knots and distal villous hypoplasia. There was a significant reduction in the expression of both ANXA5 and apelin in pre-eclamptic placentae compared to controls. Among pre-eclamptic patients, the intensity of ANXA5 and apelin expression showed a significant association with respect to neonatal resuscitation. Furthermore, the intensity of apelin showed expression a significant correlation with the requirement of sick neonatal care unit treatment.
The results of the present study suggest that both ANXA5 and apelin levels are reduced in pre-eclamptic placentae. Hence, it is recommended to further explore the impact of these markers on pregnancy outcomes by undertaking randomized controlled trials.

To investigate the expression of Ki-67, phosphohistone H-3 (PHH3), and cytokeratin 15 (CK15) proteins in the cells of the oral mucosa (OM) according to the degree of its malignant transformation.
OM biopsy specimens from 69 patients diagnosed with focal epithelial hyperplasia, intraepithelial squamous cell neoplasia, cancer in situ, and squamous cell carcinoma were examined. Tissue antigens were determined using mouse Ki-67 monoclonal antibodies, rabbit PHH3 polyclonal antibodies, and mouse CK15 monoclonal antibodies.
There was an increase in epithelial proliferative and mitotic activities in squamous cell carcinoma and a sharp decrease in the expression of CK15 in the cytoplasm in cancer in situ and squamous cell carcinoma of the OM.
The protein CK15 can be used for the differential diagnosis between high-grade dysplasia and OM epithelial malignancy at the stage of carcinoma in situ and squamous cell carcinoma.
Изучить особенности экспрессии белков Ki-67, РНН3 и цитокератина 15 в клетках слизистой оболочки рта (СОР) в зависимости от степени ее злокачественной трансформации.
Исследовали биоптаты СОР 69 пациентов с диагнозами: эпителиальная гиперплазия, плоскоклеточная внутриэпителиальная неоплазия, рак in situ и плоскоклеточный рак СОР. Тканевые антигены определяли с помощью мышиных моноклональных антител к Ki-67, кроличьих поликлональных антител к фосфогистону Н3 и мышиных моноклональных антител к цитокератину 15.
Выявлены повышение пролиферативной активности эпителия при плоскоклеточном раке и резкое снижение экспрессии цитокератина 15 в цитоплазме клеток при раке in situ и плоскоклеточном раке СОР.
Белок цитокератин 15 можно использовать для дифференциальной диагностики между дисплазией высокой степени и малигнизацией эпителия СОР на стадии рака in situ и инвазивного плоскоклеточного рака.

BACKGROUND: Pesticides are responsible for many occupational health hazards among farmers in developing countries. Chlorpyrifos (CPF) is one of the broad-spectrum organophosphorus (OP) insecticides used for agricultural, domestic and industrial purposes.
OBJECTIVE: The present study was designed to examine the effects of CPF on cardiac muscles and to evaluate the possible protective role of crocin using biochemical and histological methods with the intention to recognize the molecular tools of its probable cardioprotective effects.
METHODS: Thirty-six adult male albino rats were used in this study and were divided into 4 equal groups (9 rats each): negative control group, positive control group, CPF treated group and CPF & crocin treated group. The heart was removed for histological and immunohistochemical studies.
RESULTS: Stained sections of cardiac muscle fibers of group III with H&E revealed remarkable histological changes in the form of disorganization of the fibers with increase in the interstitial spaces between these fibers. Congested dilated blood capillaries could be observed with extravasation of the red blood cells leading to interstitial hemorrhage. Focal areas of mononuclear cellular infiltration could be seen in the interstitial tissue. A number of cardiac fibers achieved pale acidophilic vacuolated sarcoplasm while others achieved dark homogenous acidophilic sarcoplasm. Some nuclei were peripherally situated and pyknotic while others were centrally situated and encircled with halos. Apparently increased masses of collagen fibers among the cardiac muscle fibers and around the congested dilated blood vessels with the presence of focal parts of extensive collagen fiber deposition were noticed in Mallory-stained sections of group III. Strong positive immunoreactions in the endomysium and perimysium of the cardiac fibers, along with the walls of blood capillaries and in interstitial cells, could be detected in immunohistochemical staining sections of group III with vimentin antibody. Immunoreactivity to caspase 3 was higher in the sarcoplasm of the cardiac fibers of group III compared to that of control group. A highly significant decrease in the cardiac level of SOD and CAT; however, a highly significant increase in MDA level was noted between the control groups and CPF treated group. Additionally, there was a significant improvement of the chemical and histological representations of group IV, and these improvement pictures were toward the normal.
CONCLUSIONS: The study concludes that crocin can alleviate the toxic effect of chlorpyrifos caused by oxidative stress on cardiac muscle.

Pterygium is a triangle-shaped fibrovascular hyperplasia of the bulbar conjunctiva on the cornea. The purpose of this study was to analyze Proteoglycans (PGs) by Immunohistochemistry (IHC) in pterygium tissues and to compare the results with normal conjunctiva. Twenty-four patients (14 males) undergoing primary pterygium excision and 17 healthy individuals (10 males), undergoing extracapsular cataract surgery, were included. Pterygium tissues and normal conjunctiva tissues were surgically removed. The tissue sections were fixed in 2% paraformaldehyde and incubated with monoclonal antibodies against PGs anti-mouse IgG. Immunohistochemical study showed stronger expression of keratan sulfate in the stroma of the pterygium compared to normal conjunctiva. An increased expression of heparan sulfate was observed in the epithelial layer and around the pterygium vessels. On the other hand, dermatan sulfate showed an increased expression and localization not only in the sub-epithelial area of the pterygium and normal conjunctiva, yet throughout the stroma of the pterygium. The differences in the expression and localization of the studied extracellular matrix proteoglycans in the pterygium tissue compared to normal conjunctiva may explain the tissue hyperplasia, structure, and the functional properties in pterygium.

BACKGROUND: In vitro studies showed that the aryl hydrocarbon receptor (AHR) contributed to the development of cutaneous squamous cell carcinomas, but supporting clinical data are lacking.
METHODS: Immunohistochemical analysis was used to detect the expression of AHR, CYP1A1, EGFR, and Ki-67 in 10 actinic keratosis (AK) cases, 10 Bowen disease (BD) cases, 20 cutaneous squamous cell carcinoma (cSCC) cases and 20 normal skin samples. H-scores were used to assess the immunoreactivity.
RESULTS: Weak positive AHR immunoreactivity was found in all normal skin samples, while strong positive AHR immunoreactivity was found in atypical squamous proliferation (AK, BD and cSCC) cases. H-scores and the rate of strong immunostaining of the atypical squamous proliferation cases were higher than those of normal controls (p < 0.01). Nuclear expression of AHR was higher in atypical squamous proliferation cases than in normal controls (p < 0.01). H-scores and the nuclear expression rate of AHR were significantly higher in AK and BD cases than cSCC cases (p < 0.01). CYP1A1 expression was low and showed no differences among the four studied groups (p > 0.05). The H-score of AHR was positively correlated with EGFR expression (r = 0.54, p < 0.01) in atypical squamous proliferation cases but was not correlated with CYP1A1 (r = - 0.17, p = 0.295) and Ki-67 (r = - 0.48, p = 0.222) expression.
CONCLUSIONS: AHR plays a vital role in cSCC pathogenesis. The overexpression and activation of AHR are involved in the early development of skin cancers. AHR expression correlates with EGFR expression and may influence cell proliferation. AHR is a valuable therapeutic target for skin cancers.

BACKGROUND: Fatty acid synthase (FAS) is a valuable lipid enzyme involved in lipid biosynthesis and suggested to contribute in tumor carcinogenesis. Vascular endothelial growth factor (VEGF) is considered a serious angiogenic growth factor in the angiogenic pathway which is a very important in tumor growth and metastasis. Thus, inhibition of lipid biosynthesis and tumor angiogenesis can be new goals for colorectal cancer (CRC) treatment.
OBJECTIVE: The assessment of the expression of FAS and VEGF protein and the relationship between them in CRC with the clinicopathological parameters.
METHODS: The present retrospective study included 63 paraffin blocks previously diagnosed as primary cases of CRC. The slides were subjected to FAS and VEGF immunohistochemical staining using a streptavidin-biotin-peroxidase. The relationships among FAS and VEGF expression and clinicopathological parameters were statistically analyzed.
RESULTS: The expression rate of FAS was 81% and VEGF was 84.1% in the studied cases. FAS expression was significantly associated with histopathological type (p = 0.02) and grade (p = 0.04), and highly associated with lymph node metastasis and stage (p < 0.001).VEGF was significantly associated with histopathological type (p = 0.01) and tumor depth (p = 0.02); highly associated with grade, lymph node metastasis, and stage (p < 0.001). There was a positive association between FAS and VEGF expression in CRC (p < 0.001).
CONCLUSIONS: FAS and VEGF showed a highly significant expression in the studied primary CRC cases. A significant association was observed between their expressions, suggesting the involvement of FAS in tumor angiogenesis. So they constitute potential targets in cancer prevention and treatment and make FAS an attractive antiangiogenic target.

OBJECTIVE: To analyze the histological features of changes in the brain tissue after ischemic stroke.
METHODS: Brain tissue samples obtained in autopsy from 9 people died as a result of a left middle cerebral artery ischemic stroke from 3 to 7 days after admission were studied. Tissue samples were taken from 3 areas of the brain: 1) contiguous to the tissue necrotic damage site zone, 2) 5-10 cm distant from the previous one, 3) the contralateral hemisphere zone symmetrical to damage site. Samples were Nissl and hematoxylin-eosin stained. Detection of p53 protein, NSE, GFAP was performed by indirect immunoperoxidase immunohistochemistry.
RESULTS: A decrease in the total number of neurons and glial elements, their spatial redistribution, change in cell structure and their functional activity was found. The changes of the artery wall and impaired regional blood flow were detected. The more intense NSE reactivity; p53-positive neurons, reduced neuron-astrocytes distance were identified in zones 2 and 3.
CONCLUSIONS: Ischemic stroke is accompanied by severe histological changes. These changes with varying degrees of severity occur both in the areas adjacent to necrotic core, and in remote areas, and it is a substrate for neuroplasticity.
Цель исследования. Анализ гистологических особенностей изменений ткани головного мозга после развития ишемического инсульта (ИИ). Материал и методы. Изучены полученные при аутопсии образцы ткани головного мозга 9 больных, умерших вследствие ИИ в бассейне левой средней мозговой артерии в течение 3-7 сут от момента поступления в стационар. Образцы ткани забирали из трех зон головного мозга: 1-я - прилежащая непосредственно к очагу некротической ткани; 2-я - отдаленная от предыдущей на 5-10 см; 3-я - симметричная очагу ишемии области контралатерального полушария. Образцы окрашивали по Нисслю, гематоксилином и эозином. Выявление белков p53, NSE, GFAP проводили непрямым иммунопероксидазным иммуногистохимическим методом. Результаты. Обнаружили снижение общего количества нейронов и глиальных элементов, их пространственное перераспределение, изменение структуры клеток и их функциональной активности после ИИ. Наблюдали изменения сосудистой стенки артерий и нарушения регионарного кровотока. Во 2-й и 3-й зонах выявили участки более интенсивной реакции NSE; р53-позитивные нейроны, сокращение расстояния между нейронами и астроцитами. Заключение. ИИ сопровождается выраженными гистологическими изменениями, которые с разной степенью выраженности происходят как в прилежащих к очагу некроза, так и в удаленных от него участках и являются субстратом для реализации пластических реакций.

Adenosquamous carcinoma (ASC) of the tongue is an uncommon malignant oral neoplasm with mixed glandular and squamous differentiation and a propensity for aggressive clinical behavior. Here, we report a rare case of ASC of the lateral border of the tongue in a 65-year-old Japanese man. The patient was treated by radical operation and remained well for 6 months before developing metastasis of the hilar and pretracheal lymph nodes. Subsequently, the patient was treated with combined chemotherapy (nedaplatin plus docetaxel and S-1 for two cycles, intravenously) and radiotherapy. Radiation therapy of metastatic lymph nodes was performed at a total dose of 60 Gy and was delivered in 2 Gy fractions 5 days/week. The patient is currently tumor free and is being followed up carefully. This article describes a rare case of ASC of the tongue and its conventional histologic, immunohistochemical, and electron microscopic findings, together with a review of the literature. The findings provide important information to better understand the possible clinical and therapeutic approaches for this uncommon tumor of the tongue.

A woman in her 50s was referred to our department with the chief complaint of nasal congestion and pharyngeal discomfort. The patient had been diagnosed with sleep apnea at the Department of Internal Medicine, and had undergone nasal continuous positive airway pressure (nCPAP) therapy, but her response to the treatment was poor. A cystic lesion occupying the nasopharynx, which was detected by nasopharyngeal fiberscopy, computed tomography, and magnetic resonance imaging, was thought to be the cause of the nasal congestion, pharyngeal discomfort, and obstructive sleep apnea syndrome (OSAS). Consequently, the patient underwent extirpation of the lesion under general anesthesia for the purpose of obtaining a definitive diagnosis as well as for treatment of the nasopharyngeal tumor. The diagnosis of intra-adenoid cyst was eventually made based on the pathological findings, which revealed lymphoid tissue accompanied by expansion of the crypt, as well as inflammatory cell infiltration with follicular hyperplasia. After the operation, the patient reported subjective improvement of her symptoms, and began to respond to the nCPAP therapy for her sleep apnea syndrome. Nasopharyngeal cysts, in particular adult intra-adenoid cyst, are relatively rare. The outcomes of the current case indicated that the presence of a nasopharyngeal cystic disease was hampering the nCPAP treatment of refractory OSAS.

Glomerular sparing (GS) is defined as a unique growth pattern in which tumor cells replace the majority of renal tubes and overrun intact glomeruli. This phenomenon has been well recognized by pathologists as a typical infiltrative pattern and some studies suggested it was an independent risk factor. Here, we study the clinical, pathological, and immunohistochemical features of primary kidney neoplasms with glomerular sparing pattern. We searched the archives of our pathology department for nephrectomy specimens and reviewed all pathology reports from 2009-2013. We selected cases with tumor and collected clinicopathological information, focusing on re-evaluation of cases with glomerular sparing pattern. To facilitate our study we performed immunohistochemical stains of PAX-8, p63, and InI-1 on selected cases. We selected a total of 204 nephrectomy cases in this study, including 163 cases of renal cell carcinoma; 37 cases of urothelial carcinoma; 4 cases from other categories (Wilms tumor, primary diffuse large B-cell lymphoma, angiolipoma, rhabdoid tumor). Finally, we identified 7 cases of primary kidney tumors with glomerular sparing pattern: 2 cases of clear cell renal cell carcinomas (ccRCC), 1 case of collecting duct carcinoma, 2 cases of urothelial carcinoma (UC), 1 case of diffuse large B-cell lymphoma and 1 case of malignant rhabdoid tumor. The primary kidney tumors with glomerular sparing pattern are rare and incidence in our study is <4% (7/204). There is no specificity for any tumor type, but more commonly seen in high grade UC rather than RCC. It can also be seen in rare neoplasms such as collecting duct carcinoma, lymphoma and malignant rhabdoid tumor. These GS cases need to be recognized as they are often associated with high grade, high stage, large tumor size, and worse prognosis.