CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Papillary renal cell carcinoma with extensive spindle cell foci: mimicker of mucinous tubular and spindle cell carcinoma

ABSTRACT Papillary renal cell carcinoma (PRCC) is the second most common renal cell carcinoma (RCC), accounting for 10-15% of cases. Mucinous tubular and spindle cell carcinoma (MTSCC), on the other hand, accounts for only 1% of renal tumors and has a more favorable prognosis compared to PRCC. We report a 75-year-old female with a left upper pole solid renal mass displaying features of both papillary renal cell carcinoma (PRCC) and mucinous tubular and spindle cell carcinoma (MTSC). In this case, a shaggy luminal surface, multiple papillations, and psammoma bodies, absence of E-cadherin expression, and strong CD10 expression favored PRCC. Both immunohistochemistry and genomic analysis are critical to diagnose and differentiate tumors that may have overlapping features accurately.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features

Abstract The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

The Localization of R-Spondin1 and R-Spondin 3 Peptides in Rat Hypothalamus: An Immunohistochemical Study / Localización de los Péptidos R-Spondin1 y R-Spondin3 en el Hipotálamo de Rata: Un Estudio Inmunohistoquímico

SUMMARY: The R-spondin protein family is a group of proteins that enhance Wnt/b-catenin signaling and have pleiotropic functions in stem cell growth and development. In the literature reviews, there is no histomorphological study showing the localization and distribution of R-spondins in different hypothalamic nuclei. For this reason, the purpose of this study was to determine the localization, distribution characteristics, and densities in the hypothalamic nuclei of neurons expressing Rspo1 and Rspo3 proteins. The free-floating brain sections of the male rats who were not exposed to any treatment were stained with the indirect immunoperoxidase method using the relevant antibodies. As a result of the immunohistochemical studies, it was determined that neurons expressing the Rspo1 protein were found in large numbers in the supraoptic nucleus (SON), the suprachiasmatic nucleus (SCh), anterior paraventricular nucleus, periventricular hypothalamic nucleus (PeV), anterior hypothalamic area, magnocellular preoptic nucleus (MCPO) and the lateral hypothalamic area (LH) from the hypothalamic nuclei, while they were localized in fewer numbers in the arcuate nucleus (ARC). Rspo3 protein expression was found in neurons localized in the hypothalamic nuclei SON, paraventricular nucleus (PVN), PeV, ARC, ventromedial nucleus (VMH), LH, anterior parvicellular nucleus, and zona inserta (ZI). In addition, neurons synthesizing both peptides were found in the cortex and hippocampus regions (H). Rspo1 and 3 proteins are expressed in hypothalamic energy homeostatic areas, thus these proteins may be involved in the regulation of food intake.

La familia de proteínas R-espondina es un grupo de proteínas que mejoran la señalización de Wnt/b-catenina y tienen funciones pleiotrópicas en el crecimiento y desarrollo de las células madre. En las revisiones de la literatura no existen estudios histomorfológicos que muestren la localización y distribución de las R-espondinas en diferentes núcleos hipotalámicos. Por esta razón, el propósito de este estudio fue determinar la localización, características de distribución y densidades en los núcleos hipotalámicos de neuronas que expresan las proteínas Rspo1 y Rspo3. Secciones de cerebro flotantes de ratas macho que no fueron expuestas a ningún tratamiento se tiñeron con el método de inmunoperoxidasa indirecta utilizando los anticuerpos pertinentes. Como resultado de los estudios inmunohistoquímicos, se determinó que las neuronas que expresan la proteína Rspo1 se encontraron en gran número en el núcleo supraóptico (SON), el núcleo supraquiasmático (SCh), el núcleo paraventricular anterior, el núcleo hipotalámico periventricular (PeV), el núcleo hipotalámico anterior área, núcleo preóptico magnocelular (MCPO) y el área hipotalámica lateral (LH) de los núcleos hipotalámicos, mientras que se localizaron en menor número en el núcleo arqueado (ARC). La expresión de la proteína Rspo3 se encontró en neuronas localizadas en los núcleos hipotalámicos SON, núcleo paraventricular (PVN), PeV, ARC, núcleo ventromedial (VMH), LH, núcleo parvicelular anterior y zona inserta (ZI). Además, se encontraron neuronas que sintetizan ambos péptidos en las regiones de la corteza y el hipocampo (H). Las proteínas Rspo1 y 3 se expresan en áreas homeostáticas de energía hipotalámicas, por lo que estas proteínas pueden estar involucradas en la regulación de la ingesta de alimentos.

Immunoexpression of HSP27 does not seem to influence the prognosis of oral tongue squamous cell carcinoma

Abstract New methods of early detection and risk assessment have been studied aiming to predict the prognosis of patients and directing a specialized treatment of the oral tongue squamous cell carcinoma (OTSCC). In this context, several molecular biomarkers have been investigated for this purpose, and, among them, the heat shock protein 27 (HSP27) can be named. The study aimed to analyze whether heat shock protein 27 (HSP27) exerts any influence on OTSCC, correlating its immunoexpression with clinicopathological parameters, and patient survival. The sample comprised 55 OTSCC cases and 20 normal oral mucosa specimens. The malignancy grading systems proposed by the WHO in 2005, Brandwein-Gensler et al., and Almangush et al. were applied in a histomorphological study. HSP27 expressions were evaluated through the Immunoreactivity Score System (IRS). Significant values were considered at p <0.05 for all statistical tests. Higher IRS results were observed for normal oral mucosa specimens when compared to OTSCC cases (p <0.001). No significant associations between HSP27 immunostaining, the analyzed clinicopathological parameters and patient survival were observed. The results of the present study indicate lower HSP27 expression in OTSCC cases compared to normal oral mucosa specimens. Thus, HSP27 expression does not seem to influence patient prognosis.

Resumo Novos métodos de detecção precoce e avaliação de risco estão sendo estudados com o intuito de predizer o prognóstico dos pacientes e direcionar um tratamento diferenciado. Neste contexto, vários biomarcadores moleculares têm sido investigados com esta finalidade, dentre eles a heat shock protein 27 (HSP27). Esta pesquisa objetivou analisar se a HSP27 exerce alguma influência nos carcinomas de células escamosas de língua oral (CCELO), correlacionando a sua imunoexpressão com parâmetros clinicopatológicos e com a sobrevida dos pacientes. A amostra foi constituída por 55 casos de CCELO e 20 espécimes de mucosa oral normal. Os sistemas de gradação de malignidade propostos pela OMS em 2005, Brandwein-Gensler et al. e Almangush et al. foram aplicados em um estudo histomorfológico. A expressão da HSP27 foi avaliada através do Sistema de Escore de Imunorreatividade (IRS). Para todos os testes estatísticos foram considerados valores significativos com p<0,05. Foi observado um maior IRS para a mucosa oral normal quando comparado aos casos de CCELO (p<0,001). Não foram encontradas associações significativas entre a imunomarcação da HSP27 com os parâmetros clinicopatológicos analisados e com a sobrevida dos pacientes. Os resultados do presente estudo indicam uma menor expressão da HSP27 nos casos de CCELO quando comparados aos espécimes de mucosa oral normal. Assim, a expressão da HSP27 parece não influenciar o prognóstico dos pacientes.

Molecular characterization and potential therapeutic roles of miR125a in HER-2 positive gastric cancer

Introduction: miR-125a-3p could have a role in gastric cancer by targeting HER2. This study aimed to investigate the expression pattern of miR-125a-3p, identify the expression level of its target gene in gastric carcinoma, and test its effect in HER-2 positive gastric carcinoma cells. Materials and Methods: The levels of miR-125a-3p in both cancer and noncancer tissues were measured by using Quantitative real-time polymerase chain in 70 gastric carcinomas. Immunohistochemical study was used to measure the expression of HER2 protein in these carcinomas. In addition, the level of expression of this miRNA is correlated to different pathological and clinical parameters. The effects of miR-125a-3p alone and in combination with 5-FU (fluorouracil) on the growth of HER2 positive (NUGC4) and HER2 negative (ECC10) gastric carcinoma cells were also analyzed by in vitro studies. Results: Most gastric cancer tissues samples showed downregulation of miR-125a-3p (84%) when compared to their noncancer tissues. Significant correlations of downregulation of miR-125a-3p with cancer recurrence and pathological staging of gastric carcinoma (P = 0. 02 and 0.02, respectively) were noted. HER2 protein expression correlated significantly and inversely with miR-125a-3p expression (P < 0.05). A reduction in cell growth rate was noted significantly in miR-125a-3p transfected gastric carcinoma cells when 5-FU was added to them in comparison to other control cells (P < 0.01). When both gastric carcinoma cell lines were transfected with miR-125a-3p, a significantly higher growth inhibition percentage in HER2 positive (NUGC4) cell line was seen in comparison to the HER2 negative (ECC10) cells (P < 0.01). Conclusion: miR-125a-3p plays a significant role in the pathogenesis of gastric carcinoma. Therapeutic transfection of miR-125a-3p in HER2 positive gastric cancer cells resulted in reduced cell proliferation and potentiate the effect of 5-FU.

Evaluation of C-X-C chemokine receptor type 4 (CXCR4) and Peroxisome proliferator-activated receptor gamma (PPAR-?) expression in colorectal carcinoma: Relation to the available clinicopathological parameters

Background: Colorectal carcinoma (CRC) is the most common malignancy of the gastrointestinal tract, representing an incredible health problem. It is essential to develop drugs against novel targets––involved in CRC tumorigenesis and progression––to improve the management of the disease. The aim of this study was to evaluate C-X-C chemokine receptor type 4 (CXCR4) and Peroxisome proliferator-activated receptor gamma (PPAR-?) expression in CRC, and to associate their expression with the available clinicopathological parameters. Materials and Methods: This study included 50 cases of primary CRC. All cases were stained by CXCR4 and PPAR-? antibodies to assess their immunohistochemical expression. The relations between their expression and clinicopathological variables were assessed. Results: CXCR4 expression was detected in 76% of studied cases. High CXCR4 expression showed significant associations with the depth of tumor invasion (P = 0.024), lymph node metastasis (P = 0.009), advanced tumor stage (P = 0.001) and the presence of vascular invasion (P = 0.035). PPAR-? expression was detected in 78% of studied cases. PPAR-? expression showed a statistically significant inverse relation with histologic types (P = 0.001), tumor grade (P = 0.005), depth of tumor invasion (P = 0.001), lymph node status (P = 0.001), TNM stage (P = 0.002), and vascular invasion (P = 0.001). Conclusions: High CXCR4 and decreased PPAR-? expressions are related to high tumor grade, advanced stage, and vascular invasion in colorectal carcinoma.

A unique coexistence of a plurihormonal pituitary adenoma with granulomatous hypophysitis

Dual pathology in the pituitary gland is a unique phenomenon. Coexistence of a pituitary adenoma with primary hypophysitis has been reported rarely with very few cases in the literature. Among the primary hypophysitis, primary granulomatous subtype has been proposed to be idiopathic and autoimmune in nature. Plurihormonal pituitary adenomas produce hormones of more than one different pituitary cell lineage. Pituitary adenoma with a single hormonal content has been documented with concurrent primary granulomatous hypophysitis. The present case describes the unique coexistence of a plurihormonal adenoma showing somatotroph, lactotroph, and corticotroph lineage with primary granulomatous inflammation in the sellar region in a 36-year-old woman.

Differential expression of “A Disintegrin and Metalloproteinase 10” in hepatocellular carcinoma and the noncancerous hepatic tissues: Contribution to HCV-promoted hepatocarcinogenesis

Background: A disintegrin and metalloproteinases (ADAMs) have emerged as therapeutic targets in many cancers. ADAM10 was particularly studied in hepatocellular carcinoma (HCC) for its potential role in hepatocarcinogenesis and HCC progression. Objective: To investigate the immunohistochemical (IHC) expression of ADAM10 in HCCs and the adjacent noncancerous tissues from 70 HCC patients, attempting to elucidate any association between ADAM10 and HCC development and/or progression. Materials and Methods: IHC staining for anti-ADAM10 was performed using horseradish peroxidase technique. An extent and intensity-dependent scoring was applied dividing samples into high- and low-expression groups. HCCs were statistically compared in relation with gender, age, cirrhosis, hepatitis C virus (HCV) status, alpha-fetoprotein (AFP) serum level, tumor size, multiplicity, encapsulation/invasion, grade, histological pattern and variant, mitosis, necrosis, vascular emboli, portal thrombosis, stage, recurrence, and mortality. Kaplan–Meier's method was used to analyze disease-free and overall survival (DFS and OS). Results: ADAM10 was expressed in 77.1% of HCCs compared with 42.9% of noncancerous tissues. Differential expression showed significant statistical difference (P = 0.02), as 38.6% of HCCs showed high expression, whereas 92.8% of noncancerous samples showed low expression. No significant differences were observed when high- and low-ADAM10 expression HCCs were compared with respect to all tested prognostic parameters except the HCV status. Patients whose tumors showed high-ADAM10 expression had relatively longer DFS and OS times, but with insignificant log-rank differences. Conclusions: ADAM10 is frequently expressed in HCCs compared with noncancerous hepatic tissues suggesting its role in hepatocarcinogenesis, especially in association with HCV. It has no association with HCC progression or survival. Further studies should be sought to investigate its validity as a therapeutic target.

Immunohistochemical detection of Treponema pallidum in skin samples with clinical and histopathological correlations and Warthin-Starry staining critical analysis

Abstract Background: Syphilis in its different phases may be a difficult diagnosis in clinical and histopathological grounds. Objectives: The present study objectives were to evaluate the detection and tissue distribution of Treponema pallidum in skin lesions of syphilis. Methods: A blinded diagnostic accuracy study was performed with immunohistochemistry and Warthin-Starry silver staining in skin samples from patients with syphilis and other diseases. Patients attended two tertiary hospitals between 2000 and 2019. Prevalence ratios (PR) and 95% confidence intervals (95% CI) were calculated for the association between immunohistochemistry positivity and clinical-histopathological variables. Results: Thirty-eight patients with syphilis and their 40 biopsy specimens were included in the study. Thirty-six skin samples were used as non-syphilis controls. The Warthin-Starry technique was unable to accurately demonstrate bacteria in all samples. Immunohistochemistry showed spirochetes only in skin samples from patients with syphilis (24/40) with 60% sensitivity (95% CI 44.8-75.2). Specificity was 100% and accuracy, 78.9% (95% CI 69.8-88.1). Most cases had spirochetes in both dermis and epidermis and there was a high bacterial load. Study limitations: Correlation between immunohistochemistry and clinical or histopathological characteristics was observed but was limited statistically due to the small sample size. Conclusions: Spirochetes were promptly seen in an immunohistochemistry protocol, which can contribute to the diagnosis of syphilis in skin biopsy samples. On the other hand, the Warthin-Starry technique showed to be of no practical value.

The association of BRAF V600E gene mutation with proliferative activity and histopathological characteristics of congenital melanocytic nevi in children

Abstract Background: A lot of congenital melanocytic nevi (CMN) carry the somatic mutation in the oncogene BRAF V600E. But the detailed histopathologic characteristics and the proliferative activity of CMN with BRAF V600E gene mutation have not been systematically documented. Objective: To identify the proliferative activity and histopathological features correlating them with BRAF V600E gene mutation status in CMN. Methods: CMN were retrospectively identified from the laboratory reporting system. Mutations were determined by Sanger sequencing. The CMN were divided into a mutant group and control group according to whether there was BRAF gene mutation and were strictly matched according to gender, age, nevus size, and location. Histopathological analysis, analysis of Ki67 expression by immunohistochemistry and laser confocal fluorescence microscopy were performed. Results: The differences in Ki67 index, the depth of nevus cell involvement and the number of nevus cell nests between the mutant group and the control group was statistically significant, with p-values of 0.041, 0.002 and 0.007, respectively. Compared with BRAFV600E negative nevi, BRAF V600E positive nevi often exhibited predominantly nested intraepidermal melanocytes, and larger junctional nests, but the difference in this datasets were not statistically significant. The number of nests (p = 0.001) was positively correlated with the proportion of Ki67 positive cells. Study limitations: A small sample of patients were included and there was no follow-up. Conclusions: BRAF V600E gene mutations were associated with high proliferative activity and distinct histopathological features in congenital melanocytic nevi.

Análisis inmunohistoquímico de MMP-1, MMP-2 y MMP-9 en ameloblastoma convencional / Immunohistochemical analysis of MMP-1, MMP-2, MMP-9 in conventional ameloblastoma

Introducción: las metaloproteinasas son enzimas que participan en la remodelación tisular y su función se relaciona con procesos fisiológicos y patológicos, como la invasión y la metástasis. El ameloblastoma convencional (AMC) es una neoplasia epitelial benigna odontogénica intraósea caracterizada por una progresión lenta y localmente invasiva, cuyo crecimiento se ha vinculado con el recambio ósea y la remodelación de la matriz extracelular. El objetivo del presente trabajo fue determinar la presencia inmunohistoquímica de MMP-1, MMP-2 y MMP-9 en el AMC. Material y métodos: se realizó un estudio piloto observacional analítico utilizando cinco muestras de AMC. Los especímenes fueron recolectados aleatoriamente del archivo del Departamento de Patología Oral y Maxilofacial, de la Escuela Nacional de Estudios Superiores (ENES) Unidad León, UNAM. Como grupo control se emplearon dos especímenes de folículo dental, obtenido de pacientes con indicación de su extracción por motivos ortodóncicos. Se realizó la técnica de inmunohistoquímica por peroxidasa, recolectando el nivel y proporción de inmunoexpresión de manera semicuantitativa. Resultados: cuatro pacientes fueron de género masculino y uno femenino, la edad promedio fue de 40.6 ± 14.9 años. Todas las muestras fueron obtenidas de la región mandibular posterior. Se observaron dos especímenes con patrón folicular y tres con plexiforme. Las MMP-2 y MMP-9 se detectaron sólo en uno de los cinco especímenes y únicamente en el parénquima de la lesión, con una proporción de 100%. Conclusión: según nuestro análisis inmunohistoquímico, las MMP-2 y MMP-9 son las metaloproteinasas que presentaron expresión positiva dentro de la patogénesis del AMC comparado a la MMP-1; no obstante, es necesario realizar este tipo de estudios en una población mayor (AU)

Introduction: metalloproteinases are enzymes involved in tissue remodeling and their function is related to physiological and pathological processes, such as invasion and metastasis. These enzymes are capable of degrading components of the extracellular matrix, which may promote tumor progression. Conventional ameloblastoma (CA) is described as a benign intraosseous epithelial odontogenic neoplasm characterized by a slow and locally invasive progression, whose growth has been linked to bone turnover and extracellular matrix remodeling. The aim of the present work was to determine the immunohistochemical presence of MMP-1, MMP-2 and MMP-9 in CA. Material and methods: an analytical observational pilot study was performed using 5 CA, randomly collected from the archive of the Department of Oral and Maxillofacial Pathology, Escuela Nacional de Estudios Superiores (ENES) Unidad León, UNAM. The control group used were two dental follicle samples, obtained from patients with extraction indication for orthodontic treatment. The peroxidase immunohistochemistry assay was performed, collecting semiquantitatively level and proportion of immunoexpression. Results: four patients were male and one female, the average age was 40.6 ± 14.9 years. All specimens were obtained from the posterior mandibular region. Two specimens were observed with follicular pattern and three with plexiform pattern. MMP-2 and MMP-9 were detected only in one of the five specimens, with presence in the parenchyma of the lesion, with a proportion of 100% of the cell analyzed. Conclusion: according to our immunohistochemical analysis, MMP-2 and MMP-9 are the metalloproteinases that presented positive expression within the pathogenesis of CA compared to MMP-1; however, it is necessary to perform this type of studies in a larger population (AU)

Fibrolamellar hepatocellular carcinoma presenting as cholestatic jaundice: An unusual presentation of a rare disease

Fibrolamellar hepatocellular carcinoma is a rare primary hepatic tumor that usually occurs in youth. The common presenting features are vague abdominal pain, nausea, vomiting and weight loss. We present a case report of a young male who presented with cholestatic jaundice and on evaluation was diagnosed to have fibrolamellar hepatocellular carcinoma. He underwent successful surgical resection of the tumor. In young individuals presenting with unexplained cholestasis, fibrolamellar hepatocellular carcinoma should be considered.

Olfactory neuroblastoma with rhabdomyoblasts: A rare case report and review of the literature

Herein we present a case of a 62-year-old male patient who was admitted with the chief complaints of nasal obstruction. The histopathological and immunohistochemical evaluation led to a diagnosis of olfactory neuroblastoma with rhabdomyoblasts. A review of the literature revealed that this is only the fourth case of olfactory neuroblastoma with rhabdomyoblasts. Thus, investigation of more cases and longer follow-up is necessary to understand the disease and identify the best treatment to improve prognosis.

Role of CD44 as cancer stem cell marker in triple-negative breast cancer and its association with histological grade and angiogenesis

Introduction: Cancer stem cells (CSC) within the tumors play a central role in tumorigenesis. It is, thus, of utmost importance to identify these cells to develop effective cancer therapy. Triple-Negative Breast Cancer (TNBC) is an aggressive molecular subtype of breast cancer associated with poor patient outcomes. The role of CD44 immunohistochemistry (IHC) as a putative CSC in breast carcinomas, particularly of the TNBC-subtype is ambiguous, with equivocal results. Aims and Objectives: The present study aims to assess the role of CSC in breast carcinoma by immunohistochemical analysis of CD44 expression in TNBC. The association of TNBC expressing CSC with histological grade as well as with angiogenesis (using CD34 IHC) has been studied. Materials and Methods: Biopsy samples from 58 patients with infiltrating ductal carcinoma, NST were studied. The histology of the tumor was sub-classified into grades 1–3. Based on immunohistochemical analysis (ER, PR, HER2/Neu), the cases were divided into TNBC and NTNBC groups. The tissue sections were also subjected to analysis for CD44 to identify the CSC-phenotype and CD34 to evaluate angiogenesis, to determine the microvascular density (MVD). Results: Out of the 58 cases in the study, 28 were TNBC and 30 were NTNBC. CSC phenotype (CD44 positive) was expressed significantly higher in the TNBC (78%) versus the NTNBC (53%) (p-value 0.043). The MVD estimated using CD34 IHC was lower in the TNBC group in our study, though the difference was not statistically significant. A larger proportion of cases in TNBC showed a higher histological grade (35%) in comparison to NTNBC (27%). However, statistically, it was not significant. Conclusion: Our study demonstrated that CD44 as a CSC marker is seen significantly more in the TNBC category of invasive ductal carcinomas. Further large-scale studies, to confirm these findings, will be of potential therapeutic and prognostic value.

Detection and evaluation of the presence of the BRAF V600E mutation in ameloblastomas in an Indian population

Introduction: Ameloblastoma is a benign epithelial odontogenic neoplasm that constitutes approximately 1% of all oral tumors and about 9 to 11% of all odontogenic tumors. They are slow-growing, locally invasive, and demonstrate a potential for metastasis and malignant transformation. The molecular pathogenesis of ameloblastoma is attributed to aberrant activity of the signal transduction pathways relating to developmental stages of odontogenesis including the mitogen-activated protein kinase (MAPK) pathway. The BRAF V600E mutation was identified as the most frequently mutated gene in this neoplasm. Studies have shown that use of BRAF inhibitors in patients diagnosed with ameloblastomas led to a significant reduction in tumor volume. Aims: To detect the expression of BRAF V600E mutation in ameloblastomas in an Indian population using immunohistochemistry. To compare the difference in the occurrence of the BRAF V600E mutation between mandibular and maxillary cases. Materials and Methods: Thirty-three formalin-fixed paraffin-embedded tissues of histopathologically proven cases of ameloblastoma were assessed for the BRAF V600E mutation by immunohistochemistry using the BRAF V600E monoclonal antibody. Patient data such as age, sex, anatomical site, recurrence were documented. Statistical Analysis: The statistical analysis was performed using the Pearson Chi-square test and Student's t-test. Results: The present study revealed a high expression of the BRAFV600E mutation in mandibular cases of ameloblastoma among Indians irrespective of the age, sex, site, recurrence or histological pattern. Conclusions: The identification of this driver mutation opens the possibility of an adjuvant therapeutic modality to reduce the significant facial disfigurement and morbidity following surgical management.

Hepatocellular carcinoma: A clinicopathological and immunohistochemical study of 116 cases from a tertiary care hospital in Southern India

Background: Diagnosis of hepatocellular carcinoma (HCC) is difficult on morphology alone in poorly differentiated tumors and metastatic carcinomas. Appropriate immunohistochemical markers are required for definite diagnosis. In this article, we have analyzed the histopathological and immunohistochemical features of HCC and elucidate the best possible immunohistochemistry (IHC) marker combination by comparing the sensitivity of various markers in different grades of tumor. Methods: A total of 116 consecutive cases were analyzed retrospectively. The hematoxylin and eosin stained sections were reviewed in all the cases. IHC was done using hepatocellular specific antigen (HSA), arginase?1, glypican?3, and polyclonal carcinoembryonic antigen (pCEA). The sensitivity of various immunohistochemical markers individually as well as in combination for different tumor grades was determined. Results: Histologically, the predominant subtype comprised of classic variant (109,93.9%) followed by combined hepatocellular and cholangiocarcinoma (4,3.4%) and fibrolamellar variant (3,2.6%). Trabecular pattern was the most common histological pattern. On grading, 65,56.03% were moderately differentiated, 34,29.31% well differentiated, and17, 14.65% poorly differentiated. HSA and polyclonal?CEA showed higher sensitivity than arginase?1 and glypican?3 in well and moderately differentiated tumors. In contrast arginase?1 and glypican?3 showed better sensitivity in poorly differentiated HCC. The overall sensitivity increased to greater than 90% if HSA/polyclonal?CEA is combined with either arginase?1/glypican?3 irrespective of tumor grade. Conclusion: Majority of the tumors were classic variants and moderately differentiated. HSA along with either arginase?1 or glypican?3 is the best combination of immunomarker for identification of hepatocellular differentiation irrespective of tumor grade.

Boon that Resolves Microscopic Puzzle

Introduction: Immunohistochemistry plays a major role to confirm the accurate diagnosis of non-Hodgkin lymphoma B cell type -Tonsillar fossa. Case Presentation: A 65 year old male presented with blocking sensation in the throat, dysphagia and loss of appetite with loss of weight since 2 months. Video laryngoscopic examination revealed a growth in the right tonsil. Contrast enhanced CT neck showed well defined mass in the tonsillar fossa with multiple enlarged lymph nodes in right submandibular and para tracheal region. Biopsy showed predominantly necrotic tonsillar tissue with lymphoid cells showing angiocentric distribution along with few bizarre cells. The differential diagnosis was Lymphoma and Poorly differentiated carcinoma. Immunohistochemistry was done which showed the neoplastic cells positive for CD 20 and negative for CD 3 and cytokeratin. A diagnosis of non-Hodgkin lymphoma B cell type-Right tonsillar fossa was made. The patient was referred to medical oncology for chemotherapy. Conclusion: We present this case to highlight the role of immunohistochemistry to arrive at the accurate diagnosis and management of the patient.

Autoimmune Diseases Affecting the Orofacial Region – An Overview

Introduction: Diseases result from abnormal divergence of the normal structural and functional well-being of an organism. It can be brought about by physical, biological, chemical, genetic, or autoimmune causes. Autoimmune diseases occur when the body’s defence system targets its own healthy cells and tissues. The clinical signs and symptoms vary depending on the target tissues. Oral lesions such as ulcers, blisters, mucositis, and gingivitis are seen in many autoimmune diseases and may be an early sign, first recognized by the dental surgeon. Objective: To review the various autoimmune diseases affecting the orofacial region and update the clinicians about their oral manifestations. Materials and Methods: Case reports, review articles and original research papers published in various electronic databases like PubMed, Cross reference, Google scholar, and data collected from books are compiled in this review article. Result and Conclusion: This review gives an overview of some of the common autoimmune diseases affecting the head and neck region, their pathogenesis, clinical features, histopathological features and laboratory findings.