Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly

Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.

Thymosin ß4 expression in colorectal polyps and adenomas

OBJECTIVE: Thymosin beta 4 (Tβ4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tβ4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tβ4 immunoreactivity and the initial steps of carcinogenesis. METHODS: In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tβ4 expression by immunohistochemistry. RESULTS: Weak cytoplasmic reactivity for Tβ4 was detected in the normal colon mucosa. No reactivity for Tβ4 was found in hyperplastic and sessile serrated polyps/adenomas. Tβ4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tβ4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tβ4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tβ4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells. CONCLUSIONS: Our study shows for the first time that Tβ4 is expressed during different steps of colon carcinogenesis. The shift of Tβ4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tβ4 in colorectal carcinogenesis. However, the real meaning of Tβ4 reactivity in dysplastic intestinal epithelium remains unknown. .

An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

Cyclo-oxygenase-2 and p53 Immunoreactivity in Superficial Early Colorectal Carcinoma / 대한소화기학회지

BACKGROUND/AIMS: De novo colorectal carcinoma shows more aggressive behavior including submucosal invasiveness. Both p53 and cyclo-oxygenase-2 (COX-2) have been shown to be involved in colon carcinogenesis, progression from adenoma to carcinoma, and submucosal invasion by tumor. We performed this study to evaluate the expression of p53 and COX-2 protein in de novo carcinoma, compared with ex-adenoma carcinoma. METHODS: Twenty three flat adenomas, 19 ex-adenoma carcinomas, 6 de novo carcinomas were included in this study. The expression of p53, COX-2 and Ki-67 were examined immunohistochemically. RESULTS: Both ex- adenoma carcinomas and de novo carcinomas showed similar size and shape. Positive staining for p53 was detected in 3 of 23 (13%) flat adenomas, in 11 of 19 (57.8%) ex-adenoma carcinomas (p<0.05), and in 1 of 6 (16.6%) de novo carcinomas. Increased numbers of COX-2 positive tumor cells were observed in 1 of 23 (4.3%) flat adenomas, in 2 of 19 (10.5%) ex-adenoma carcinomas, and in 3 of 6 (50%) de novo carcinomas. COX-2 positive expression showed increased tendency in de novo carcinoma (p=0.073). There was no correlation between COX-2, p53, and Ki-67 expression. CONCLUSION: De novo carcinoma shows increased tendency of COX-2 expression, but decreased p53 expression when compared to ex-adenoma carcinoma. These immunohistochemical findings are in accordance with the fact that de novo carcinoma has no preceding adenoma, with more frequent submucosal invasion despite the small lesion size.

Clinically and biochemically silent thyrotroph adenoma with oncocytic change.

A case of clinically and biochemically silent pituitary tumour with ultrastructural and immunohistochemical evidence of thyroid stimulating hormone secretion is presented. Significance of recognition of such silent tumours is discussed.

Immunohistochemistry of thyroid carcinoma--an experience with thyroglobulin and calcitonin.

A retrospective immunohistochemical study of 33 cases of primary thyroid carcinomas and 5 cases of metastases to thyroid was carried out. The immunostaining for thyroglobulin and calcitonin was done by peroxidase-anti-peroxidase (PAP) technique. The optimum staining results were obtained by proper standardisation of the staining procedure and reagents. The sections were systematically evaluated for immunostaining intensity and distribution. The observations revealed that thyroglobulin and calcitonin could be useful as sensitive and specific histogenetic markers for follicular and parafollicular cell derived thyroid carcinomas respectively. However, there was no absolute correlation between thyroglobulin positivity and grade of differentiation. The immunostaining could not differentiate follicular adenoma from follicular carcinoma. More extensive study using other markers may be useful for better patient management.

An immunohistochemical study of the expression of p53 protein in colon cancer

A total of 471 cases of colonic adenocarcinomas and 28 cases of colonic adenomas were examined immunohistochemically to evaluate the expression of p53 protein in the light of their relationship with various prognostic factors. A monoclonal antibody, p53 DO-7, was used in the study. Two hundred and fourteen adenocarcinomas (45.5%) showed positive staining for p53, however only three of the adenomas (10.3%) were positive (P < 0.05). p53 was stained to neoplastic nuclei. Adjacent normal mucosal cells were negative. There were no significant correlations between p53 expression and prognostic parameters such as age, sex, gross configuration, modified Astler-Coller stages, microscopic tumor growth patterns, tumor depth, tumor size and lymph node involvements. However, left sided adenocarcinomas (49.3%) expressed p53 more often than right sided adenocarcinomas (35.6%) (P = 0.01). The positive rates were different according to the histologic differentiation; 45.2% in well differentiated, 51.3% in moderately well differentiated, 23.8% in poorly differentiated, and 26.5% in mucinous carcinomas (P = 0.011). The mean survival periods of the p53 positive and negative groups were 29 months and 32 months, respectively (P = 0.385). However, overall survival for patients with grade one and two positive p53 was better than those of grade three and four positive cases (P = 0.028). In conclusion, the result of this multivariate analysis suggests that immunohistochemically strong p53 protein expression (more than 30% of tumor cells) has value in estimating a prognosis for patients with colorectal adenocarcinomas.

Differentiation of follicular adenoma and carcinoma of thyroid by immunohistochemical demonstration of ceruloplasmin.

In this study, and attempt was made to differentiate between follicular neoplasms of the thyroid using an immunoperoxidase staining technique for detection of ceruloplasmin. 54 histologically proved benign and malignant thyroidal lesions were selected. The staining for ceruloplasmin was consistently positive in follicular carcinoma and negative in follicular adenoma.

Bauhinia purpurea agglutinin (BPA) binding sites in human gastrointestinal tract.

The binding of biotinylated BPA to parraffin sections of 18 normal gastrointestinal tract mucosa, 5 nonneoplastic polyps (NNP), 12 adenomas, and 59 carcinomas was studied by using avidinbiotin peroxidase complex (ABC) technique. In normal mucosa BPA appeared to bind both mucus and nonmucus glycoproteins but goblet cell mucus showed a decrease in binding and increase in binding of nonmucus glycoproteins as the cells lose their differentiation. BPA showed characteristic binding patterns in adenoma and carcinoma that differed from the pattern in normal mucosa. In normal mucosa linear binding to the apical cytoplasm in the columnar cells of the surface epithelium was observed, whereas in adenomas and carcinomas, in addition to the linear binding to the apical cytoplasm, diffuse cytoplasmic and granular deposits in the supranuclear, paranuclear or infranuclear zones were seen. Our findings suggest that BPA binding patterns in normal and neoplastic mucosa are related to the degree of cellular differentiation. In the process of malignant transformation the carbohydrate distribution undergoes progressive changes through the adenoma carcinoma sequence. These changes are related to the degree of dysplasia in adenomas and to the degree of differentiation in carcinomas.

Inmunohistoquímica y microscopia electrónica en tumores de hipófisis / Immunohistochemistry and electronic microscopy in pituitary tumors

La inmunohistoquímica y la microscopía electrónica han demostrado ser útiles en el estudio de los tumores de hipófisis, determinando el comportamiento biológico de estas neoplasias, el pronóstico y algunas pautas de tratamiento. Se estudiaron siete pacientes con tumores de hipófisis tratados quirúrgicamente a quienes se les realizó inmunohistoquímica y microscopía electrónica. Los hallazgos de laboratorio previos demostraron: tres prolactinomas por niveles elevados de prolactina, un tumor productor de ACTH, y dos tumores no productores. La inmunohistoquímica demostró positividad para prolactina en los tres prolactinomas (2 macro y 1 micro). El tumor productor de GH positivo para ella así como el tumor productor de ACTH (Síndrome de Nelson secundario a adrenalitis autoinmune). Un tumor no productor no mostró positividad para ningun marcador (celula null) y el otro evidenció postitividad para ACTH (adenoma silente): ambos macroadenomas. La microscopía electrónica demostró en 2 prolactinomas de variedad escasamente granular y en 1 densamente granular. El tumor productor de GH fue de tipo densamente granular. Uno de los no productores demostró positividad para ACTH convirtiéndolo en un adenoma silente. El adenoma productor de ACTH mostró numerosos gránulos secretorios y abundantes filamentos típicos de esta neoplasia

Ultrastructural study of mixed growth hormone & prolactin secreting pituitary adenomas.

An ultrastructural study was done on 15 mixed growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas surgically removed from acromegalic patients with hyper-prolactinaemia, in order to see whether the 2 hormones were present in the same cell or in different cells. Double labelling immunogold technique was used for simultaneous ultrastructural localization of GH and PRL. It was found that each neoplastic cell in these 15 tumours (30 to 50 cells were studied in each case) contained 4 populations of granules viz., (i) granules positive for only GH; (ii) granules positive for only PRL; (iii) granules positive for both GH and PRL; and (iv) granules negative for both GH and PRL (unlabelled). Though the relative percentage of these 4 types of granules varied from cell to cell even within the same tumour, the major population (49.9 to 96%) was constituted by the mixed granules showing labelling for both GH and PRL. Almost all the cells examined from each tumour appeared to be mammosomatotrophs. Thus, the study indicated that mammosomatotroph adenomas are perhaps more common among mixed GH and PRL--secreting pituitary adenomas than previously believed. It could be important to recognize these tumours from the therapeutic point of view.

Pituitary adenomas: immunohistochemical: study of 90 cases.

Pituitary tumors from 90 patients were investigated using immunohistochemical study and the results were correlated with clinical records. There were 32 benign prolactinomas and two malignant counterparts, 13 growth hormone positive tumors. 10 corticotropic adenomas, and 10 gonadotropic tumors. Four tumors showed positivity for both prolactin and growth hormone, one prolactin and gonadotropin. An example of mixed, luteinizing hormone, prolactin and growth hormone was observed. Additionally, there was an adenoma composed of two compartments secreting prolactin and growth hormone. One patient had a recurrent gonadotropin adenoma after surgical removal of the original prolactinoma. Fifteen tumors were negative for all hormones and most were nonfunctioning clinically. The clinicopathologic correlations were found to be good for prolactinoma, growth hormone positive tumors and for tumors producing both prolactin and growth hormones causing a combined feature of hyperprolactinemia and acromegaly.