Cytoplasm Of Adenoma Cells Research Articles

Immunohistochemical detection of prothymosin alpha in pituitary adenomas--a new marker of tumor recurrence?

Forty pituitary adenomas were immunostained with an antibody raised against the C-terminal fragment (101-109) of human prothymosin alpha (PT alpha). The strong positive immunostaining was found in the subpopulation of cell nuclei and intratumoral vessel walls, while the cytoplasm of adenoma cells was slightly immunopositive. The significantly higher percentage of PT alpha-positive cell nuclei was found in recurrent pituitary adenomas as compared with primary tumors. However, there was no correlation between the percentage of PT alpha-positive cell nuclei and Ki-67 indices. Gonadotropinomas were characterized by higher nuclear PT alpha expression in comparison to other pituitary adenomas, which is probably linked with the high recurrence rate of these tumors. It is suggested that PT alpha immunostaining may be helpful in predicting the pituitary tumor recurrence. However, this conclusion needs to be confirmed in further prospective studies. Moreover, PT alpha may be also useful as an immunohistochemical marker of the intratumoral microvasculature.

MAP-2 Expression in the Human Adenohypophysis and in Pituitary Adenomas. An Immunohistochemical Study

MAP-2, a well characterized member of the microtubule associated protein (MAP) family, binds to and stabilizes microtubules and is involved in cell proliferation as well as neuronal differentiation. The aim of the present work was to study MAP-2 expression in human adenohypophyses and pituitary adenomas. To our knowledge, data regarding MAP-2 expression in human pituitaries has not been reported to date. For immunohistochemistry, the streptavidin-biotin-peroxidase complex method was used. Nine non-tumorous adenohypophyses and 77 adenomas (GH-, PRL-, ACTH-, TSH-, FSH/LH- and/or alpha subunit- producing or immunonegative tumors) were investigated. The results show that MAP-2 is expressed in the cytoplasm of non-tumorous adenohypophysial cells as well as of various pituitary adenoma types. No significant correlation was found between MAP-2 expression and gender, patient age, mitotic activity, MIB-1 labelling indices, hormone immunoprofile, and endocrine status, ie. hormonal activity or lack thereof. Thus MAP-2 expression cannot be used to estimate cell proliferation rate, growth potential, endocrine activity or biologic behaviour of an adenoma. Immunopositivity appeared to be stronger in the cytoplasm of adenoma cells than in that of non-tumorous adenohypophysial cells, implying that the adenoma cells contain larger quantities of MAP-2. It can be concluded that the functional activity of MAP-2 is not associated with the manufacture of any specific adenohypophysial hormone(s) and is not limited to one specific cell type.

Cyclooxygenase-2 expression in colorectal adenomas.

Cyclooxygenase-2 is an important target for nonsteroidal anti-inflammatory drugs in suppressing colorectal tumorigenesis. To evaluate the role of cyclooxygenase-2 in sporadic colorectal adenoma, we correlated cyclooxygenase-2 expression in adenomas with other adenoma characteristics. Cyclooxygenase-2 expression was evaluated immunohistochemically in 95 endoscopically resected colorectal adenomas. Cyclooxygenase-2 was expressed mainly in the cytoplasm of adenoma cells, where it was seen in 74 percent (70/95) of adenomas. Expression was related significantly to grade of dysplasia (P < 0.001) and tumor size (P = 0.028). Multivariate logistic regression analysis showed cyclooxygenase-2 expression in adenoma cells to be independently associated with grade of dysplasia (P = 0.001). Observed associations suggest that cyclooxygenase-2 plays an important role in progression of the adenoma-to-carcinoma sequence.

Hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias.

The role of oncogenes in pituitary tumorigenesis remains elusive since few genetic changes have been identified so far in pituitary tumors. Pituitary tumor-transforming gene (pttg) has been recently cloned from rat GH4 pituitary tumor cells. We have previously isolated and characterized hpttg from human thymus. In the present study, we analyse the expression of hpttg mRNA in a series of human pituitary adenomas. We show that hpttg is highly expressed in the majority of pituitary adenomas while only very low levels of mRNA can be detected in normal pituitary gland by Northern blot analysis. hPTTG protein was immunolocalized mainly in the cytoplasm of adenoma cells. Other common extra-cranial malignant tumors were also analysed by immunohistochemistry. Interestingly, strong hPTTG immunoreactivity was detected in most adenocarcinomas of mammary and pulmonary origins.

Adenoma of the ampulla of Vater: putative precancerous lesion.

The histopathology of 12 patients with adenoma of the ampulla of Vater was examined to trace the adenoma-carcinoma sequence of the ampulla of Vater. Immunohistochemistry for carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 was also performed. Four large adenomas with mild dysplasia also had foci of moderate dysplasia while another one contained foci of severe dysplasia (intramucosal carcinoma). Immunohistochemically, adenomas of mild to moderate dysplasia had either linear CEA and CA19-9 immunoreactants at the apical portions, or fine granular immunoreactants in the cytoplasm of adenoma cells. In addition, adenomas of severe dysplasia (intramucosal carcinoma) showed a more diffuse or dense immunoreactivity for these two substances in the cytoplasm. These results are consistent with the adenoma-carcinoma sequence for the ampulla of Vater. The immunohistochemistry for CEA and CA19-9 was representative of the degree of dysplasia in the adenoma cells, but the relationship was not conclusive.

Grades of atypia in tubular and villous adenomas of the human colon. An electron microscopic study.

Of a total of 544 tubular, villous and tubulo-villous adenomas of the human colon which were investigated by light microscopy, six tubular and six villous adenomas were examined under the electron microscope. It was shown that the two types of adenoma differ in their tissue architecture, but not in their cytological appearance. Different grades of epithelial atypia occur in both types of adenoma. These are designated as grades I to III, correspond to mild, moderate and severe atypia respectively. Whereas adenoma cells with atypia grade I clearly show a cytological relationship with crypt epithelia of the normal colonic mucosa under the electron microscope, adenoma cells with atypia grade III have largely lost the differentiation characteristics of the parent cells and there is no longer intracytoplasmic organization. In the cytoplasm of adenoma cells with atypia grade II, glycogen storage is found as a special feature which does not occur in normal colonic epithelium. A similar finding has been described in the course of malignant transformation of the liver and kidney and thus can be regarded as a further indication of the precancerous nature of the adenomas.

Calcium deposition in human pituitary adenomas studied by histology, electron microscopy, electron diffraction and X-ray spectrometry

The incidence and morphogenesis of calcification were investigated by histology, electron microscopy, electron diffraction and X-ray spectrometry in 312 surgically removed human pituitary adenomas. By light microscopy the incidence of calcification was 9%. The calcium deposits were evident in several adenoma types, but were most frequent and extensive in prolactin-producing adenomas. Histologically calcium deposits represented amorphous precipitates and psammoma bodies staining with hematoxylin, the von Kossa technique and alizarin red. By electron microscopy, calcified deposits were noted in the cytoplasm of adenoma cells and extracellular space. Electron diffraction and X-ray spectrometry of intracellular precipitates as well as psammoma bodies showed the presence of phosphate, calcium and organically bound sulphur with a ratio of 3.5:5:2, indicating that they contained calcium hydroxyapatite. Present findings provide evidence that mitochondria with microcrystal deposition of calcium represent the primary sites of calcification.

Morphology of prolactin producing adenomas.

SUMMARYProlactin cell adenomas, not uncommonly found among tumours arising from the human pituitary gland, are regarded as representing a distinct pathological entity. They can be separated into three types: (1) densely granulated prolactin cell adenomas; (2) sparsely granulated prolactin cell adenomas; (3) mixed adenomas; consisting of prolactin cells and of growth hormone cells.By light microscopy, using conventional staining procedures, prolactin cell tumours correspond to acidophilic‐chromophobic adenomas and cannot be distinguished reliably from other adenoma types. Positive cytoplasmic staining of adenomatous prolactin cells can often be obtained by Herlant's eryfhrosin or by Brookes’carmoisine methods. Immunoperoxidase technique reveals the presence of immunoreactive prolactin in the cytoplasm of adenoma cells. By electron microscopy, densely granulated adenomatous prolactin cells closely resemble resting prolactin cells seen in the non‐tumorous pituitary. Decrease in size and number of secretory granules, proliferation of rough‐surfaced endoplasmic reticulum membranes, formation of Nebenkerns, prominence of Golgi complex, presence of misplaced exocytosis are characteristic fine structural features of sparsely granulated adenomatous prolactin cells.Although more work is required to correlate structure with secretory activity, it is justified to conclude that morphologic features of prolactin cell adenomas are sufficiently distinctive to permit their identification. Immunostaining and electron microscopy are valuable techniques revealing the cell type from which pituitary adenomas derive.

Acidophil Stem Cell Adenoma of the Human Pituitary: A New Entity

Electron microscopy and immunocytochemistry have been applied to determine the origin of 3 pituitary adenomas found among 70 surgically removed hypophysial tumors, which did not correspond to any tumor type classified so far.The tumors were surgically removed from 3 male patients between 38 - 66 years of age. Clinically, no signs indicative of hormonal hypersecretion were evident. The patients complained of decreased libido and progressing visual disturbances. Blood prolactin levels were markedly elevated in 2 cases, and were normal in one case. Blood growth hormone levels were normal. Additional endocrine laboratory tests failed to provide contributory data.By histology, the tumors corresponded to sparsely granulated acidophilicchromophobic adenomas. The cytoplasm of adenoma cells stained neither with PAS, nor with aniline blue, lead hematoxylin. Negative staining was obtained by various acid dyes, such as eosin, phloxine, orange G or light green, except for occasional granules in a few adenoma cells.